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Sample records for gliclazide

  1. Characterisation of Gliclazide-PEG 8000 Solid Dispersions

    African Journals Online (AJOL)

    Erah

    Purpose: The aim of the present study was to characterise gliclazide solid dispersions (SDs) ... Results: The solubility of gliclazide increased with increasing amount of PEG 8000 in aqueous medium. ... FTIR analysis demonstrated the absence of well-defined gliclazide - PEG 8000 .... voltage of 35 kV and 20 mA current. The.

  2. Gliclazide directly inhibits arginine-induced glucagon release

    DEFF Research Database (Denmark)

    Cejvan, Kenan; Coy, David H; Holst, Jens Juul

    2002-01-01

    Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of glicl......Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect....... In islet perifusions with DC-41-33, arginine-induced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell....

  3. Controlled porosity solubility modulated osmotic pump tablets of gliclazide.

    Science.gov (United States)

    Banerjee, Arti; Verma, P R P; Gore, Subhash

    2015-06-01

    A system that can deliver drug at a controlled rate is very important for the treatment of various chronic diseases such as diabetes, asthma, and heart disease. Poorly water-soluble drug with pH-dependent solubility such as gliclazide (GLZ) offers challenges in the controlled-release formulation because of low dissolution rate and poor bioavailability. Solid dispersion (SD) of GLZ consisted of hydroxypropyl cellulose (HPC-SSL) as a polymeric solubilizer was manufactured by hot melt extrusion (HME) technology. Then, controlled porosity osmotic pump (CPOP) tablet of gliclazide was designed to deliver drug in a controlled manner up to 16 h. The developed formulation was optimized for type and level of pore former and coating weight gain. The optimized formulation was found to exhibit zero order kinetics independent of pH and agitation speed but depends on osmotic pressure of dissolution media indicated that mechanism of drug release was osmotic pressure. The in vivo performance prediction of developed formulation using convolution approach revealed that the developed formulation was superior to the existing marketed extended-release formulation in terms of attaining steady state plasma levels and indicated adequate exposure in translating hypoglycemic response. The prototype solubilization method combined with controlled porosity osmotic pump based technique could provide a unique way to increase dissolution rate and bioavailability of many poorly water-soluble, narrow therapeutic index drugs used in diabetes, cardiovascular diseases, etc.

  4. IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS.

    Science.gov (United States)

    Meka, Venkata Srikanth; Yee, Phung; Sheshala, Ravi

    2016-01-01

    In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose

  5. Supramolecular Cocrystals of Gliclazide: Synthesis, Characterization and Evaluation.

    Science.gov (United States)

    Chadha, Renu; Rani, Dimpy; Goyal, Parnika

    2017-03-01

    To prepare the supramolecular cocrystals of gliclazide (GL, a BCS class II drug molecule) via mechanochemical route, with the goal of improving physicochemical and biopharmaceutical properties. Two cocrystals of GL with GRAS status coformers, sebacic acid (GL-SB; 1:1) and α-hydroxyacetic acid (GL-HA; 1:1) were screened out using liquid assisted grinding. The prepared cocrystals were characterized using thermal and analytical techniques followed by evaluation of antidiabetic activity and pharmacokinetic parameters. The generation of new, single and pure crystal forms was characterized by DSC and PXRD. The crystal structure determination from PXRD revealed the existence of both cocrystals in triclinic (P-1) crystal system. The hydrogen bonded network, determined by material studio was well supported by shifts in FTIR and SSNMR. Both the new solid forms displayed improved solubility, IDR, antidiabetic activity and pharmacokinetic parameters as compared to GL. The improvement in these physicochemical and biopharmaceutical properties corroborated the fact that the supramolecular cocrystallization may be useful in the development of pharmaceutical crystalline materials with interesting network and properties.

  6. Drug–drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats

    Science.gov (United States)

    Sultanpur, CM; Satyanarayana, S; Reddy, NS; Kumar, KE; Kumar, S

    2010-01-01

    Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drug–drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD –POD. Gliclazide (½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution. PMID:21264118

  7. Gradient HPLC method development and validation for Simultaneous estimation of Rosiglitazone and Gliclazide.

    Directory of Open Access Journals (Sweden)

    Uttam Singh Baghel

    2012-10-01

    Full Text Available Objective: The aim of present work was to develop a gradient RP-HPLC method for simultaneous analysis of rosiglitazone and gliclazide, in a tablet dosage form. Method: Chromatographic system was optimized using a hypersil C18 (250mm x 4.6mm, 5毺 m column with potassium dihydrogen phosphate (pH-7.0 and acetonitrile in the ratio of 60:40, as mobile phase, at a flow rate of 1.0 ml/min. Detection was carried out at 225 nm by a SPD-20A prominence UV/Vis detector. Result: Rosiglitazone and gliclazide were eluted with retention times of 17.36 and 7.06 min, respectively. Beer’s Lambert ’s Law was obeyed over the concentration ranges of 5 to 70 毺 g/ml and 2 to 12 毺 g/ml for rosiglitazone and gliclazide, respectively. Conclusion: The high recovery and low coefficients of variation confirm the suitability of the method for simultaneous analysis of both drugs in a tablets dosage form. Statistical analysis proves that the method is sensitive and significant for the analysis of rosiglitazone and gliclazide in pure and in pharmaceutical dosage form without any interference from the excipients. The method was validated in accordance with ICH guidelines. Validation revealed the method is specific, rapid, accurate, precise, reliable, and reproducible.

  8. Gliclazide mainly affects insulin secretion in second phase of type 2 diabetes mellitus

    NARCIS (Netherlands)

    Ligtenberg, JJM; van Haeften, TW

    We studied the effect of the acute administration of gliclazide at 160 mg on insulin release during hyperglycaemic clamps in 12 type 2 diabetes patients, age 50 +/- 9.0 years, diabetes duration 55 +/- 4.8 years, fasting blood glucose 9.6 +/- 2.1 mmol/L (means +/- SD). After a 210 min of

  9. A new cocrystal of Gliclazide with Tromethamine: Preparation and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Sousa, Marcus Lima; Silva, Francisca Celia da; Silva Filho, Silverio Ferreira da; Pereira, Andreia Cardoso; Santos, Adenilson Oliveira dos; Ribeiro, Paulo Roberto da Silva, E-mail: mrcs49@hotmail.com [Universidade Federal do Maranhao (UFMA), Sao Luis (Brazil)

    2016-07-01

    Full text: Gliclazide (GLZ) is an antidiabetic widely used for patients with Diabetes Mellitus Type II. This compound has low aqueous solubility (55 mg l{sup -1}) and low dissolution rate. Such characteristics are limiting factors that contribute to reducing its bioavailability. Studies show the cocrystals are a promising strategy to improve the physicochemical properties of drugs, such as dissolution rate and bioavailability[1]. The objective of present investigation was the preparation (by assisted liquid grinding) and characterization of a new cocrystal of GLZ with the coformer tromethamine (TRIS). The sample was synthesized in molar ratio 1:1 and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Thermogravimetry and Differential Thermal Analysis (TG/DTA). The DSC showed melting point different from the pure compounds, two endothermic events occurring: the first peak at 133.77 °C and the second peak at 146.97 °C, which may indicate the formation of the cocrystal. The thermal stability profile revealed three mass loss events for the TG. The first event indicated a peak weight loss at 161.8 °C, to 14.06% of the original mass. The second event showed peak temperature of 222.80 °C corresponding to 55.80% of mass. The third occurred at 305.0 °C with loss of 27.3% by mass. In the analysis DTA was observed an endothermic event with peak at 129.37 °C which may be due to phase transition characteristic of the coformador; another endothermic peak emerged at a temperature of 141.0 °C, which may be related to melting of the test compound. The results PXRD revealed changes in diffractograms of sample, showing crystallographic new peaks which did not occur in the spectra of pure compounds (GLZ and TRIS), indicating novel crystalline structure, and thus confirm the formation of the cocrystal. References: [1] Nanjwade, V. et al. J. Applied Pharmaceutical Sciences, v.1, n.1, p.1-5 (2011). (author)

  10. A new cocrystal of Gliclazide with Tromethamine: Preparation and characterization

    International Nuclear Information System (INIS)

    Sousa, Marcus Lima; Silva, Francisca Celia da; Silva Filho, Silverio Ferreira da; Pereira, Andreia Cardoso; Santos, Adenilson Oliveira dos; Ribeiro, Paulo Roberto da Silva

    2016-01-01

    Full text: Gliclazide (GLZ) is an antidiabetic widely used for patients with Diabetes Mellitus Type II. This compound has low aqueous solubility (55 mg l -1 ) and low dissolution rate. Such characteristics are limiting factors that contribute to reducing its bioavailability. Studies show the cocrystals are a promising strategy to improve the physicochemical properties of drugs, such as dissolution rate and bioavailability[1]. The objective of present investigation was the preparation (by assisted liquid grinding) and characterization of a new cocrystal of GLZ with the coformer tromethamine (TRIS). The sample was synthesized in molar ratio 1:1 and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Thermogravimetry and Differential Thermal Analysis (TG/DTA). The DSC showed melting point different from the pure compounds, two endothermic events occurring: the first peak at 133.77 °C and the second peak at 146.97 °C, which may indicate the formation of the cocrystal. The thermal stability profile revealed three mass loss events for the TG. The first event indicated a peak weight loss at 161.8 °C, to 14.06% of the original mass. The second event showed peak temperature of 222.80 °C corresponding to 55.80% of mass. The third occurred at 305.0 °C with loss of 27.3% by mass. In the analysis DTA was observed an endothermic event with peak at 129.37 °C which may be due to phase transition characteristic of the coformador; another endothermic peak emerged at a temperature of 141.0 °C, which may be related to melting of the test compound. The results PXRD revealed changes in diffractograms of sample, showing crystallographic new peaks which did not occur in the spectra of pure compounds (GLZ and TRIS), indicating novel crystalline structure, and thus confirm the formation of the cocrystal. References: [1] Nanjwade, V. et al. J. Applied Pharmaceutical Sciences, v.1, n.1, p.1-5 (2011). (author)

  11. Using resonance light scattering and UV/vis absorption spectroscopy to study the interaction between gliclazide and bovine serum albumin.

    Science.gov (United States)

    Zhang, Qiu-Ju; Liu, Bao-Sheng; Li, Gai-Xia; Han, Rong

    2016-08-01

    At different temperatures (298, 310 and 318 K), the interaction between gliclazide and bovine serum albumin (BSA) was investigated using fluorescence quenching spectroscopy, resonance light scattering spectroscopy and UV/vis absorption spectroscopy. The first method studied changes in the fluorescence of BSA on addition of gliclazide, and the latter two methods studied the spectral change in gliclazide while BSA was being added. The results indicated that the quenching mechanism between BSA and gliclazide was static. The binding constant (Ka ), number of binding sites (n), thermodynamic parameters, binding forces and Hill's coefficient were calculated at three temperatures. Values for the binding constant obtained using resonance light scattering and UV/vis absorption spectroscopy were much greater than those obtained from fluorescence quenching spectroscopy, indicating that methods monitoring gliclazide were more accurate and reasonable. In addition, the results suggest that other residues are involved in the reaction and the mode 'point to surface' existed in the interaction between BSA and gliclazide. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Limited sampling strategy models for estimating the AUC of gliclazide in Chinese healthy volunteers.

    Science.gov (United States)

    Huang, Ji-Han; Wang, Kun; Huang, Xiao-Hui; He, Ying-Chun; Li, Lu-Jin; Sheng, Yu-Cheng; Yang, Juan; Zheng, Qing-Shan

    2013-06-01

    The aim of this work is to reduce the cost of required sampling for the estimation of the area under the gliclazide plasma concentration versus time curve within 60 h (AUC0-60t ). The limited sampling strategy (LSS) models were established and validated by the multiple regression model within 4 or fewer gliclazide concentration values. Absolute prediction error (APE), root of mean square error (RMSE) and visual prediction check were used as criterion. The results of Jack-Knife validation showed that 10 (25.0 %) of the 40 LSS based on the regression analysis were not within an APE of 15 % using one concentration-time point. 90.2, 91.5 and 92.4 % of the 40 LSS models were capable of prediction using 2, 3 and 4 points, respectively. Limited sampling strategies were developed and validated for estimating AUC0-60t of gliclazide. This study indicates that the implementation of an 80 mg dosage regimen enabled accurate predictions of AUC0-60t by the LSS model. This study shows that 12, 6, 4, 2 h after administration are the key sampling times. The combination of (12, 2 h), (12, 8, 2 h) or (12, 8, 4, 2 h) can be chosen as sampling hours for predicting AUC0-60t in practical application according to requirement.

