Gliclazide In Type Research Articles

Free Radical Scavenging Activity of Gliclazide in Type 2 Diabetic Mellitus Patients

To evaluate the effects of 8 weeks of gliclazide therapy on serum glucose level and serum malondialdehyde (MDA) as a marker of lipid peroxidation in newly diagnosed type 2 diabetes mellitus (T2DM) patients. Thirty newly diagnosed T2DM patients were participated in the study (15 males and 15 females) with mean age of (47.55+-8.46) years .A thirty healthy subjects (15 male and 15 females ) of matching age were also recruited in the study as control group. Both groups were matched regarding age, sex and BMI. Fasting serum glucose (FSG) concentration was estimated using a kit supplied by Biocon (Germany). Serum MDA was measured using thiobarbituric acid (TBA) chemical assay method. Showed that T2DM patients having a significant rise in marker of lipid peroxidation MDA and FSG before starting treatment as compared with the control group. After 8 weeks of gliclazide monotherapy there was a significant reduction in both FSG and MDA level. Gliclazide having free radical scavenger properties showed from the decrease in lipid peroxidation in addition to its hypoglycemic effects

The Position of Gliclazide in the Evolving Landscapes and Disease Continuum of T2DM: A Collaborative Delphi Survey-Based Consensus fromIndia.

IntroductionThis Delphi study aims to provide evidence-based expert opinion on the usage and current position of gliclazide in type 2 diabetes mellitus (T2DM) management in India.MethodsThe single interaction modified Delphi-based methodology was used to collect opinions on gliclazide usage and its position in diabetes management from 338 endocrinologists/diabetologists who have had clinical experience with gliclazide. Participants, using a 9-point scale, were asked to rate eight statements comprising a total of 52 items on the related topics.ResultsThe Delphi consensus suggests that in drug-naïve patients with T2DM, intolerant to metformin or in whom metformin is contraindicated, dual therapy of gliclazide/gliclazide-modified release (MR) should be considered along with a dipeptidyl peptidase 4 (DPP4) inhibitor if glycated hemoglobin A1c level is greater than 7.5% and with insulin if the A1c level is greater than 9%. If the patients are inadequately controlled with metformin (A1c greater than 6.5% after 3 months of therapy), gliclazide/gliclazide-MR shall be added on to the treatment regimen to achieve greater and sustained reductions in A1c levels. However, it was not preferred over other antidiabetic classes in such clinical settings except alpha-glucosidase inhibitors (AGI). Early addition of gliclazide/gliclazide-MR shall be preferred over the up-titration of metformin beyond half-maximal dose for effective management of T2DM. Gliclazide/gliclazide-MR can be used safely in patients with diabetes and cardiovascular and chronic kidney disease. It can be used in older patients with T2DM as it does not have active metabolites and has a low risk of hypoglycemia.ConclusionThe expert panel proposed consideration of monotherapy or dual therapy of gliclazide as an ideal choice in patients with T2DM because of its efficacy, long-term glycemic control, favorable renal outcomes, cardiovascular safety, and an optimal safety profile.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01002-4.

The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve hard renal outcomes in type 2 diabetes. This is possibly explained by the fact that SGLT2i normalize the measured glomerular filtration rate (mGFR) by increasing renal vascular resistance, as was shown in young people with type 1 diabetes and glomerular hyperfiltration. Therefore, we compared the renal hemodynamic effects of dapagliflozin with gliclazide in type 2 diabetes. The mGFR and effective renal plasma flow were assessed using inulin and para-aminohippurate clearances in the fasted state, during clamped euglycemia (5 mmol/L) and during clamped hyperglycemia (15 mmol/L). Filtration fraction and renal vascular resistance were calculated. Additionally, factors known to modulate renal hemodynamics were measured. In 44 people with type 2 diabetes on metformin monotherapy (Hemoglobin A1c 7.4%, mGFR 113 mL/min), dapagliflozin versus gliclazide reduced mGFR by 5, 10, and 12 mL/min in the consecutive phases while both agents similarly improved Hemoglobin A1c (-0.48% vs -0.65%). Dapagliflozin also reduced filtration fraction without increasing renal vascular resistance, and increased urinary adenosine and prostaglandin concentrations. Gliclazide did not consistently alter renal hemodynamic parameters. Thus, beyond glucose control, SGLT2i reduce mGFR and filtration fraction in type 2 diabetes. The fact that renal vascular resistance was not increased by dapagliflozin suggests that this is due to post-glomerular vasodilation rather than pre-glomerular vasoconstriction.

Association of KCNQ1 polymorphisms with gliclazide efficacy in Chinese type 2 diabetic patients.

