Disease relevance of glimepiride

• The pharmacokinetics, efficacy and safety of glimepiride were investigated in a single- and a multiple-dose open study in patients with non-insulin-dependent diabetes mellitus and renal impairment and an initial creatinine clearance above 10 ml/ min [1].
• AIMS/HYPOTHESIS: Our study compared the effects of glimepiride or glibenclamide treatment on body weight over 12 months of treatment in patients with Type 2 diabetes in routine outpatient practice [2].
• Mean weight loss and reduction in body mass index from baseline to study endpoint were greater with glimepiride than with glibenclamide (-2.04+/-3.99 kg vs -0.58+/-3.65 kg, p<0.001; -0.71+/-1.38 kg/m(2) vs -0.20+/-1.28 kg/m(2), p<0.001) [2].
• Concomitant use of fluconazole with glimepiride may increase the risk of hypoglycemia as much as would a 2- to 3-fold increase in the dose of glimepiride [3].
• Using human hepatoma Hep-G2 cells, we found that glimepiride did not affect insulin binding, insulin receptor isoform expression, and insulin-induced receptor internalization [4].

Psychiatry related information on glimepiride

• CONCLUSIONS: Patient compliance and treatment satisfaction with once-daily glimepiride were significantly better than with glibenclamide 2 to 3 times daily [5].

High impact information on glimepiride

• Inhibition of glucose transport or incubation of rat adipocytes in glucose-free medium completely abolished stimulation of GPI-PL by either insulin or glimepiride [6].
• Incubation of the cells with either insulin (0.1-30 nM) or the sulfonylurea, glimepiride (0.5-20 microM), in the presence of glucose led to conversion of up to 35 and 20%, respectively, of the total amphiphilic LPL and Gce1 to their hydrophilic versions [6].
• Furthermore, in 3T3-L1 adipocytes, glimepiride stimulated the transcriptional activity of the gene promoter containing PPAR-responsive element and altered mRNA levels of PPARgamma target genes including aP2, leptin, and adiponectin [7].
• Sulfonylurea (SU) agents, including glimepiride and glibenclamide, are the most widely used oral hypoglycemic drugs, which stimulate insulin secretion primarily by binding to the SU receptor on the plasma membrane of pancreatic beta-cells [7].
• Our observation that glimepiride and glibenclamide could act not only on SU receptor but also on PPARgamma may give an important clue to the development of novel antidiabetic drugs, which can enhance both insulin secretion from pancreatic beta-cells and peripheral insulin sensitivity [7].

Chemical compound and disease context of glimepiride

• Nondiabetic patients treated with glimepiride significantly lowered the ischemic burden assessed by an ST-segment shift, chest pain score, and myocardial lactate extraction ratios compared with the glibenclamide-treated patients, implying that acute administration of glimepiride did not abolish cardioprotection [8].
• Since hyperinsulinism and permanent K(ATP) closure are supposed to negatively affect the pathogenesis and therapy of non-insulin-dependent diabetes mellitus, the demonstrated higher insulin-independent blood glucose-lowering activity of Amaryl may be therapeutically relevant [9].
• OBJECTIVE: The goal of this study was to evaluate the efficacy and safety of glimepiride, a long-acting sulfonylurea, as an adjunct to diet/exercise in Mexican Americans with type 2 diabetes mellitus [10].
• Objective We examined the individual pharmacological effects of the addition of rosiglitazone and metformin to glimepiride on inflammatory markers and adipokines in patients with type 2 diabetes mellitus [11].
• BACKGROUND: Pioglitazone and glimepiride improve glycemic control in patients with type 2 diabetes mellitus by different mechanisms [12].

Biological context of glimepiride

• Short-term treatment of desensitized adipocytes with glimepiride or insulin reduced GLUT4 phosphorylation by approximately 70 and 25%, respectively, in both fractions [13].
• Pharmacokinetics and safety of glimepiride at clinically effective doses in diabetic patients with renal impairment [1].
• The increased plasma elimination of glimepiride with decreasing kidney function is explainable on the basis of altered protein binding with an increase in unbound drug [1].
• CONCLUSIONS: Glimepiride remarkably improved insulin resistance, suggested by a significant reduction in HOMA-IR, an increase in MCR-g, and a reduction in HbA(1c) without changing extrapancreatic beta-cell function and urine CPR [14].
• Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes [15].