  13. Characterization of gliclazide-polyethylene glycol solid dispersion and its effect on dissolution

    Directory of Open Access Journals (Sweden)

    Moreshwar Pandharinath Patil

    2011-03-01

    Full Text Available The present study was initiated with the objective of studying the in vitro dissolution behavior of gliclazide from its solid dispersion with polyethylene glycol 6000. In this work, a solid dispersion of gliclazide with polyethylene glycol was prepared by the fusion method. In vitro dissolution study of gliclazide, its physical mixture and solid dispersion were carried out to demonstrate the effect of PEG 6000. Analytical techniques of FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry were used to characterize the drug in the physical mixtures and solid dispersions. The dissolution studies of solid dispersion and physical mixture showed greater improvement compared to that of the pure drug. The mechanisms for increased dissolution rate may include reduction of crystallite size, a solubilization effect of the carrier, absence of aggregation of drug crystallites, improved wettability and dispersbility of the drug from the dispersion, dissolution of the drug in the hydrophilic carrier or conversion of drug to an amorphous state. The FT-IR spectra suggested that there was no interaction between gliclazide and PEG 6000 when prepared as a solid dispersion. DSC and XRD study indicated that the drug was converted in the amorphous form.O presente trabalho foi realizado com o objetivo de estudar o comportamento in vitro da dissolução da gliclazida a partir da sua dispersão sólida com polietileno glicol 6000. Neste trabalho, as dispersões sólidas de gliclazida com polietileno glicol foram preparadas pelo método de fusão. Os estudo de dissolução in vitro da gliclazida, na mistura física e nas dispersões sólidas foram realizados para demonstrar o efeito de PEG 6000. Técnicas analíticas como espectroscopia FT-IR, calorimetria diferencial de varredura e difração de raios-X foram empregadas para caracterizar o fármaco nas misturas físicas e nas dispersoes sólidas. Os estudos de dissolução demonstraram maior

  14. The effect of glycation on bovine serum albumin conformation and ligand binding properties with regard to gliclazide

    Science.gov (United States)

    Żurawska-Płaksej, Ewa; Rorbach-Dolata, Anna; Wiglusz, Katarzyna; Piwowar, Agnieszka

    2018-01-01

    Albumin, the major serum protein, plays a variety of functions, including binding and transporting endogenous and exogenous ligands. Its molecular structure is sensitive to different environmental modifiers, among which glucose is one of the most significant. In vivo albumin glycation occurs under physiological conditions, but it is increased in diabetes. Since bovine serum albumin (BSA) may serve as a model protein in in vitro experiments, we aimed to investigate the impact of glucose-mediated BSA glycation on the binding capacity towards gliclazide, as well as the ability of this drug to prevent glycation of the BSA molecule. To reflect normo- and hyperglycemia, the conditions of the glycation process were established. Structural changes of albumin after interaction with gliclazide (0-14 μM) were determined using fluorescence quenching and circular dichroism spectroscopy. Moreover, thermodynamic parameters as well as energy transfer parameters were determined. Calculated Stern-Volmer quenching constants, as well as binding constants for the BSA-gliclazide complex, were lower for the glycated form of albumin than for the unmodified protein. The largest, over 2-fold, decrease in values of binding parameters was observed for the sample with 30 mM of glucose, reflecting the poorly controlled diabetic state, which indicates that the degree of glycation had a critical influence on binding with gliclazide. In contrast to significant changes in the tertiary structure of BSA upon binding with gliclazide, only slight changes in the secondary structure were observed, which was reflected by about a 3% decrease of the α-helix content of glycated BSA (regardless of glucose concentration) in comparison to unmodified BSA. The presence of gliclazide during glycation did not affect its progress. The results of this study indicate that glycation significantly changed the binding ability of BSA towards gliclazide and the scale of these changes depended on glucose concentration. It

  15. Effect of combined gliclazide/metformin treatment on oxidative stress, lipid profile, and hepatorenal functions in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Mansour Alsharidah

    2018-01-01

    Full Text Available Background: Type 2 diabetes is a chronic condition that requires pharmacotherapy interventions. Metformin and gliclazide are widely used drugs in monotherapy. However, their complementary action made utilization of the combination of these drugs an appealing approach. Aims: The study compared major therapeutic potentials of combined metformin/gliclazide treatment over metformin monotherapy based on the following parameters: oxidative stress, lipid profile, and hepatorenal functions. Subjects and methods: This is a comparative study was conducted from March 2015 to March 2016. The study screened 80 type 2 diabetic patients, of which 40 patients underwent combined metformin + gliclazide therapy (500 mg BD + 80 mg OD, respectively. The other 40 were matched for age and duration of diabetes mellitus with the previous group and received metformin monotherapy (500 mg BD. The levels of fasting blood glucose (FBG, total glycated hemoglobin (HbA1c, lipid peroxidation, total antioxidant capacity, serum creatinine, aspartate and alanine transaminases, total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins were measured according to the standard methods. Results: Oxidative stress, lipid profile, and hepatorenal functions were comparable in patients of both groups. However, patients on metformin treatment showed significantly lower levels of FBG [7.61 (6.70–8.89 mmol/L vs. 9.00 (7.30–10.68 mmol/L; P = .022] and HBA1c [7.00 (6.40–7.65% vs. 8.20 (7.20–9.75%; P < .001] compared to those on combined therapy. Conclusion: Oxidative stress, lipids profile, and hepatorenal functions were not different in patients who were on combined metformin/gliclazide therapy and compared to those metformin alone. In contrast, glycemic control was poor in the diabetic patients undergoing combined therapy. Keywords: Diabetes mellitus, Gliclazide, Glucose, Lipids, Metformin, Oxidative stress

  16. Solubility of Gliclazide and Ion-Molecular Interactions with Aminopropanol in Aqueous Solutions

    Science.gov (United States)

    Hamdan, Imad I.; El-Sabawi, Dina; Abu-Dahab, Rana

    2018-01-01

    A new salt of gliclazide (GZD) was prepared and was shown to have a significantly higher aqueous solubility at physiological pH together with superior dissolution profiles in comparison to GZD employing an organic amino-alcohol base. Characterization by NMR, IR, DSC, conductometry and HPLC techniques concluded that an ion pair salt is formed between acidic GZD and basic aminopropanol (AMP). In addition to the presence of about 5% tightly bound water, hydrogen bonds appeared to form extensively between GZD, AMP and water molecules. Unlike many of solubility enhancing approaches, the salt did not hamper the permeability of GZD as shown by transport through Caco-2 cells model. In vivo studies on rats confirmed that the blood glucose lowering effect of GZD-AMP was significantly higher and more rapid compared to parent GZD indicating an enhanced overall performance of the prepared salt.

  17. Experimental and computational study on molecular structure and vibrational analysis of an antihyperglycemic biomolecule: Gliclazide

    Science.gov (United States)

    Karakaya, Mustafa; Kürekçi, Mehmet; Eskiyurt, Buse; Sert, Yusuf; Çırak, Çağrı

    2015-01-01

    In present study, the experimental and theoretical harmonic vibrational frequencies of gliclazide molecule have been investigated. The experimental FT-IR (400-4000 cm-1) and Laser-Raman spectra (100-4000 cm-1) of the molecule in the solid phase were recorded. Theoretical vibrational frequencies and geometric parameters (bond lengths and bond angles) have been calculated using ab initio Hartree Fock (HF), density functional theory (B3LYP hybrid function) methods with 6-311++G(d,p) and 6-31G(d,p) basis sets by Gaussian 09W program. The assignments of the vibrational frequencies were performed by potential energy distribution (PED) analysis by using VEDA 4 program. Theoretical optimized geometric parameters and vibrational frequencies have been compared with the corresponding experimental data, and they have been shown to be in a good agreement with each other. Also, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies have been found.

  18. In Vitro–In Vivo Correlation for Gliclazide Immediate-Release Tablets Based on Mechanistic Absorption Simulation

    OpenAIRE

    Grbic, Sandra; Parojcic, Jelena; Ibric, Svetlana; Djuric, Zorica

    2010-01-01

    The aim of this study was to develop a drug-specific absorption model for gliclazide (GLK) using mechanistic gastrointestinal simulation technology (GIST) implemented in GastroPlusTM software package. A range of experimentally determined, in silico predicted or literature data were used as input parameters. Experimentally determined pH-solubility profile was used for all simulations. The human jejunum effective permeability (Peff) value was estimated on the basis of in vitro measured Caco-2 p...

  19. Effect of combined gliclazide/metformin treatment on oxidative stress, lipid profile, and hepatorenal functions in type 2 diabetic patients.

    Science.gov (United States)

    Alsharidah, Mansour; Algeffari, Metab; Abdel-Moneim, Abdel-Moneim Hafez; Lutfi, Mohamed Faisal; Alshelowi, Haila

    2018-01-01

    Type 2 diabetes is a chronic condition that requires pharmacotherapy interventions. Metformin and gliclazide are widely used drugs in monotherapy. However, their complementary action made utilization of the combination of these drugs an appealing approach. The study compared major therapeutic potentials of combined metformin/gliclazide treatment over metformin monotherapy based on the following parameters: oxidative stress, lipid profile, and hepatorenal functions. This is a comparative study was conducted from March 2015 to March 2016. The study screened 80 type 2 diabetic patients, of which 40 patients underwent combined metformin + gliclazide therapy (500 mg BD + 80 mg OD, respectively). The other 40 were matched for age and duration of diabetes mellitus with the previous group and received metformin monotherapy (500 mg BD). The levels of fasting blood glucose (FBG), total glycated hemoglobin (HbA1c), lipid peroxidation, total antioxidant capacity, serum creatinine, aspartate and alanine transaminases, total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins were measured according to the standard methods. Oxidative stress, lipid profile, and hepatorenal functions were comparable in patients of both groups. However, patients on metformin treatment showed significantly lower levels of FBG [7.61 (6.70-8.89) mmol/L vs. 9.00 (7.30-10.68) mmol/L; P = .022] and HBA1c [7.00 (6.40-7.65)% vs. 8.20 (7.20-9.75)%; P metformin/gliclazide therapy and compared to those metformin alone. In contrast, glycemic control was poor in the diabetic patients undergoing combined therapy.

  20. A randomized controlled trial to compare the effects of sulphonylurea gliclazide MR (modified release) and the DPP-4 inhibitor vildagliptin on glycemic variability and control measured by continuous glucose monitoring (CGM) in Brazilian women with type 2 diabetes.