To investigate the effects of KCNQ1 polymorphisms on the efficacy of gliclazide in type 2 diabetic patients. A total of 443 newly diagnosed type 2 diabetic patients were included in this study. After enrollment, patients went on an 8-week gliclazide monotherapy. Fasting plasma glucose (FPG) was measured before and after the treatment. Life-style information was collected by weekly follow-up. Genotyping of the two single-nucleotide polymorphisms was performed using the single base primer extension method. T-test, one-way analysis of variance, and Pearson χ-test were used to evaluate the effects of rs2237892 and rs2237897 on the FPG reduction and treatment success rate. After 8 weeks of gliclazide therapy, the FPG decreased significantly from 10.9±2.8 to 7.4±2.2 mmol/l (P<0.001). Compared with the CC genotype, patients with CT or TT genotypes of rs2237897 achieved greater reduction in FPG (3.9±2.6 vs. 3.2±2.4 mmol/l, P=0.003; 33.9±19.0 vs. 27.7±17.4%, P<0.001) and a higher rate of treatment success (74.1 vs. 65.2%, P=0.042 for criterion 1; 61.1 vs. 44.5%, P<0.001 for criterion 2, respectively), whereas no significant difference was found in the FPG reduction and treatment success rate among different genotypes of rs2237892. Our results indicated that a common variant of KCNQ1, rs2237897, was associated with the efficacy of gliclazide after 8-week monotherapy in Chinese newly diagnosed type 2 diabetic patients. The FPG reduction and treatment success rate were significantly higher in carriers of CT and TT genotypes.

CYP2C93 variant is associated with antidiabetes efficacy of gliclazide in Chinese type 2 diabetes patients.

Aims/IntroductionThe objective of the present study was to investigate the effects of CYP2C9*3 polymorphisms on the therapeutic response to gliclazide in type 2 diabetes patients.Materials and MethodsA total of 746 incident type 2 diabetes patients were included in this study. After enrolment, patients went on 4‐week gliclazide monotherapy. Fasting plasma glucose was measured before and after treatment. Hypoglycemia episodes and lifestyle information were collected by weekly follow up. Genotyping of rs1057910 was carried out using the single base primer extension method. The t‐test, analysis of variance and chisquare‐test were used to evaluate the effects of rs1057910 alleles on the therapeutic response to gliclazide.ResultsAfter the therapy, fasting plasma glucose decreased significantly from 11.2 ± 2.7 mmol/L to 8.0 ± 2.2 mmol/L (P < 0.001). Patients with AC/CC genotypes of rs1057910 had a greater reduction of fasting plasma glucose (3.6 vs 3.0 mmol/L, P < 0.001; 31.4 vs 24.5%, P < 0.001) and a higher rate of treatment success (54.7 vs 37.5%, P < 0.001; 51.4 vs 32.3%, P < 0.001; 71.6 vs 48.3%, P < 0.001 for criterion 1, 2 and 3, respectively).ConclusionsThe present study showed that the polymorphism at rs1057910 significantly affected the therapeutic response of gliclazide in type 2 diabetes mellitus patients. The risk allele is associated with a greater decrease of fasting blood glucose and a higher rate of treatment success with gliclazide monotherapy.

Comparison of daytime 12‐hour metabolic profiles after treatment with repaglinide and gliclazide in type 2 diabetes

AbstractThis study aimed to compare the effect of repaglinide and gliclazide on glucose and pancreatic beta‐cell secretory products in response to serial test meals, over a 12‐hour period during the day, in patients with type 2 diabetes (T2DM).T2DM subjects (n=12), on metformin and repaglinide three times a day preprandially, underwent baseline 12‐hour glucose and hormonal (specific insulin and intact proinsulin) daytime profiles in response to three identical standard 500kcal test meals 4?hours apart. Subjects were then switched from repaglinide to twice‐daily gliclazide for the study period of three months, after which the 12‐hour profiles were repeated under identical conditions.Fasting plasma glucose, insulin and intact proinsulin concentrations were similar with the two treatments. Postprandial glucose excursions were significantly lower with repaglinide for both Meals 1 and 2 (both p &lt; 0.05). Insulin to glucose ratios were significantly greater with repaglinide in response to Meal 1 (p &lt; 0.01). Postprandial insulin and intact proinsulin (all p &lt; 0.01) responses were also significantly higher with repaglinide after the first meal.Repaglinide is a more potent and shorter‐acting insulin secretagogue but its effects are predominantly in response to the first meal of the day, which may be influenced by the relatively higher beta‐cell secretory capacity after a period of fasting. Copyright © 2013 John Wiley &amp; Sons.