Anatomical context of glimepiride

• Thus tolbutamide and gliclazide block channels containing SUR1 (beta-cell type), but not SUR2 (cardiac, smooth muscle types), whereas glibenclamide, glimepiride, repaglinide, and meglitinide block both types of channels [16].
• Effect of glimepiride on insulin-stimulated glycogen synthesis in cultured human skeletal muscle cells: a comparison to glibenclamide [17].
• Preincubation of the myotubes with wortmannin (100 nmol/l), an inhibitor of phosphatidylinositol (PI)- 3 kinase, caused an inhibition of this glimepiride effect on insulin-stimulated glycogen synthesis [17].
• Since insulin also stimulates membrane release of these GPI-modified proteins, and in combination with glimepiride in a synergistic manner, sulphonylurea drugs may exert their peripheral actions in adipose tissue by using (part of) the insulin postreceptor signalling cascade at the step of activation of a GPI-specific phospholipase C [18].
• In the present study, we tested the hypothesis that glimepiride may stimulate NO production in vascular endothelial cells [19].

Associations of glimepiride with other chemical compounds

• RESEARCH DESIGN AND METHODS: A total of 17 subjects with type 2 diabetes, inadequately controlled on a maximized oral antihyperglycemic double regimen of glimepiride and metformin, were randomized to the addition of rosiglitazone or insulin to their treatment regimens for a period of 6 months [20].
• The mean elimination half-life of glimepiride was prolonged from 2.0 to 3.3 hours (P <.0001) by fluconazole [3].
• Fluvoxamine moderately increased the plasma concentrations and slightly prolonged the elimination half-life of glimepiride [3].
• Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride [21].
• Cholesterol depletion blocks redistribution of lipid raft components and insulin-mimetic signaling by glimepiride and phosphoinositolglycans in rat adipocytes [22].

Gene context of glimepiride

• Plasma adiponectin plays an important role in improving insulin resistance with glimepiride in elderly type 2 diabetic subjects [14].
• When we treated fully differentiated 3T3-L1 adipocytes with 1 microM glimepiride, endogenous PPAR gamma transcriptional activity was significantly elevated, while AICAR-induced phosphorylation of AMPK was not affected in differentiated C2C12 myoblasts [23].
• Glibenclamide and glimepiride, on the other hand, block channels containing SUR1 and SUR2 with similar affinity [24].
• Increased plasma adiponectin and decreased plasma TNF-alpha may underlie the improvement of insulin resistance with glimepiride [14].
• OBJECTIVES: Our objective was to investigate the effects of genetic polymorphisms of cytochrome P450 (CYP) 2C9 on the pharmacokinetics of glyburide (INN, glibenclamide) and glimepiride, two widely used sulfonylurea antidiabetic drugs [15].

Analytical, diagnostic and therapeutic context of glimepiride

• This procedure was repeated with concomitant intraarterial infusion of:1) the sulphonylurea derivative glibenclamide (0.33 or 3.3 micrograms. min-1. dl-1, both n = 12), 2) the new sulphonylurea derivative glimepiride (2.5 micrograms.min-1. dl-1, n = 12) or 3) placebo (n = 12) [25].
• Change in patients' body weight after 12 months of treatment with glimepiride or glibenclamide in Type 2 diabetes: a multicentre retrospective cohort study [2].
• CONCLUSION: These results show that glimepiride maintains myocardial preconditioning, while glibenclamide might be able to prevent it [26].
• A similar reduction also occurred in the glimepiride group, in which repetitive balloon occlusion led to a 34% reduction (dilatation 2: 0.35; dilatation 3: 0.23 mV; CI -0.21 to -0.02 mV; P=0.01) [26].
• Myocardial ischemia after coronary angioplasty was evaluated in 20 nondiabetic and 23 diabetic patients chronically taking either glibenclamide or glimepiride [8].

References