    Science.gov (United States)

    Vianna, Andre Gustavo Daher; Lacerda, Claudio Silva; Pechmann, Luciana Muniz; Polesel, Michelle Garcia; Marino, Emerson Cestari; Faria-Neto, Jose Rocha

    2018-05-01

    This study aims to evaluate whether there is a difference between the effects of vildagliptin and gliclazide MR (modified release) on glycemic variability (GV) in women with type 2 diabetes (T2DM) as evaluated by continuous glucose monitoring (CGM). An open-label, randomized study was conducted in T2DM women on steady-dose metformin monotherapy which were treated with 50 mg vildagliptin twice daily or 60-120 mg of gliclazide MR once daily. CGM and GV indices calculation were performed at baseline and after 24 weeks. In total, 42 patients (age: 61.9 ± 5.9 years, baseline glycated hemoglobin (HbA1c): 7.3 ± 0.56) were selected and 37 completed the 24-week protocol. Vildagliptin and gliclazide MR reduced GV, as measured by the mean amplitude of glycemic excursions (MAGE, p = 0.007 and 0.034, respectively). The difference between the groups did not reach statistical significance. Vildagliptin also significantly decreased the standard deviation of the mean glucose (SD) and the mean of the daily differences (MODD) (p = 0.007 and 0.030). Vildagliptin and gliclazide MR similarly reduced the MAGE in women with T2DM after 24 weeks of treatment. Further studies are required to attest differences between vildagliptin and gliclazide MR regarding glycemic variability. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. A double-blind, randomized trial, including frequent patient–physician contacts and Ramadan-focused advice, assessing vildagliptin and gliclazide in patients with type 2 diabetes fasting during Ramadan: the STEADFAST study

    Directory of Open Access Journals (Sweden)

    Hassanein M

    2014-05-01

    Full Text Available Mohamed Hassanein,1 Khalifa Abdallah,2 Anja Schweizer31Betsi Cadwaladr University Health Board, Wales, United Kingdom; 2Clinical Research Center, Alexandria University Hospital, Alexandria, Egypt; 3Global Medical Affairs, Novartis Pharma AG, Basel, SwitzerlandBackground: Several observational studies were conducted with vildagliptin in patients with type 2 diabetes mellitus (T2DM fasting during Ramadan, showing significantly lower incidences of hypoglycemia with vildagliptin versus sulfonylureas, including gliclazide. It was of interest to complement the existing real-life evidence with data from a randomized, double-blind, clinical trial.Clinical Trials Identifier: NCT01758380.Methods: This multiregional, double-blind study randomized 557 patients with T2DM (mean glycated hemoglobin [HbA1c], 6.9%, previously treated with metformin and any sulfonylurea to receive either vildagliptin (50 mg twice daily or gliclazide plus metformin. The study included four office visits (three pre-Ramadan and multiple telephone contacts, as well as Ramadan-focused advice. Hypoglycemic events were assessed during Ramadan; HbA1c and weight were analyzed before and after Ramadan.Results: The proportion of patients reporting confirmed (<3.9 mmol/L and/or severe hypoglycemic events during Ramadan was 3.0% with vildagliptin and 7.0% with gliclazide (P=0.039; one-sided test, and this was 6.0% and 8.7%, respectively, for any hypoglycemic events (P=0.173. The adjusted mean change pre- to post-Ramadan in HbA1c was 0.05%±0.04% with vildagliptin and -0.03%±0.04% with gliclazide, from baselines of 6.84% and 6.79%, respectively (P=0.165. In both groups, the adjusted mean decrease in weight was -1.1±0.2 kg (P=0.987. Overall safety was similar between the treatments.Conclusion: In line with the results from previous observational studies, vildagliptin was shown in this interventional study to be an effective, safe, and well-tolerated treatment in patients with T2DM fasting

  2. Development of Analytical Method for Detection of Some ...

    African Journals Online (AJOL)

    All compounds (hydrochlorothiazide, gliclazide, diclofenac-Na and mefenamic acid) were analysed in negative ion (NI) mode and eluted off the column with a mobile phase consisting of (A) 0.1% formic acid (FA) in deionised water (DIW) and (B) 40% acetonitrile (ACN) in methanol (MeOH) at 0.3 ml/min. Mass spectrometry ...

  3. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

    NARCIS (Netherlands)

    Patel, A.; MacMahon, S; Chalmers, J.; Neal, B.; Billot, L.; Woodward, M.; Marre, M.; Cooper, M.; Glasziou, P.; Grobbee, D.E.; Hamet, P.; Harrap, S.; Heller, S.; Liu, L.; Mancia, G.; Mogensen, C.E.; Pan, C.; Poulter, N.; Rodgers, A.; Williams, B.; Bompoint, S.; Galan, B.E. de; Joshi, R.; Travert, F.

    2008-01-01

    BACKGROUND: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. METHODS: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide

  4. Vildagliptin has the same safety profile as a sulfonylurea on bone metabolism and bone mineral density in post-menopausal women with type 2 diabetes: a randomized controlled trial.

    Science.gov (United States)

    Vianna, Andre Gustavo Daher; de Lacerda, Claudio Silva; Pechmann, Luciana Muniz; Polesel, Michelle Garcia; Marino, Emerson Cestari; Borba, Victoria Zeghbi Cochenski; Barreto, Fellype de Carvalho

    2017-01-01

    Several antidiabetic therapies affect bone metabolism. Sulfonylureas have the lowest impact on bone among oral antidiabetics. The objective of this study is to compare the effects of vildagliptin and gliclazide modified release (MR) on bone turnover markers (BTMs) and bone mineral density (BMD) in postmenopausal women with uncontrolled type 2 diabetes (T2D). Forty-two postmenopausal women with uncontrolled T2D were randomly allocated into vildagliptin or gliclazide MR (control) groups. The primary endpoint was the change in the BTMs in months 6 and 12 compared with the baseline. The secondary endpoint was the variation in the BMD, which was assessed via dual-energy X-ray absorptiometry at the lumbar spine, femoral neck and total hip at baseline and month 12. After a 12-month treatment, the BTM serum carboxy-terminal telopeptide of type 1 collagen increased 0.001 ± 0.153 ng/mL in the vildagliptin group versus 0.008 ± 0.060 ng/mL in the gliclazide MR group ( p  = 0.858). The serum osteocalcin, serum amino-terminal propeptide of procollagen type I and urinary amino-terminal telopeptide of type 1 collagen remained stable in both groups, and there was no statistically significant difference between the effect of vildagliptin and gliclazide MR on these variables. The lumbar spine BMD did not change in the vildagliptin or gliclazide MR groups after a 12-month treatment (0.000 ± 0.025 g/cm 2 versus -0.008 ± 0.036, respectively, p  = 0.434). Furthermore, there was a similar lack of change in the femoral neck and total hip BMD values in both treatments. Bone turnover markers and BMD remained unchanged after a 12-month treatment in both groups, which suggests that vildagliptin has the same safety profile as gliclazide MR on bone metabolism. Trial Registration ClinicalTrials.gov number NCT01679899.

  5. In vivo and in vitro attenuation of naloxone-precipitated experimental opioid withdrawal syndrome by insulin and selective KATP channel modulator.

    Science.gov (United States)

    Singh, Prabhat; Sharma, Bhupesh; Gupta, Surbhi; Sharma, B M

    2015-01-01

    Opiate exposure for longer duration develops state of dependence in humans and animals, which is revealed by signs and symptoms of withdrawal precipitated by opioid receptor antagonists. The sudden withdrawal of opioids produces a withdrawal syndrome in opioid-dependent subjects. Insulin and ATP-sensitive potassium (KATP) channel-mediated glucose homeostasis have been shown to modulate morphine withdrawal. Present study has been structured to investigate the role of insulin and pharmacological modulator of KATP channel (gliclazide) in experimental morphine withdrawal syndrome, both invivo and invitro. In this study, naloxone-precipitated morphine withdrawal syndrome in mice (invivo) as well as in rat ileum (invitro) were utilized to assess opioid withdrawal phenomenon. Morphine withdrawal syndromes like jumping and rearing frequency, forepaw licking, circling, fore paw tremor, wet dog shake, sneezing, overall morphine withdrawal severity (OMWS), serum glucose, brain malondialdehyde (MDA), glutathione (GSH), nitrite/nitrate, and calcium (Ca(+2)) were assessed. Naloxone has significantly increased morphine withdrawal syndrome, both invivo and invitro. Insulin and gliclazide have significantly attenuated, naloxone induced behavioral changes like jumping and rearing frequency, forepaw licking, wet dog shake, sneezing, straightening, circling, OMWS, and various biochemical impairments such as serum glucose, brain MDA, GSH, nitrite/nitrate, and Ca(+2) in morphine-dependent animals (invivo). In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation. Insulin and gliclazide (KATP channel blocker) have attenuated naloxone-precipitated morphine withdrawal syndrome, both invivo and invitro. Thus, insulin and KATP channel modulation may provide new avenues for research in morphine withdrawal.

  6. Oral Hypoglycaemic Drugs in Alloxan-Induced Diabetes Mellitus in Dogs

    Directory of Open Access Journals (Sweden)

    É. Balogh

    2008-01-01

    Full Text Available The effect of the alpha-glycosidase inhibitor acarbose, the insulin sensitiser metformin and the insulin secretiser gliclazide on blood glucose level of dogs were examined in experimental diabetes. Dogs were randomly divided into three groups. During the first week of the experimental period control blood glucose data were determined. During the subsequent five weeks, the first group (n = 6 was administered acarbose (200 mg/dog/day, the second (n = 5 was treated with metformin (1700 mg/dog/day, and the third was given gliclazide (160 mg/dog/day. The drug was administered twice daily when feeding at 7:00 and 15:00 h. The average difference between postprandial and fasting blood glucose was determined for the treated and the control period, and the statistical significance of their difference (mean decrease was evaluated by two-sampled t-test. The mean decrease in blood glucose was 0.49 mmol/l (P = 0.09 for acarbose, 1.15 mmol/l (P = 0.01 for metformin, and 0.08 mmol/l (P = 0.88 for gliclazide. According to the results of statistical evaluation, metformin was the only drug that caused a significant decrease in postprandial blood glucose.

  7. Effect of alogliptin on hypertensive chronic kidney disease patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Amira Said

    2018-02-01

    Full Text Available Background Diabetes mellitus (DM is a leading cause of chronic kidney disease (CKD. The antihyperglycemic treatment options for patients with Type 2 DM are limited because of safety and tolerability concerns. Aims To retrospectively assess the effect of using Alogliptin; a dipeptidyl peptidase-4 inhibitor (DPP-4i along with conventional gliclazide: a sulphonylurea (SU on renal outcomes and glycaemic control in T2DM patients with mild CKD and hypertension. Methods A total of 76 patient records (38 males and 38 females of patient ages 40–60 were analysed from the kidney unit at Punjab Care hospital, Lahore, Pakistan. All patients had a confirmed history of T2DM with mild CKD and established hypertension. Eligible patients were divided into two groups of 38 individuals each. Group SU received gliclazide monotherapy (SU or Alogliptin (DPP-4i+gliclazide (SU add on therapy. All patients were followed up for 12 months. Results The alogliptin (DPP-4i plus gliclazide (SU add on therapy group, in comparison to the group only receiving gliclazide (SU, showed a significant difference in eGFR values. The mean±SD GFR values post 12 months were 74.8±0.31 (95%CI:74.8±0.09;74.7–74.9 and 76.1±0.25 (95%CI: 76.1±0.08;76.0-76.2 for SU vs. SU+DPP-4i, respectively, with mean calculated effect size of 1.6,. HbA1c, 1,5 AG and ipid profile values have significantly changed (p<0.05 while blood pressure values showed no change. The mean±SD systolic blood pressure readings post 12 months for for SU vs. SU+DPP-4i were 131.4±10.4 (95% CI 131.4±3.3;128.1– 134.7, and 131.8±9.9 (95%CI 131.8±3; 128.8–134.8, respectively. Conclusion In the present study, patients using alogliptin in addition to sulfonyl urea showed improved glycaemic control and lipid profile without increased occurrence of hypoglycaemia. We concluded that, DPP-4i inhibitors are safe treatment options for patients with type 2 diabetes and mild degree of renal impairment.

  8. Preparation and characterization of cross-linked excipient of coprocessed xanthan gum-acacia gum as matrix for sustained release tablets

    Science.gov (United States)

    Surini, Silvia; Wati, Dina Risma; Syahdi, Rezi Riadhi

    2018-02-01

    Sustained release tablet is solid dosage form which is designed to release drugs slowly in the body. This research was intended to prepare and characterize the cross-linked excipients of co-processed xanthan gum-acacia gum (CL-Co-XGGA) as matrices for sustained release tablets with gliclazide as a model drug. CL-Co-XGGA excipients were cross-linked materials of co-processed excipients of xanthan gum-acacia gum (Co-XGGA) using sodium trimetaphosphate. Co-processed excipients of xanthan gum-acacia gum were prepared in the ratio of each excipient 1:2, 1:1 and 2:1. Co-XGGA and CL-Co-XGGA excipients were characterized physically, chemically and functionally. Then, the sustained release (SR) tablets were formulated by wet granulation method using CL-Co-XGGA excipients as matrices. Also, the dissolution study of the gliclazide SR tablets was carried out in phosphate buffer medium pH 7,4 containing sodium lauryl sulphate 0.2% for 12 hours. The results showed that the degree of substitution (DS) of CL-Co-XGGA 1:2, 1:1, 2:1 excipients were respectively 0.067, 0.082 and 0.08. Besides that, the excipients gel strengths were 14.03, 17.27 and 20,70 gF, respectively. The cross-linked excipients had improved flow properties and swelling capability compared to the Co-XGGA excipients. The results of the gliclazide SR tablets evaluations showed that all tablets were passed all tablet requirements. Moreover, the gliclazide release from SR tablets F1 - F6 revealed the sustained release profile, which was following zero order kinetics (F1, F2, F3, F6) and Higuchi kinetics (F4 and F5). It could be concluded that the obtained CL-Co-XGGA excipients might be used as matrices for sustained release tablets and could retard drug release up to 8 until 32 hours.