Glyburide is Associated with a Higher Risk of Acute Coronary Events Compared to Gliclazide: A Nested Case-control Study

The potential cardiotoxic effect of sulfonylureas is thought to occur by blocking cardiac KATP channels and therefore impeding ischemic preconditioning. At usual therapeutic doses glyburide is more likely to inhibit cardiac KATP channels than gliclazide. We examined the risk of acute coronary syndrome (ACS) associated with the use of glyburide compared to gliclazide in type 2 diabetes patients.

Antioxidant and vascular effects of gliclazide in type 2 diabetic rats fed high-at diet

Diabetes mellitus is characterized by oxidative stress, which in turn determines endothelial dysfunction. Gliclazide is a sulphonylurea antidiabetic drug with antioxidant effects due to its azabicyclo-octyl ring. It has been reported to potentially protect the vasculature through improvements in plasma lipid levels and platelet function. We hypothesized that gliclazide has a beneficial effect on endothelial function in Goto-Kakizaki rats (GK), an animal model of type 2 diabetes fed an atherogenic diet for 4 months. We evaluated the influence of gliclazide on both metabolic and oxidative status and NO-mediated vasodilation. GKAD rats showed increased oxidative stress and impaired endothelium-dependent vasodilation. GKAD rats treated with gliclazide showed increased sensitivity to NO-mediated vasodilation, a significant decrease in fasting glycemia and insulinemia, and a significant decrease in systemic oxidative stress. In conclusion, our results suggest that gliclazide treatment improves NO-mediated vasodilation in diabetic GK rats with dyslipidemia probably due to its antioxidant effects, although we cannot rule out substantial benefits due to a reduction in fasting blood glucose. The availability of a compound that simultaneously decreases hyperglycemia, hyperinsulinemia, and inhibits oxidative stress is a promising therapeutic candidate for the prevention of vascular complications of diabetes.

Ser1369Ala Variant in Sulfonylurea Receptor Gene ABCC8 Is Associated With Antidiabetic Efficacy of Gliclazide in Chinese Type 2 Diabetic Patients

OBJECTIVE—The purpose of this study was to investigate whether genetic variants could influence the antidiabetic efficacy of gliclazide in type 2 diabetic patients.RESEARCH DESIGN AND METHODS—A total of 1,268 type 2 diabetic patients whose diabetes was diagnosed within the past 5 years and who had no recent hypoglycemic treatment were enrolled from 23 hospitals in China. All of the patients were treated with gliclazide for 8 weeks. Fasting and oral glucose tolerance test 2-h plasma glucose, fasting insulin, and A1C were measured at baseline and after 8 weeks of treatment. We used two independent cohorts to test the associations of 25 single nuclear polymorphisms in 11 candidate genes with the antidiabetic efficacy of gliclazide. A general linear regression model was used to test the association with adjustment for important covariates.RESULTS—After 8 weeks of gliclazide therapy, mean fasting plasma glucose (FPG) was reduced from 11.1 mmol/l at baseline to 7.7 mmol/l. In cohort 1, we genotyped all 25 SNPs (n = 661) and found that Ser1369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P = 0.002). We further genotyped Ser1369Ala in cohort 2 (n = 607) and confirmed the association identified in cohort 1. In the pooled analysis, compared with subjects with the Ser/Ser genotype, subjects with the Ala/Ala genotype had a 7.7% greater decrease in FPG (P < 0.001), an 11.9% greater decrease in 2-h plasma glucose (P = 0.003), and a 3.5% greater decrease in A1C (P = 0.06) after 8 weeks of treatment with gliclazide.CONCLUSIONS—In two independent cohorts of Chinese type 2 diabetic patients, we found consistent evidence that the Ser1369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide.

Association of sulfonylurea receptor 1 genotype with therapeutic response to gliclazide in type 2 diabetes

To investigate the effects of sulfonylurea receptor 1 (SUR1) exon 33 (TCC → GCC, S1369A) polymorphism on responsiveness to gliclazide. About 115 patients with type 2 diabetes were treated with gliclazide for 8 weeks. SUR1 genotypes were tested by Taqman-PCR. After gliclazide treatment, there was association between T/G polymorphism and decrease of HbA1c. G carriers were more sensitive to gliclazide and the decrease of HbA1c was more significant than TT genotype (TT, 0.76% ± 1.70%; TG + GG, 1.60% ± 1.39%, P = 0.044). The polymorphism of SUR1S1369A was associated with the therapeutic efficacy of gliclazide.

Is it time to re-assess the role of gliclazide? Targeting insulin resistance in type 2 diabetes patients suboptimally controlled with insulin

Background: Adult patients with type 2 diabetes controlled with insulin frequently require the addition of insulin sensitising drugs such as metformin and sometimes glitazones to achieve optimum glycaemic control. Five...