  9. Co-extrusion as a processing technique to manufacture a dual sustained release fixed-dose combination product.

    Science.gov (United States)

    Vynckier, An-Katrien; Voorspoels, Jody; Remon, Jean Paul; Vervaet, Chris

    2016-05-01

    This study aimed to design a fixed-dose combination dosage form which provides a sustained release profile for both the freely water-soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus. Hot-melt co-extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed-dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug. It was clear that co-extrusion was perfectly suited to produce a fixed-dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA(®) 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl-loaded CAPA(®) 6506 core of the co-extrudate. To obtain a complete gliclazide release over 24-h solubilization in Kollidon(®) VA, added as a second polymer to the CAPA(®) 6506 in the coat, was needed. Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co-extrusion. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

  10. Hypoglycaemia when adding sulphonylurea to metformin

    DEFF Research Database (Denmark)

    Andersen, Stig Ejdrup; Christensen, Mikkel

    2016-01-01

    AIMS: The risk of hypoglycaemia may differ among sulphonylureas (SUs), but evidence from head-to-head comparisons is sparse. Performing a network meta-analysis to use indirect evidence from randomized controlled trials (RCTs), we compared the relative risk of hypoglycaemia with newer generation SUs...... when added to metformin. METHODS: A systematic review identified RCTs lasting 12-52 weeks and evaluating SUs added to inadequate metformin monotherapy (≥1000 mg/day) in type 2 diabetes. Adding RCTs investigating the active comparators from the identified SU trials, we established a coherent network...... of hypoglycaemia was lowest with gliclazide compared to glipizide (OR 0.22, CrI: 0.05 to 0.96), glimepiride (OR 0.40, CrI: 0.13 to 1.27), and glibenclamide (OR 0.21, CrI: 0.03 to 1.48). A major limitation is varying definitions of hypoglycaemia across studies. CONCLUSIONS: When added to metformin, gliclazide...

  11. Hypoglycemic of Cajanus scarabaeoides in glucose overloaded and streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Suman Pattanayak, Siva Shankar Nayak, Durgaprasad Panda and Vikas Shende

    2009-12-01

    Full Text Available In light of traditional claim of Cajanus scarabaeoides (L in the treatment of diabetes, we studied the effects of different solvent extracts in normal, glucose over loaded normal rats and streptozotocin-induced diabetic rats. The methanolic extract (500 mg/kg orally was produce significantly reduce blood glucose level at normal, glucose over loaded normal rats, and streptozotocin-induced diabetic rats after 15 days treatment; whereas petroleum ether and chloroform extract (500 mg/kg orally did not exhibit any significant effect on three groups of rats. Histopathology studies on pancreas of streptozotocin-induced diabetic rats shows inflammatory changes in pancreatic islets, results from selective destroy of insulin producing β-cells. These changes are inhibited by C. scarabaeoides methanolic extract and gliclazide. The antidiabetic activity of methanolic extract may be due to the presence of flavonoids.

  12. Simultaneous Quantification of Antidiabetic Agents in Human Plasma by a UPLC-QToF-MS Method.

    Directory of Open Access Journals (Sweden)

    Mariana Millan Fachi

    Full Text Available An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method for the simultaneous quantification of chlorpropamide, glibenclamide, gliclazide, glimepiride, metformin, nateglinide, pioglitazone, rosiglitazone, and vildagliptin in human plasma was developed and validated, using isoniazid and sulfaquinoxaline as internal standards. Following plasma protein precipitation using acetonitrile with 1% formic acid, chromatographic separation was performed on a cyano column using gradient elution with water and acetonitrile, both containing 0.1% formic acid. Detection was performed in a quadrupole time-of-flight analyzer, using electrospray ionization operated in the positive mode. Data from validation studies demonstrated that the new method is highly sensitive, selective, precise (RSD 0.99, free of matrix and has no residual effects. The developed method was successfully applied to volunteers' plasma samples. Hence, this method was demonstrated to be appropriate for clinical monitoring of antidiabetic agents.

  13. A cost-effectiveness analysis of intensive therapy of type 2 diabetes mellitus (results of Steno-2 study

    Directory of Open Access Journals (Sweden)

    Yury Shavkatovich Khalimov

    2011-06-01

    Full Text Available Intensive combined therapy including modification of the lifestyle, intake of metformin and/or sulfonylureas, insulin treatment in the absence ofadequate HbAc1 control, hypolipidemic, early antihypertensive and antithrombotic therapy not only decreases the frequency of DM2 complicationsbut also reduces the total cost of the treatment (1.8 times compared with traditional therapy. Reduction in cardiovascular mortality achieved inSTENO-2 was due to intense control of risk factors at early stages of therapy with the use of modified release gliclazide (Diabeton MV. This treatmentis considered to be not only more efficacious than routine therapy but also to significantly reduce the cost of the management of DM2

  14. Non-invasive phenotyping and drug testing in single cardiomyocytes or beta-cells by calcium imaging and optogenetics.

    Directory of Open Access Journals (Sweden)

    Yu-Fen Chang

    Full Text Available Identification of drug induced electrical instability of the heart curtails development, and introduction, of potentially proarrhythmic drugs. This problem usually requires complimentary contact based approaches such as patch-clamp electrophysiology combined with field stimulation electrodes to observe and control the cell. This produces data with high signal to noise but requires direct physical contact generally preventing high-throughput, or prolonged, phenotyping of single cells or tissues. Combining genetically encoded optogenetic control and spectrally compatible calcium indicator tools into a single adenoviral vector allows the analogous capability for cell control with simultaneous cellular phenotyping without the need for contact. This combination can be applied to single rodent primary adult cardiomyocytes, and human stem cell derived cardiomyocytes, enabling contactless small molecule evaluation for inhibitors of sodium, potassium and calcium channels suggesting it may be useful for early toxicity work. In pancreatic beta-cells it reveals the effects of glucose and the KATP inhibitor gliclazide.

  15. Sulfonylurea therapy improves glucose disposal without changing skeletal muscle GLUT4 levels in noninsulin-dependent diabetes mellitus subjects

    DEFF Research Database (Denmark)

    Vestergaard, H; Weinreb, J E; Rosen, A S

    1995-01-01

    alteration in GLUT4 levels expressed either per microgram membrane protein or per DNA. In summary, the improvement in glycemic control and glucose disposal in NIDDM subjects receiving gliclazide therapy cannot be explained by increased expression of GLUT4 in muscle. Thus, therapeutic effects on insulin......A major pathological feature of noninsulin-dependent diabetes (NIDDM) is defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies widely and is not different from that in controls. Thus......, longitudinal studies are needed to assess whether changes in GLUT4 expression in muscle of NIDDM subjects could be responsible for changes in glucose disposal. The question is timely because recent studies in transgenic mice show that increasing GLUT4 expression can increase insulin-stimulated glucose uptake...

  16. Consensus recommendations on sulfonylurea and sulfonylurea combinations in the management of Type 2 diabetes mellitus – International Task Force

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2018-01-01

    Full Text Available For decades, sulfonylureas (SUs have been important drugs in the antidiabetic therapeutic armamentarium. They have been used as monotherapy as well as combination therapy. Focus on newer drugs and concerns about the risk of severe hypoglycemia and weight gain with some SUs have led to discussion on their safety and utility. It has to be borne in mind that the adverse events associated with SUs should not be ascribed to the whole class, as many modern SUs, such as glimepiride and gliclazide modified release, are associated with better safety profiles. Furthermore, individualization of treatment, using SUs in combination with other drugs, backed with careful monitoring and patient education, ensures maximum benefits with minimal side effects. The current guidelines, developed by experts from Africa, Asia, and the Middle East, promote the safe and smart use of SUs in combination with other glucose-lowering drugs.

  17. Application of a Fast Separation Method for Anti-diabetics in Pharmaceuticals Using Monolithic Column: Comparative Study With Silica Based C-18 Particle Packed Column.

    Science.gov (United States)

    Hemdan, A; Abdel-Aziz, Omar

    2018-04-01

    Run time is a predominant factor in HPLC for quality control laboratories especially if there is large number of samples have to be analyzed. Working at high flow rates cannot be attained with silica based particle packed column due to elevated backpressure issues. The use of monolithic column as an alternative to traditional C-18 column was tested for fast separation of pharmaceuticals, where the results were very competitive. The performance comparison of both columns was tested for separation of anti-diabetic combination containing Metformin, Pioglitazone and Glimepiride using Gliclazide as an internal standard. Working at high flow rates with less significant backpressure was obtained with the monolithic column where the run time was reduced from 6 min in traditional column to only 1 min in monolithic column with accepted resolution. The structure of the monolith contains many pores which can adapt the high flow rate of the mobile phase. Moreover, peak symmetry and equilibration time were more efficient with monolithic column.

  18. The effect of control of diabetes mellitus on plasma T4, T3, rT3 levels and half muscle relaxation period

    International Nuclear Information System (INIS)

    Ismail, A.A.; Hafiez, A.A.; Sayed, S.N.; Abbas, E.Z.; Halawa, F.A.; Youssef, M.M.

    1984-01-01

    25 diabetics of the maturity onset type who showed no clinical evidence of either peripheral neruropathy or diabetic amyotrophy were selected for this study. All patients were subjected to the following investigations: estimation of half muscle relaxation period of the quadriceps muscle knee-jerk, measurement of plasma levels of thyroxine (T 4 ), triiodothyronine (T 3 ) and reverse triiodothronine (rT 3 ), determination of fasting and two hours postprandial blood sugar levels. The quadriceps muscle relaxation period in uncontrolled diabetics was significantly longer than in normals. Control of diabetes by glibenclamide or gliclazide did not cause a significant change in muscle relaxation period. There was also no significant difference between the effects of the two drugs. (author)

  19. Effects of drugs on platelet function.

    Science.gov (United States)

    Morse, E E

    1977-01-01

    Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.

  20. Unchanged gene expression of glycogen synthase in muscle from patients with NIDDM following sulphonylurea-induced improvement of glycaemic control

    DEFF Research Database (Denmark)

    Vestergaard, H; Lund, S; Bjørbaek, C

    1995-01-01

    We have previously shown that the mRNA expression of muscle glycogen synthase is decreased in non-insulin-dependent diabetic (NIDDM) patients; the objective of the present protocol was to examine whether the gene expression of muscle glycogen synthase in NIDDM is affected by chronic sulphonylurea...... as enhanced beta-cell responses to an oral glucose load. During euglycaemic, hyperinsulinaemic clamp (2 mU x kg-1 x min-1) in combination with indirect calorimetry, a 35% (p=0.005) increase in whole-body insulin-stimulated glucose disposal rate, predominantly due to an increased non-oxidative glucose....... In conclusion, improved blood glucose control in gliclazide-treated obese NIDDM patients has no impact on the gene expression of muscle glycogen synthase....

  1. Bullous pemphigoid induced by vildagliptin: a report of three cases.

    Science.gov (United States)

    Béné, Johana; Jacobsoone, Aurélie; Coupe, Patrick; Auffret, Marine; Babai, Samy; Hillaire-Buys, Dominique; Jean-Pastor, Marie-Josèphe; Vonarx, Marlène; Vermersch, Annie; Tronquoy, Anne-Fleur; Gautier, Sophie

    2015-02-01

    To report three cases of bullous pemphigoid in patients treated with vildagliptin. Case 1: An 86-year-old woman presented with bullous pemphigoid after 1 month of treatment with vildagliptin and metformin. After introduction of clobetasol, the symptoms resolved although vildagliptin was continued. However, the skin lesions reappeared 3 months later. Sustained remission was achieved only after definitive withdrawal of vildagliptin. Case 2: A 79-year-old man presented with bullous pemphigoid after 37-month treatment with gliclazide, vildagliptin and metformin. The disease at first responded to clobetasol but 3 months later the lesions reappeared. They finally regressed when the gliptin was discontinued. Case 3: A 77-year-old woman, treated with gliclazide and vildagliptin for 26 months, presented with bullous pemphigoid, which responded well to discontinuation of the gliptin and topical clobetasol. Gliptins are new molecules for treatment of type 2 diabetes mellitus, which have been suspected of implication in bullous pemphigoid. Such cases have been described in the literature (seven with vildagliptin and three with sitagliptin). In nine of these cases, the gliptin was associated with metformin, but the latter had never been considered responsible. The mechanism implicated in the development of bullous pemphigoid has not yet been clearly identified, but may involve a modified immune response or alteration of the antigenic properties of the epidermal basement membrane. These reports support the risk of bullous pemphigoid in patients exposed to gliptins. © 2014 Société Française de Pharmacologie et de Thérapeutique.

  2. Comparative evaluation of the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods.

    Science.gov (United States)

    Devgan, Manish; Nanda, Arun; Ansari, Shahid Husain

    2013-09-01

    The aim of the present study was to assess the anti-diabetic activity of Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by optimized conventional and non conventional extraction methods. Aqueous and ethanol extracts of Pterocarpus marsupium heartwood were prepared by conventional methods (infusion, decoction, maceration and percolation) and non conventional methods, such as ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE). The crude aqueous extracts were administered orally to both normal and alloxan induced male albino rats (Sprague-Dawley strain). The experimental set up consisted of 48 male albino rats divided into 6 groups: Normal control, diabetic control (sterile normal saline, 1 ml/100 g body weight), standard (gliclazide, 25 mg/1000g of body weight), groups 4-6 (crude aqueous percolation, optimized UAE and MAE extract, 250 mg/1000g of body weight). In acute treatment, the reduction of blood glucose level was statistically significant with the oral administration of UAE and percolation aqueous extracts to the hyperglycemic rats. In sub-acute treatment, the UAE aqueous extract led to consistent and statistically significant (p<0.001) reduction in the blood glucose levels. There was no abnormal change in body weight of the hyperglycemic animals after 10 days of administration of plant extracts and gliclazide. This study justifies the traditional claim and provides a rationale for the use of Pterocarpus marsupium to treat diabetes mellitus. The antidiabetic activity of Pterocarpus marsupium can be enhanced by extracting the heartwood by non conventional method of UAE.

  3. Analysis of drug-protein binding using on-line immunoextraction and high-performance affinity microcolumns: Studies with normal and glycated human serum albumin.

    Science.gov (United States)

    Matsuda, Ryan; Jobe, Donald; Beyersdorf, Jared; Hage, David S

    2015-10-16

    A method combining on-line immunoextraction microcolumns with high-performance affinity chromatography (HPAC) was developed and tested for use in examining drug-protein interactions with normal or modified proteins. Normal human serum albumin (HSA) and glycated HSA were used as model proteins for this work. High-performance immunoextraction microcolumns with sizes of 1.0-2.0 cm × 2.1mm i.d. and containing anti-HSA polyclonal antibodies were developed and tested for their ability to bind normal HSA or glycated HSA. These microcolumns were able to extract up to 82-93% for either type of protein at 0.05-0.10 mL/min and had a binding capacity of 0.34-0.42 nmol HSA for a 1.0 cm × 2.1mm i.d. microcolumn. The immunoextraction microcolumns and their adsorbed proteins were tested for use in various approaches for drug binding studies. Frontal analysis was used with the adsorbed HSA/glycated HSA to measure the overall affinities of these proteins for the drugs warfarin and gliclazide, giving comparable values to those obtained previously using similar protein preparations that had been covalently immobilized within HPAC columns. Zonal elution competition studies with gliclazide were next performed to examine the specific interactions of this drug at Sudlow sites I and II of the adsorbed proteins. These results were also comparable to those noted in prior work with covalently immobilized samples of normal HSA or glycated HSA. These experiments indicated that drug-protein binding studies can be carried out by using on-line immunoextraction microcolumns with HPAC. The same method could be used in the future with clinical samples and other drugs or proteins of interest in pharmaceutical studies or biomedical research. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Development and validation of analytical method for the estimation of nateglinide in rabbit plasma

    Directory of Open Access Journals (Sweden)

    Nihar Ranjan Pani

    2012-12-01

    Full Text Available Nateglinide has been widely used in the treatment of type-2 diabetics as an insulin secretogoga. A reliable, rapid, simple and sensitive reversed-phase high performance liquid chromatography (RP-HPLC method was developed and validated for determination of nateglinide in rabbit plasma. The method was developed on Hypersil BDSC-18 column (250 mm×4.6 mm, 5 mm using a mobile phase of 10 mM phosphate buffer (pH 2.5 and acetonitrile (35:65, v/v. The elute was monitored with the UV–vis detector at 210 nm with a flow rate of 1 mL/min. Calibration curve was linear over the concentration range of 25–2000 ng/mL. The retention times of nateglinide and internal standard (gliclazide were 9.608 min and 11.821 min respectively. The developed RP-HPLC method can be successfully applied to the quantitative pharmacokinetic parameters determination of nateglinide in rabbit model. Keywords: HPLC, Nateglinide, Rabbit plasma, Pharmacokinetics

  5. Reversal of endothelial dysfunction in aorta of streptozotocin-nicotinamide-induced type-2 diabetic rats by S-Allylcysteine.

    Science.gov (United States)

    Brahmanaidu, Parim; Uddandrao, V V Sathibabu; Sasikumar, Vadivukkarasi; Naik, Ramavat Ravindar; Pothani, Suresh; Begum, Mustapha Sabana; Rajeshkumar, M Prasanna; Varatharaju, Chandrasekar; Meriga, Balaji; Rameshreddy, P; Kalaivani, A; Saravanan, Ganapathy

    2017-08-01

    Dietary measures and plant-based therapies as prescribed by native systems of medicine have gained attraction among diabetics with claims of efficacy. The present study investigated the effects of S-Allylcysteine (SAC) on body weight gain, glucose, insulin, insulin resistance, and nitric oxide synthase in plasma and argininosuccinate synthase (AS) and argininosuccinate lyase (ASL), lipid peroxides and antioxidant enzymes in aorta of control and streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. Changes in body weight, glucose, insulin, insulin resistance, and antioxidant profiles of aorta and mRNA expressions of nitric oxide synthase, AS, and ASL were observed in experimental rats. SAC (150 mg/kg b.w) showed its therapeutic effects similar to gliclazide in decreasing glucose, insulin resistance, lipid peroxidation, and increasing body weight; insulin, antioxidant enzymes, and mRNA levels of nitric oxide synthase, argininosuccinate synthase, and argininosuccinate lyase genes in STZ-NA rats. Histopathologic studies also revealed the protective nature of SAC on aorta. In conclusion, garlic and its constituents mediate the anti-diabetic potential through mitigating hyperglycemic status, changing insulin resistance by alleviating endothelial dysregulation in both plasma and tissues.

  6. Strychnos nux-vomica seeds: Pharmacognostical standardization, extraction, and antidiabetic activity

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    Rajesh Bhati

    2012-01-01

    Full Text Available Background: Strychnos nux-vomica, commonly known as kuchla, contains strychnine and brucine as main constituents. Minor alkaloids present in the seeds are protostrychnine, vomicine, n-oxystrychnine, pseudostrychnine, isostrychnine, chlorogenic acid, and a glycoside. Seeds are used traditionally to treat diabetes, asthma, aphrodisiac and to improve appetite. Objective: The present study was aimed to evaluate the various pharmacognostical characters and antidiabetic activity of S. nux-vomica seed. Materials and Methods: Pharmacognostical characters were performed as per the WHO guideline. Extraction was carried out in petroleum ether, chloroform, alcohol, hydroalcoholic, aqueous, and phytochemical constituents present in extracts were detected by different chemical tests. Among these extracts hydroalcoholic, aqueous extracts were evaluated for antidiabetic activity on the basis of extractive yield and phytoconstituents, in alloxan-induced diabetic rats using gliclazide as standard. Results: Various analytical values of S. nux-vomica extract were established. Phytoconstituents present in S. nux-vomica extracts were detected. Conclusion: S. nux-vomica extracts show antihyperglycemic activity in experimental animals.

  7. PENGARUH EKSTRAK ETANOL BIJI KLABET (Trigonella foenum- graecum L. TERHADAP KADAR GULA DARAH TIKUS NIDDM

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    Lucie Widowati

    2012-09-01

    Full Text Available Trigonella foenum-graecum L. (klabet is one of the Indonesian medicinal plants and can be used to decrease glucose blood level on sufferer of diabetic. The effect of hypoglycemic of klabet seed extract on albino male rats has been investigated. Hyper­glycemic was induced by alloxan tetrahydrate 125 mg/kg body weight. The doses of the klabet extract were administered orally during 3 days and 7 days. Plasma glucose level was measured by Tinder method. Decrease percentage of plasma glucose level in gliclazide 1.4 mg/200g body weight, klabet seed extract 140 (DI, 280 (DII and 560 (DIII mg/200g body weight after 3 days of administration were 26.2, 17.97, 17.21, 14.17 respectively and decrease percentage after 7 days of administration were 42.74, 41.22, 42.86, 34.77 res­pectively. The effect of hypoglycemic was observed on 140 mg/200g body weight and 280 mg/200g body weight (p>0.05.

  8. Outpatient management of steroid-induced hyperglycaemia and steroid-induced diabetes in people with lymphoproliferative disorders treated with intermittent high dose steroids

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    Jennifer Vidler

    2017-09-01

    Eighty-three people were diagnosed with a lymphoproliferative disorder, of whom 6 had known Type 2 diabetes. Fifty-three people without known diabetes were screened by HbA1c and random venous plasma glucose. All patients (n = 34 subsequently prescribed HDS checked capillary blood glucose (CBG pre-breakfast and pre-evening meal. Treatment algorithms used initiation and/or dose titration of gliclazide or human NPH insulin, aiming for pre-meal CBG 5–11 mmol/l. Type 2 diabetes was identified in 4/53 people screened (7.5%. Of 34 people treated with HDS, 17 (44% developed SIH/SID. All 7 people with Type 2 diabetes developed SIH and 3 required insulin. Of 27 people without known diabetes, 8 (30% developed SID and 1 required insulin. Pre-treatment HbA1c was higher in people who developed SID compared to those that did not (p = 0.002. This is the first report of a SID/SIH detection and treatment protocol for use in people with lymphoproliferative disorders receiving intermittent HDS, demonstrating its feasibility and safety.

  9. Clinical management of carbamazepine intoxication during anti-tubercular treatment: a case report

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    Massimo Calderazzo

    2015-06-01

    Full Text Available We describe a 67-year-old man with medical history of focal post-stroke seizure and type 2 diabetes mellitus treated with carbamazepine, clobazam, gliclazide, insulin glargine, and omeprazole we visited for the onset in the last 7 days of asthenia, cough with mucus, breathing difficulty, chest pain, and weight loss. After clinical and laboratory tests, pulmonary tuberculosis was diagnosed, and a treatment with isoniazid, ethambutol, pyrazinamide rifampicin, and pyridoxine was started. Therapeutic drug monitoring of tuberculosis treatment documented that all drugs were in normal therapeutic range. Four days after the beginning of the treatment, we documented the improvement of fever, and three days later the patient showed sleepiness, visual disorder and asthenia. Clinical and pharmacological evaluation suggested a carbamazepine toxicity probably related to a drug interaction (Drug Interaction Probability Scale score = 6. The impossibility to switch carbamazepine for another antiepileptic drug, due to a resistant form of seizure, induced the discontinuation of tuberculosis treatment, resulting in the normalization of serum carbamazepine levels in one day (10 µg/ml and in the worsening of fever, requiring a new clinical and pharmacological evaluation. The titration dosage of carbamazepine and its therapeutic drug monitoring allowed to continue the treatment with both antitubercular drugs and carbamazepine, without the development of adverse drug reactions. To date, tuberculosis treatment was stopped and clinical evaluation, radiology and microbiology assays documented the absence of tubercular infection and no seizures appeared (carbamazepine dosage 800 mg/bid; serum levels 9.5 µg/ml.