Double‐blind, randomized, multicentre study of the efficacy and safety of gliclazide‐modified release in the treatment of Chinese type 2 diabetic patients

Gliclazide-modified release (gliclazide MR) is a new formulation of the sulfonylurea gliclazide designed for once-daily administration. The hydrophilic matrix of hypromellose-based polymer in the new formulation induces a progressive drug release, which parallels the 24-h glycaemic profile in type 2 diabetic patients. The aim of this study was to compare the efficacy and safety of gliclazide MR (once-daily administration) versus gliclazide (twice-daily administration) in Chinese type 2 diabetic patients. Sixty-three type 2 diabetic Chinese patients who had been on diet control alone or on treatment with metformin or on low dose of sulfonylurea were randomized to either gliclazide MR taken once daily or gliclazide taken twice daily. Dosage of metformin was maintained throughout the study, and the sulfonylurea was stopped. The dose of gliclazide MR was increased at 1-month intervals from 30 mg to 120 mg, while that of gliclazide from 80 mg to 320 mg until metabolic control was achieved [fasting plasma glucose (FPG) < or = 7.7 mmol/l] or the maximum dose reached. Efficacy was mainly evaluated by levels of haemoglobin A1c (HbA1c) and FPG. The mean baseline characteristics of the full analysis set 1 (FAS1) (HbA1c, n = 58) and the FAS2 (FPG, n = 61) were comparable in both groups. The levels of HbA1c decreased similarly in both groups over the treatment period: -1.6 +/- 1.6% (p < 0.001) on gliclazide MR (n = 31) and -1.6 +/- 1.4% (p < 0.001) on gliclazide (n = 27). Decrease in HbA1c was observed irrespective of pre-existing therapy for diabetes: -2.3 +/- 1.5% for patients on diet alone; -0.6 +/- 1.3% for patients switched from sulfonylurea to study drug and -1.4 +/- 0.8% for patients on metformin in combination with study drug. FPG decreased significantly from 177.5 +/- 63.5 to 136.7 +/- 42.2 (p < 0.001, n = 32) on gliclazide MR and not significant from 188.2 +/- 62.6 to 163.7 +/- 67.9 (p = 0.059, n = 29) on gliclazide. Both treatments were very well tolerated with no major hypoglycaemic episodes requiring external assistance; only three patients experienced mild hypoglycaemic episodes. Once-daily gliclazide MR showed a better trend in improving blood glucose control in comparison with gliclazide in type 2 diabetic Chinese patients irrespective of the pre-existing anti-diabetic treatment. The safety profiles of gliclazide MR and gliclazide were similar with a small number of patients having reported hypoglycaemic episodes. Once-daily dosing with gliclazide MR should improve patient compliance, an important factor in long-term glycaemic control.

Comparison of the postprandial glucose and insulin profiles with nateglinide and gliclazide in type 2 diabetic patients

Aim The aim of this study was to compare glucose, insulin and proinsulin profiles during nateglinide and gliclazide treatment over an extended postprandial period. Materials and methods This double-blind crossover trial was conducted in 23 type 2 diabetic patients (mean HbA1C 6.6%; range 6.0—7.4%) who received, for one week each, nateglinide 120 mg t.i.d., gliclazide 80 mg b.i.d. and placebo, with a one week wash out period between treatments. Results The 2-hour postprandial glucose concentration was markedly lower with nateglinide than with gliclazide (5.83 vs. 7.21 mmol/L; p&lt;0.05), as was the post-meal peak glucose elevation (8.63 vs. 9.72 mmol/L; p=0.085), which was associated with earlier, higher and shorter-lived insulin and proinsulin secretory responses. However, 0—7-hour AUCs during standardised meal test for glucose and insulin between the two drugs did not statistically differ. No symptomatic hypoglycaemic events occurred during the 7-hour test period. Conclusion Nateglinide was more effective than gliclazide in controlling postprandial hyperglycaemia and showed a faster effect on insulin and proinsulin secretion.

Increased fibrinolytic potential induced by gliclazide in type I and type II diabetic patients

Despite the fact that the relationship between impaired diabetic control and the development of vascular complications now seems less controversial than before, we are still in a situation where interventions or strategies aimed at decreasing the complications of late diabetes have high priorities. It is believed that accelerated vascular disease in the diabetic population is caused by repeated intimal injury of the arteries, and there is also evidence that the accelerated vascular disease states cannot be attributed only to the hyperglycemic state. One factor of importance for delayed tissue repair and arteriosclerotic disease in diabetic patients might be a disordered endothelial cell-dependent fibrinolytic system. Here, we review the evidence of the relationship between increased fibrin deposition and defective fibrinolysis in diabetic patients, and, furthermore, we discuss the possible beneficial effects of an enhancement of endogenous endothelial cell-related fibrinolysis by sulphonylurea drugs.