  10. Modulation of trichloroethylene in vitro metabolism by different drugs in human.

    Science.gov (United States)

    Cheikh Rouhou, Mouna; Haddad, Sami

    2014-08-01

    Toxicological interactions with drugs have the potential to modulate the toxicity of trichloroethylene (TCE). Our objective is to identify metabolic interactions between TCE and 14 widely used drugs in human suspended hepatocytes and characterize the strongest using microsomal assays. Changes in concentrations of TCE and its metabolites were measured by headspace GC-MS. Results with hepatocytes show that amoxicillin, cimetidine, ibuprofen, mefenamic acid and ranitidine caused no significant interactions. Naproxen and salicylic acid showed to increase both TCE metabolites levels, whereas acetaminophen, carbamazepine and erythromycin rather decreased them. Finally, diclofenac, gliclazide, sulphasalazine and valproic acid had an impact on the levels of only one metabolite. Among the 14 tested drugs, 5 presented the most potent interactions and were selected for confirmation with microsomes, namely naproxen, salicylic acid, acetaminophen, carbamazepine and valproic acid. Characterization in human microsomes confirmed interaction with naproxen by competitively inhibiting trichloroethanol (TCOH) glucuronidation (Ki=2.329 mM). Inhibition of TCOH formation was also confirmed for carbamazepine (partial non-competitive with Ki=70 μM). Interactions with human microsomes were not observed with salicylic acid and acetaminophen, similar to prior results in rat material. For valproic acid, interactions with microsomes were observed in rat but not in human. Inhibition patterns were shown to be similar in human and rat hepatocytes, but some differences in mechanisms were noted in microsomal material between species. Next research efforts will focus on determining the adequacy between in vitro observations and the in vivo situation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Rapid identification of illegal synthetic adulterants in herbal anti-diabetic medicines using near infrared spectroscopy

    Science.gov (United States)

    Feng, Yanchun; Lei, Deqing; Hu, Changqin

    We created a rapid detection procedure for identifying herbal medicines illegally adulterated with synthetic drugs using near infrared spectroscopy. This procedure includes a reverse correlation coefficient method (RCCM) and comparison of characteristic peaks. Moreover, we made improvements to the RCCM based on new strategies for threshold settings. Any tested herbal medicine must meet two criteria to be identified with our procedure as adulterated. First, the correlation coefficient between the tested sample and the reference must be greater than the RCCM threshold. Next, the NIR spectrum of the tested sample must contain the same characteristic peaks as the reference. In this study, four pure synthetic anti-diabetic drugs (i.e., metformin, gliclazide, glibenclamide and glimepiride), 174 batches of laboratory samples and 127 batches of herbal anti-diabetic medicines were used to construct and validate the procedure. The accuracy of this procedure was greater than 80%. Our data suggest that this protocol is a rapid screening tool to identify synthetic drug adulterants in herbal medicines on the market.

  12. Diabetes and Ramadan: an update on use of glycemic therapies during fasting.

    Science.gov (United States)

    Ahmed, Mohamed H; Abdu, Tarig A M

    2011-01-01

    The fasting of Ramadan is observed by a large proportion of Muslims with diabetes. Recommendations for the management of diabetes during Ramadan were last published in 2005 by the American Diabetes Association. Several studies in this field have since been published, some addressing the use of new pharmacological agents in managing diabetes during Ramadan. The incritin memetics are potentially safe during Ramadan; the DPP4 inhibitors vildagliptin and sitagliptin provide an effective and safe therapeutic option, administered either alone or in combination with metformin or sulfonylureas. There are no published studies on the use of GLP-1 receptor agonists during Ramadan. Among the sulfonylureas, gliclazide MR (modified release) and glimepride can be safely used during Ramadan, but glibenclamide should be avoided due to the associated risk of hypoglycemia. In selected patients with type 1 and type 2 diabetes, the long-acting insulin analogues glargine and detemir, as well as the premixed insulin analogues, can be used with minimal risk of metabolic derangement or hypoglycemia; the risk is higher in type 1 diabetes. Insulin pumps can potentially empower patients with diabetes and enable safe fasting during the month of Ramadan. Further clinical trials are needed to evaluate the safety and efficacy of new antidiabetic agents and new diabetes-related technologies during Ramadan.

  13. Determination of Doxorubicin in Stealth Hyalurionic Acid-Based Nanoparticles in Rat Plasma by the Liquid-Liquid Nanoparticles-Breaking Extraction Method: Application to a Pharmacokinetic Study.

    Science.gov (United States)

    Han, Xiaopeng; Wei, Wei; Zhong, Lu; Luo, Cong; Wu, Chunnuan; Jiang, Qikun; Sun, Jin

    2016-09-01

    An efficient extraction of doxorubicin (Dox) from homemade stealth hyalurionic acid (HA)-based nanoparticles (NPs) in rat plasma could not be performed by previously published methods. Therefore, we attempted to establish the novel NPs-breaking and UPLC-MS-MS method for evaluating the pharmacokinetic profiles of the homemade stealth HA NPs in rats. The pretreatment method of plasma samples used the liquid-liquid extraction method with isopropyl alcohol as NPs-breaking and protein-precipitating solvents, and the NPs-breaking efficiency of isopropyl alcohol was as high as 97.2%. The analyte and gliclazide (internal standard) were extracted from plasma samples with isopropyl alcohol and were separated on UPLC BEH C18 with a mobile phase consisting of methanol and water (containing 0.1% formic acid). The method demonstrated good linearity at the concentrations ranging from 5 to 5,000 ng/mL. The intra- and interday relative standard deviations were >10%. Finally, the method was successfully applied to a pharmacokinetic study of homemade stealth HA-based NPs in rats following intravenous administration. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Antidiabetic Effects of Add-On Gynostemma pentaphyllum Extract Therapy with Sulfonylureas in Type 2 Diabetic Patients

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    V. T. T. Huyen

    2012-01-01

    Full Text Available Aims. To investigate the antidiabetic effect of the traditional Vietnamese herb Gynostemma pentaphyllum (GP together with sulfonylurea (SU in 25 drug-naïve type 2 diabetic patients. Methods. After 4-week treatment with gliclazide (SU, 30 mg daily, all patients were randomly assigned into 2 groups to add on GP extract or placebo extract, 6 g daily, during eight weeks. Results. After 4-week SU treatment, fasting plasma glucose (FPG and HbA1C decreased significantly (P<0.001. FPG was further reduced after add-on therapy with 2.9 ± 1.7 and 0.9 ± 0.6 mmol/L in the GP and placebo groups, respectively (P<0.001. Therapy with GP extract also reduced 30- and 120-minute oral glucose tolerance test postload values. HbA1C levels decreased approximately 2% units in the GP group compared to 0.7% unit in the placebo group (P<0.001. Conclusion. GP extract in addition to SU offers an alternative to addition of other oral medication to treat type 2 diabetic patients.

  15. Place of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: A consensus statement

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    Sanjay Kalra

    2015-01-01

    Full Text Available Since their introduction in clinical practice in the 1950′s, Sulfonylureas (SUs have remained the main-stay of pharmacotherapy in the management of type 2 diabetes. Despite their well-established benefits, their place in therapy is inappropriately being overshadowed by newer therapies. Many of the clinical issues associated with the use of SUs are agent-specific, and do not pertain to the class as such. Modern SUs (glimepiride, gliclazide MR are backed by a large body of evidence, experience, and most importantly, outcome data, which supports their role in managing patients with diabetes. Person-centred care, i.e., careful choice of SU, appropriate dosage, timing of administration, and adequate patient counseling, will ensure that deserving patients are not deprived of the advantages of this well-established class of anti-diabetic agents. Considering their efficacy, safety, pleiotropic benefits, and low cost of therapy, SUs should be considered as recommended therapy for the treatment of diabetes in South Asia. This initiative by SAFES aims to encourage rational, safe and smart prescription of SUs, and includes appropriate medication counseling.

  16. Role of oral hypoglycemic agents in the management of type 2 diabetes mellitus during Ramadan

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    Mir Iftikhar Bashir

    2012-01-01

    Full Text Available It is obligatory for all adult Muslims to observe fast during the holy month of Ramadan, but sick individuals including those with diabetes mellitus are exempted from the duty of fasting. Specific medical advice must be provided to individual patients concerning the potential risks they must accept if they decide to fast. Any alteration in medications deemed necessary to provide an effective and safe antidiabetic regimen should be instituted well before the start of Ramadan. Diet-controlled patients and those well controlled on insulin sensitizers have low risk of hypoglycemia and may safely fast with some modification in the timing of the doses. Newer generation sulfonylureas (gliclazide MR and glimepiride have reasonable safety profile during Ramadan fasting and are economical options for a large number of diabetics worldwide, especially in the developing countries; older, long acting sulfonylureas like glibenclamide and chlorpropamide should be avoided during fasting. Oral DPP-IV inhibitors are important substitutes to sulfonylureas for patients with diabetes mellitus during fasting owing to their glucose-dependent mechanism of action, efficacy, and tolerability. This group of drugs causes a moderate A1c reduction, are weight neutral, and have a very low risk of hypoglycemia. Short-acting insulin secretagogues are an option in the subset of fasting diabetic patients who have predominantly post-prandial hyperglycemia.

  17. Role of oral hypoglycemic agents in the management of type 2 diabetes mellitus during Ramadan

    Science.gov (United States)

    Bashir, Mir Iftikhar; Pathan, Md Faruque; Raza, Syed Abbas; Ahmad, Jamal; Khan, A. K. Azad; Ishtiaq, Osama; Sahay, Rakesh K.; Sheikh, Aisha; Zargar, Abdul Hamid

    2012-01-01

    It is obligatory for all adult Muslims to observe fast during the holy month of Ramadan, but sick individuals including those with diabetes mellitus are exempted from the duty of fasting. Specific medical advice must be provided to individual patients concerning the potential risks they must accept if they decide to fast. Any alteration in medications deemed necessary to provide an effective and safe antidiabetic regimen should be instituted well before the start of Ramadan. Diet-controlled patients and those well controlled on insulin sensitizers have low risk of hypoglycemia and may safely fast with some modification in the timing of the doses. Newer generation sulfonylureas (gliclazide MR and glimepiride) have reasonable safety profile during Ramadan fasting and are economical options for a large number of diabetics worldwide, especially in the developing countries; older, long acting sulfonylureas like glibenclamide and chlorpropamide should be avoided during fasting. Oral DPP-IV inhibitors are important substitutes to sulfonylureas for patients with diabetes mellitus during fasting owing to their glucose-dependent mechanism of action, efficacy, and tolerability. This group of drugs causes a moderate A1c reduction, are weight neutral, and have a very low risk of hypoglycemia. Short-acting insulin secretagogues are an option in the subset of fasting diabetic patients who have predominantly post-prandial hyperglycemia. PMID:22837904

  18. Calcium-antagonists and islet function. V. Effect of R33711

    Energy Technology Data Exchange (ETDEWEB)

    Malaisse, W J; Sener, A; Devis, G; Somers, G [Brussels Univ. (Belgium). Lab. of Experimental Medicine

    1976-11-01

    R33711, a new drug with presumed potent calcium-antagonistic property, was found to suppress the insulinotropic action of glucose und gliclazide but not that of theophylline. A 0.2 ..mu..M concentration of R33711 was sufficient to abolish glucose-induced insulin release. At this concentration, R33711 inhibited the net uptake of /sup 45/Ca/sup 2 +/ by isolated islets, whether in the absence or presence of either glucose or sulfonylurea. In the isolated islets, R33711 failed to affect the glucose-stimulated production of lactate, the rate of /sup 45/Ca/sup 2 +/ efflux, the inhibitory action of glucose upon such an efflux and its increase in response to theophylline. These data are compatible with the view that R33711 inhibits entry of Ca/sup 2 +/ into the B-cell and that integrity of such an inward cationic movement usually plays a permissive role in the maintenance of the Ca/sup 2 +/-dependent insulin secretory process.

  19. Purposeful search of hypoglycemic agents among N-arylcarbamides and N-arylsulfamides of [2-(3-R-1Н-[1,2,4]triazole-5-ylphenyl]amines

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    S. V. Kholodnyak

    2015-08-01

    Full Text Available Aim. Formation of N-arylcarbamides and N-arylsulfamides as result of interaction of 2-(3-R-1Н-[1,2,4]triazole-5-ylphenyl]amines with electrophilic reagents (arylisocyanates and arylsulfonylchlorides is described in presented article. The optimal conditions for mentioned reactions have been proposed. Methods and results. It has been evaluated that N-arylcarbamides of 2-(3-aryl-1H-1,2,4-triazole-5-ylphenyl]amines while heating over 90°C in glacial acetic acid undergo cyclisation followed by formation of corresponding 2-aryl-[1,2,4]triazolo[1,5-c]quinazoline-5(6Н-ones. Purity and structure of synthesized compounds has been proved by elemental analysis, 1H NMR-, chromato-mass and mass-spectra. Conclusion. It has been established, that compound 2.1 during evaluation of specific pharmacologic activities on oral glucose tolerance test (OGTT, rapid insulin and adrenaline test models exhibited action which is comparable to activities of reference-drugs «Metformin» and «Gliclazide».

  20. Multi-residue analysis method for analysis of pharmaceuticals using liquid chromatography-time of flight/mass spectrometry (LC-TOF/MS) in water sample

    Science.gov (United States)

    Al-Qaim, Fouad Fadhil; Abdullah, Md Pauzi; Othman, Mohamed Rozali

    2013-11-01

    In this work, a developed method using solid - phase extraction (SPE) followed by liquid chromatography - time of flight mass spectrometry (LC-ESI-TOF/MS) was developed and validated for quantification and confirmation of eleven pharmaceuticals with different therapeutic classes in water samples, Malaysia. These compounds are caffeine (CAF), prazosin (PRZ), enalapril (ENL), carbamazepine (CBZ), nifedipine (NFD), levonorgestrel (LNG), simvastatin (SMV), hydrochlorothiazide (HYD), gliclazide (GLIC), diclofenac-Na (DIC-Na) and mefenamic acid (MEF). LC was performed on a Dionex Ultimate 3000/LC 09115047 (USA) system. Chromatography was performed on a Thermo Scientific C18 (250 mm × 2.1 mm, i.d.: 5μm) column. Several parameters were optimised such as; mobile phase, gradient elution, collision energy and solvent elution for extraction of compounds from water. The recoveries obtained ranged from 30-148 % in river water. Five pharmaceutical compounds were detected in the surface water samples: caffeine, prazosin, enalpril, diclofenac-Na and mefenamic acid. The developed method is precise and accepted recoveries were got. In addition, this method is suitable to identify and quantify trace concentrations of pharmaceuticals in surface water.

  1. Quantitative Evaluation of Compliance with Recommendation for Sulfonylurea Dose Co-Administered with DPP-4 Inhibitors in Japan

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    Motonobu Sakaguchi

    2012-09-01

    Full Text Available After the launch of dipeptidyl peptidase-4 (DPP-4, a new oral hypoglycemic drug (OHD, in December 2009, severe hypoglycemia cases were reported in Japan. Although the definite cause was unknown, co-administration with sulfonylureas (SU was suspected as one of the potential risk factors. The Japan Association for Diabetes Education and Care (JADEC released a recommendation in April 2010 to lower the dose of three major SUs (glimepiride, glibenclamide, and gliclazide when adding a DPP-4 inhibitor. To evaluate the effectiveness of this risk minimization action along with labeling changes, dispensing records for 114,263 patients prescribed OHDs between December 2008 and December 2010 were identified in the Nihon-Chouzai pharmacy claims database. The adherence to the recommended dosing of SU co-prescribed with DPP-4 inhibitors increased from 46.3% before to 63.8% after the JADEC recommendation (p < 0.01 by time-series analysis, while no change was found in those for SU monotherapy and SU with other OHD co-prescriptions. The adherence was significantly worse for those receiving a glibenclamide prescription. The JADEC recommendation, along with labeling changes, appeared to have a favorable effect on the risk minimization action in Japan. In these instances, a pharmacy claims database can be a useful tool to evaluate risk minimization actions.

  2. A dizygotic twin pregnancy in a MODY 3-affected woman.

    Science.gov (United States)

    Bitterman, O; Iafusco, D; Torcia, F; Tinto, N; Napoli, A

    2016-10-01

    MODY diabetes includes rare familiar forms due to genetic mutations resulting in β-cell dysfunction. MODY 3 is due to mutations in the gene transcription factor HNF-1α, with diabetes diagnosis in adolescence or early adult life. Few data are available about MODY 3 in pregnancy. A 36-year-old Italian woman came to our unit at the 5th week of pregnancy. She was diagnosed with diabetes at 18 years, with negative autoimmunity and a strong familiarity for diabetes. She was treated with gliclazide and metformin. She had a previous pregnancy in which she was treated with insulin, giving birth at 38 weeks to a 3.210 kg baby girl, who showed neonatal hypoglycemia. We switched her to insulin treatment according to guidelines. We asked for genetic molecular testing, resulting in a HNF-1α gene mutation. A US examination at 7 weeks revealed a twin, bicorial, biamniotic pregnancy. At 37 weeks of gestation, she gave birth to two normal-weight baby girls; only one showed neonatal hypoglycemia and a genetic test revealed that she was affected by HNF-1α gene mutation. Subsequently, entire family of the woman was tested, showing that the father, the sister and the first daughter had the same HNF-1α mutation. A MODY 3 foetus needs a near-normal maternal glycemic control, because the exposure to intrauterine hyperglycemia can lead to an earlier age of diabetes onset. Neonatal hypoglycemia is generally observed in MODY 1 infants, but it is possible to hypothesize that some HNF-1α mutations could lead to a functionally impaired protein that might dysregulate HNF-4α expression determining hypoglycemia.

  3. Rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes): A multicenter retrospective nationwide Italian study and crowdsourcing opportunity.

    Science.gov (United States)

    Fadini, G P; Zatti, G; Consoli, A; Bonora, E; Sesti, G; Avogaro, A

    2017-12-01

    Randomized controlled trials (RCTs) in the field of diabetes have limitations inherent to the fact that design, setting, and patient characteristics may be poorly transferrable to clinical practice. Thus, evidence from studies using routinely accumulated clinical data are increasingly valued. We herein describe rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes), a multicenter retrospective nationwide study conducted at 50 specialist outpatient clinics in Italy and promoted by the Italian Diabetes Society. The primary objective of the study is to describe the baseline clinical characteristics (particularly HbA1c) of patients initiated on dapagliflozin from marketing authorization approval to the end of 2016. Secondary and exploratory objectives will evaluate the changes in glycaemic and extraglycaemic efficacy parameters after initiation of dapagliflozin or after initiation of comparator glucose lowering medications (DPP-4 inhibitors, gliclazide extended release, and long-acting GLP-1 receptor agonists). An automated software will extract relevant data from the same electronic chart system at all centres, thereby minimizing data treatment and human intervention. The study is expected to collect an enormous dataset of information on dapagliflozin- and comparator-using patients. After study completion, the Italian Diabetes Society will launch an open crowdsourcing call on the DARWIN-T2D database, challenging diabetes researchers to apply their ideas and approaches to address new unmet needs and knowledge gaps in diabetes. We believe this will move DARWIN-T2D to the next generation of real world studies. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  4. Efficacy of vildagliptin versus sulfonylureas as add-on therapy to metformin: comparison of results from randomised controlled and observational studies.

    Science.gov (United States)

    Ahrén, Bo; Mathieu, Chantal; Bader, Giovanni; Schweizer, Anja; Foley, James E

    2014-07-01

    Randomised control trials (RCTs) do not always reflect real-life outcomes for glucose-lowering drugs. In this work we compared RCT and real-life data on the efficacy of the dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin or sulfonylureas when added to metformin. Data were pooled from five RCTs examining vildagliptin (n = 2,788) and sulfonylureas (glimepiride [n = 1,259] or gliclazide [n = 433]), added to metformin. For real-life conditions, data were extracted from an observational study examining vildagliptin (n = 7,002) or sulfonylureas (n = 3,702), added to metformin monotherapy. Linear regression analyses were performed between the baseline HbA1c and the change in HbA1c (Δ HbA1c) after 24 weeks. Baseline HbA1c correlated to Δ HbA1c (r (2) = 0.36, slope = -0.54 [95% CI -0.55, -0.53; p vildagliptin, the slope was virtually identical in the observational study and the RCTs (interaction coefficient = 0.024, p = 0.175). For any given baseline HbA1c, Δ HbA1c with sulfonylureas was smaller in real life than in RCTs, whereas Δ HbA1c with vildagliptin was the same. When comparing RCT to real-life data, the decrease in HbA1c from baseline with sulfonylurea treatment is smaller in real life than in RCTs, whereas the reduction with vildagliptin is essentially the same, suggesting that the full power of treatment is retained in real life for vildagliptin but not for sulfonylureas, possibly due to fear of hypoglycaemia.

  5. β-Cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore extract against alloxan-induced oxidative stress via regulation of apoptosis and reactive oxygen species (ROS).

    Science.gov (United States)

    Bahar, Entaz; Akter, Kazi-Marjahan; Lee, Geum-Hwa; Lee, Hwa-Young; Rashid, Harun-Or; Choi, Min-Kyung; Bhattarai, Kashi Raj; Hossain, Mir Mohammad Monir; Ara, Joushan; Mazumder, Kishor; Raihan, Obayed; Chae, Han-Jung; Yoon, Hyonok

    2017-03-29

    Medicinal plants are becoming more popular in the treatment of various diseases because of the adverse effects of the current therapy, especially antioxidant plant components such as phenols and flavonoids have a protective role against oxidative stress-induced degenerative diseases like diabetes. Thus, the purpose of this study was to investigate β-cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore. The in-vitro study was conducted by the pancreatic β-cell culture and α-amylase inhibition technique which includes two methods, namely starch-iodine method and 3,5-dinitrosalicylic acid (DNSA) method. On the other hand, the in-vivo study was performed by oral glucose tolerance test (OGTT) method and alloxan-induced diabetes method by using Wistar albino rat. At the end pancreatic specimens were removed and processed for histopathological study. The plant extract showed significant (*p < 0.05, **p < 0.01) effect on hyperglycemia as compared to standard (Gliclazide) in OGTT. The plant extract showed efficient protection activity of pancreatic β-cell from cell death in INS-1 cell line by significantly reduced (*p < 0.05, **p < 0.01) the levels alloxan-induced apoptosis and intracellular reactive oxygen species (ROS) accumulation. In addition, the plant extract showed a significant (*p < 0.05, **p < 0.01) effect on hyperglycemia by increases in percent of β-cells present in each islet (45% - 60%) compared to the diabetic group. The result showed that C. crepidioides had β-cell protection and antidiabetic activities in pancreatic β-cell culture and Wistar albino rat.

  6. Parsimonious model for blood glucose level monitoring in type 2 diabetes patients.

    Science.gov (United States)

    Zhao, Fang; Ma, Yan Fen; Wen, Jing Xiao; DU, Yan Fang; Li, Chun Lin; Li, Guang Wei

    2014-07-01

    To establish the parsimonious model for blood glucose monitoring in patients with type 2 diabetes receiving oral hypoglycemic agent treatment. One hundred and fifty-nine adult Chinese type 2 diabetes patients were randomized to receive rapid-acting or sustained-release gliclazide therapy for 12 weeks. Their blood glucose levels were measured at 10 time points in a 24 h period before and after treatment, and the 24 h mean blood glucose levels were measured. Contribution of blood glucose levels to the mean blood glucose level and HbA1c was assessed by multiple regression analysis. The correlation coefficients of blood glucose level measured at 10 time points to the daily MBG were 0.58-0.74 and 0.59-0.79, respectively, before and after treatment (Pblood glucose levels measured at 6 of the 10 time points could explain 95% and 97% of the changes in MBG before and after treatment. The three blood glucose levels, which were measured at fasting, 2 h after breakfast and before dinner, of the 10 time points could explain 84% and 86% of the changes in MBG before and after treatment, but could only explain 36% and 26% of the changes in HbA1c before and after treatment, and they had a poorer correlation with the HbA1c than with the 24 h MBG. The blood glucose levels measured at fasting, 2 h after breakfast and before dinner truly reflected the change 24 h blood glucose level, suggesting that they are appropriate for the self-monitoring of blood glucose levels in diabetes patients receiving oral anti-diabetes therapy. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  7. Balanites aegyptiaca ameliorates insulin secretion and decreases pancreatic apoptosis in diabetic rats: Role of SAPK/JNK pathway.

    Science.gov (United States)

    Hassanin, Kamel M A; Mahmoud, Mohamed O; Hassan, Hossam M; Abdel-Razik, Abdel-Razik H; Aziz, Lourin N; Rateb, Mostafa E

    2018-06-01

    SAPK-JNK pathway performs a significant role in the pathogenesis of type 2 diabetes. Balanites aegyptiaca (BA) is used as an anti-diabetic agent in folk medicine however its hypoglycemic mechanism is not fully elucidated. The current study aimed to evaluate the effect of crude extract, butanol, and dichloromethane fractions from BA on the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK-JNK) pathway in experimental diabetic rats. Six groups of male Wistar rats were included: normal control, diabetic, diabetic rats treated with crude, butanol or dichloromethane fraction from BA (50 mg/kg BW) and diabetic rats treated with gliclazide as a reference drug for one month. Our results suggested a protective role of treatment of diabetic rats with BA against oxidative stress-induced SAPK-JNK pathway. Moreover, BA treatment produced a reduction in plasma glucose, HbA 1c , lactic acid, lipid profile, malondialdehyde levels and produced an increase in insulin, reduced glutathione levels, catalase and superoxide dismutase activities compared with untreated diabetic rats. Moreover, it decreased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase 1, protein 53 and increased insulin receptor substrate 1 in rat pancreas while it increased glucose transporter 4 in rat muscle. Analysis of BA extracts by LC-HRMS revealed the presence of different saponins with reported hypoglycemic effect. In conclusion, BA exerted hypoglycemic, hypolipidemic, insulinotropic and antioxidant effects. Additionally, it reduced apoptosis in pancreatic β-cells and increased glucose uptake in muscle. These results suggest that the hypoglycemic effect of BA is due to the inhibition of the SAPK-JNK pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  8. Simultaneous determination of lercanidipine, benazepril and benazeprilat in plasma by LC-MS/MS and its application to a toxicokinetics study.

    Science.gov (United States)

    Chen, Keguang; Zhang, Jing; Liu, Sha; Zhang, Dujuan; Teng, Yanni; Wei, Chunmin; Wang, Benjie; Liu, Xiaoyan; Yuan, Guiyan; Zhang, Rui; Zhao, Wenjing; Guo, Ruichen

    2012-06-15

    We aim to develop a rapid, simple, sensitive and specific LC-MS/MS method for the simultaneous quantification of lercanidipine, benazepril and benazeprilat in plasma. It is performed on the Agilent 6410 LC-MS/MS under the multiple-reaction monitoring (MRM) mode with electrospray ionization. Gliclazide was used as the internal standard (IS). Analytes and IS were extracted from plasma by solid-phase extraction. The reconstituted samples were chromatographed on a Diamond C₁₈(150 mm × 4.6 mm, 5 μm) column. The mobile phase was composed of 0.1% acetic acid-acetonitrile (50:50, v/v), with gradient flow rates: 0.6 mL/min (0-4.55 min); 4.55-4.65 min, 1 mL/min; 1 mL/min (4.65-9.5 min); 9.5-9.6 min, 0.6 mL/min; 0.6 mL/min (9.6-10 min). Method validation demonstrated that the method was of satisfactory specificity, sensitivity, precision and accuracy in linear ranges of 1-2000 ng/mL for lercanidipine, 1-2000 ng/mL for benazepril and 1-1600 ng/mL for benazeprilat, respectively. The precision (RSD%) was better than 15, and the lower limit of quantitation was identifiable and reproducible at 1 ng/mL for the three analytes. The plasma samples were stable after being stored for more than 60 days and after two freeze-thaw cycles (-20 to -25 °C). It is demonstrated that this method was successfully applied to samples from a toxicokinetics study of a compound of lercanidipine and benazepril in beagle dogs. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Generic substitution of antidiabetic drugs in the elderly does not affect adherence

    Directory of Open Access Journals (Sweden)

    Francesco Trotta

    2014-12-01

    Full Text Available INTRODUCTION: The possibility that variation in packaging and pill appearance may reduce adherence is a reason for concern, especially for chronic diseases. The objectives of the study were to quantify the extent of switches between generic antidiabetics and to verify whether switching between different products of the same substance affects adherence. MATERIALS AND METHODS: All elderly residents of the Umbria Region who received at least 2 prescriptions of antidiabetics in 2010 and 2011 were included in the study. Switching was defined as the dispensing of two different products of the same substance in a series of two prescriptions. Single and multiple switchers were identified according to the number of switches during 2011. Switching relevant to the three off-patent substances with generic use ≥ 5% (metformin, gliclazide and repaglinide was quantified. The effect of switching on adherence, defined as the proportion of days in 2011 covered by prescriptions (Medication Possession Ratio, MPR, was estimated. RESULTS: Among the 15 964 patients receiving antidiabetics (14.4% of the elderly population 9211 were prescribed at least one of the generic substances. Of these patients, 23.3% experienced a single switch and 15.7% were multiple switchers (61.0% never switched. The proportion of multiple switchers increased with the number of prescriptions, reaching 26% among patients with ≥ 11 prescriptions. MPR was 62%, 62% and 72%, respectively among non-switchers, single and multiple switchers. CONCLUSIONS: In elderly patients treated with antidiabetics, the substitution between branded and unbranded products (as well as between generics of the same substance, did not negatively affect adherence.

  10. Effects of vildagliptin versus saxagliptin on daily acute glucose fluctuations in Chinese patients with T2DM inadequately controlled with a combination of metformin and sulfonylurea.

    Science.gov (United States)

    Xiaoyan, Chen; Jing, Wang; Xiaochun, Huang; Yuyu, Tan; Shunyou, Deng; Yingyu, Fu

    2016-06-01

    Objective The present study aimed to compare the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin and saxagliptin on 24 hour acute glucose fluctuations in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with a combination of metformin and sulfonylurea. Research design and methods This was a 24 week, prospective, randomized, open-label, active-controlled study. Patients (N = 73) with T2DM who had inadequate glycemic control (HbA1c 7.0%-10.0%) with a stable dosage of metformin plus gliclazide for more than 3 months were randomized to receive either vildagliptin 50 mg twice daily (BID, n = 37) or saxagliptin 5 mg once daily (QD, n = 36). Change in mean amplitude of glycemic excursions (MAGE) was assessed at the end of 24 weeks. Results At baseline, the mean (±SD) age was 62.9 ± 6.55 years, disease duration was 7.0 ± 2.33 years, and HbA1c was 8.4 ± 0.68%. After 24 weeks of treatment, the MAGE decreased from 5.81 ± 1.16 mmol/L to 4.06 ± 0.86 mmol/L (pvildagliptin group and from 5.66 ± 1.14 mmol/L to 4.79 ± 1.25 mmol/L (p = 0.003) in the saxagliptin group. The mean change in MAGE in the vildagliptin group was significantly greater than that in the saxagliptin group (1.74 ± 0.48 mmol/L vs. 0.87 ± 0.40 mmol/L, pvildagliptin and saxagliptin groups, was 1.22 ± 0.40% and 1.07 ± 0.36%, respectively, with no significant difference between the groups (p = 0.091). The overall safety and tolerability of vildagliptin and saxagliptin were similar. The limitations of the study were a small number of patients and open-label administration of the study drug. Conclusion Vildagliptin produced a significantly greater reduction in acute glucose fluctuations compared with saxagliptin when added to a dual combination of metformin and sulfonylurea in Chinese patients with T2DM. Chinese clinical trial registration number ChiCTR-TRC-13003858.

  11. Efficacy and safety of hydroxychloroquine in the treatment of type 2 diabetes mellitus: a double blind, randomized comparison with pioglitazone.

    Science.gov (United States)

    Pareek, Anil; Chandurkar, Nitin; Thomas, Nihal; Viswanathan, Vijay; Deshpande, Alaka; Gupta, O P; Shah, Asha; Kakrani, Arjun; Bhandari, Sudhir; Thulasidharan, N K; Saboo, Banshi; Devaramani, Shashidhar; Vijaykumar, N B; Sharma, Shrikant; Agrawal, Navneet; Mahesh, M; Kothari, Kunal

    2014-07-01

    To compare efficacy and safety of hydroxychloroquine with pioglitazone in type 2 diabetes mellitus (T2DM). This double-blind study randomized 267 uncontrolled type 2 diabetes patients (HbA1c ≥7.5% and ≤11.5%), post 3 months' treatment with glimepiride/gliclazide and metformin, to additionally receive hydroxychloroquine 400 mg/day (n = 135) or pioglitazone 15 mg/day (n = 132) for 24 weeks. Efficacy was assessed by changes in HbA1c, fasting (FBG) and post-prandial (PPG) blood glucose at Week 12 and Week 24. At Week 12 and Week 24, HbA1c, FBG and PPG significantly reduced from baseline in both groups. Mean reduction in glycemic parameters at Week 12 (HbA1c: -0.56% vs -0.72%, p = 0.394; FBG: -0.99 mmol/L vs -1.05 mmol/L, p = 0.878; PPG: -1.93 mmol/L vs -1.52 mmol/L, p = 0.423) and Week 24 (HbA1c: -0.87% vs -0.90%, p = 0.909; FBG: -0.79 mmol/L vs -1.02 mmol/L, p = 0.648; PPG: -1.77 mmol/L vs -1.36 mmol/L, p = 0.415) was not significantly different between the hydroxychloroquine and pioglitazone groups. Change in total cholesterol (TC) and LDL-C was significant in favor of hydroxychloroquine (TC: -0.37 mmol/L vs 0.03 mmol/L, p = 0.002; LDL-C: -0.23 mmol/L vs 0.09 mmol/L, p = 0.003). Triglycerides significantly reduced in both groups at Week 24. Mean HDL-C remained unchanged. Study treatments were well tolerated. With favorable effects on glycemic parameters and lipids, hydroxychloroquine may emerge as well tolerated therapeutic option for T2DM. The sample size for this study was small. However, based on the encouraging results of this proof-of-concept study, longer duration studies in larger population can be conducted to further confirm these findings. TRIAL REGISTRATION DETAILS: Clinical Trial Registry-India URL: http://ctri.nic.in, Registration Number: CTRI/2009/091/001036.

  12. [A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

    Science.gov (United States)

    Ozawa, Hikaru; Murai, Yuriko; Ozawa, Terutaka

    2003-01-01

    recombinant products prevailed throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin aspart) appeared in 2001. These are applied for after-meal glycosmia owing to their ultrarapid onset of activity. Self-injection by DM patients was legalized in 1981. To make the infection technique sure and easy, cartridge (pen-type) and disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic drugs: Instead of the exclusive parenteral usage of insulins, there was also demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55, was used for DM clinically in 1955 in Germany. But it was soon withdrawn because of its antibacterial action. This led to the development of various SU groups. Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999) appeared as the second-generation SUs. These were used orally for Type 2 diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU appears to act by increasing the sensitivity of b-cells, which secrete insulin. BG probably exerts by increasing glucose transport across the membranes of target organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e., acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after meals by decreasing glucose absorption. Thiazolidinedione compounds, such as troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing the insulin sensitivity of the target tissues. These are useful for Type 2 DM patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in 2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D-phenylalanine derivative acting similar to SUs, is useful orally for after