Amaryl scientific update |
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Vojnosanit Pregl. 2006 Dec;63(12):1015-20.
Jovanovic D, Stojsic D, Zlatkovic M, Jovic-Stosic J, Jovanovic M.
Military Medical Academy, National Poison Control Centre, Belgrade, Serbia.
Bioequivalence assessment of the two brands of glimepiride tablets.
BACKGROUND/AIM: Glimepiride, as an antidiabetic from the group of sulfonylurea, is administered perorally in the
treatment of diabetes mellitus. The aim of this study was to compare pharmacokinetic profiles and relative
bioavailabilities of the two oral formulations of glimepiride, generic and innovator tablets, after a single dose
of the active drug. METHODS: An oral dose of 6 mg glimepiride was given under fasting conditions to 24 healthy
volunteers. A one-week washout period was applied between the two consecutive periods. The serum samples obtained
before dosing, and at various time points up to 48 hours, were analyzed for glimepiride concentration using the
validated high-performance liquid chromatographic method with ultraviolet detection. Pharmacokinetic parameters
representing early (maximal concentration, time to reach maximal concentration) and total exposure (area under the
curve from the time 0 to the infinite time) to glimepiride were obtained and further analyzed using the
multifactorial analysis of variance and the non-parametric Wilcoxon signed ranks test. Comparison of the secondary
kinetic variables was only descriptive. RESULTS: The point estimates of the ratios of geometric means
(test/reference) of maximal concentrations and areas under the curve were 1.046 (90% confidence interval:
0.906-1.208) and 1.022 (90% confidence interval: 0.856-1.220), respectively, while the median values of times to
reach maximal concentration, at 5% level of significance, did not differ significantly. Both formulations were well
tolerated. Transient mild hypoglycaemia, which had been noted in 6 participants, resolved spontaneously within
30-60 minutes. CONCLUSION: Since all the parametric 90% confidence intervals for the log-transformed main variables
of glimepiride were within the 0.80 and 1.25 interval, accepted as the definition of bioequivalence, and the
differences in times to reach maximal concentration also did not reach statistical significance, studied tablets
were considered bioequivalent.
Diabetes Care. 2007 Apr;30(4):790-4.
Gottschalk M, Danne T, Vlajnic A, Cara JF.
University of California, San Diego Medical Center, San Diego, CA 92123, USA.
Glimepiride versus metformin as monotherapy in pediatric patients with type 2 diabetes: a randomized, single-blind comparative study.
OBJECTIVE: To compare the efficacy and safety of glimepiride versus metformin in pediatric subjects with type 2
diabetes inadequately controlled with diet and exercise alone or oral monotherapy. RESEARCH DESIGN AND METHODS:
This 26-week, single-blind, active-controlled, multinational study randomized 285 subjects to receive glimepiride
(1-8 mg once daily) or metformin (500-1000 mg twice daily) for 24 weeks. The primary end point was mean change in
A1C from baseline to week 24. Safety was assessed by incidence of hypoglycemia and other adverse events. RESULTS:
Significant reductions from baseline A1C were seen in both the glimepiride (-0.54%, P = 0.001) and metformin
(-0.71%, P = 0.0002) groups. A total of 42.4% (56 of 132) and 48.1% (63 of 131) of subjects in the glimepiride and
metformin groups, respectively, in the intent-to-treat population achieved A1C <7.0% at week 24. No significant
differences were observed between groups in reductions in A1C and self-monitored blood glucose levels, changes in
serum lipid concentrations, or hypoglycemia incidence. Significant differences were observed in mean changes from
baseline in BMI between groups (0.26 kg/m(2) for glimepiride and -0.33 kg/m(2) for metformin; P = 0.003). The
adjusted mean body weight increase was 1.97 kg for glimepiride and 0.55 kg for metformin (P = 0.005). A
hypoglycemic episode with blood glucose <50 mg/dl (<2.8 mmol/l) was experienced by 4.9 and 4.2% of glimepiride- and
metformin-treated subjects, respectively. A single severe hypoglycemic event occurred in each group. CONCLUSIONS:
Glimepiride reduced A1C similarly to metformin with greater weight gain, and there was comparable safety over 24
weeks in the treatment of pediatric subjects with type 2 diabetes.
Clin Lab. 2007;53(3-4):193-8.
Schondorf T, Forst T, Hohberg C, Lubben G, Armbruster FP, Roth W, Borchert M, Koder C, Lobig M, Grabellus M, Pfutzner A.
Institute of Clinical Research and Development, Mainz, Germany.
Relaxin expression correlates significantly with serum changes in VEGF in response to antidiabetic treatment in male patients with type 2 diabetes mellitus.
Recent studies indicate that relaxin as well as VEGF possess cardioprotective properties. This study aimed to
determine the association of relaxin with VEGF in patients with type 2 diabetes. We therefore analyzed samples from
a recent study showing the benefits of anti-diabetic treatment on cardiovascular risk markers independently from
glycemic control. VEGF, relaxin and markers of endothelial dysfunction, s-ICAM-1 and s-VCAM-1, were compared after
26 +/- 2 weeks of antidiabetic treatment with pioglitazone or glimepiride with their base line values. A total of
151 data sets (patients age, 62.7 +/- 8.1 years, diabetes duration, 6.8 +/- 6.6 years, 57 women, 94 men) were
available for the analysis. Baseline values were in median, relaxin: 27.4 pg/mL 125% quartile 15.8; 75% quartile:
45.21, s-ICAM-1: 294 ng/mL [25% quartile: 260; 75% quartile: 331], s-VCAM-1: 677 ng/mL [25% quartile: 589; 75%
quartile 871], VEGF: 350 pg/mL [25% quartile: 251; 75% quartile: 514]. Parameter variation after therapy showed a
significant correlation of relaxin expression with VEGF expression (p = 0.02) in the entire study group. The
correlation was seen in the subgroup of male patients (p < 0.01) but did not reach significance in the female
patients (p = 0.71). No further correlation was observed analyzing the other investigated parameters. Our data
suggest that relaxin may exert its cardioprotective action possibly via VEGF increase, particularly in men. In
women, other pathways may superimpose this effect. In conclusion, our study supports the hypothesis of different
regulating pathways and effects of relaxin in men and women also in patients with type 2 diabetes.
Diabetes Res Clin Pract. 2006 Sep 29;
Pan CY, Sinnassamy P, Chung KD, Kim KW; on behalf of the LEAD Study Investigators Group.
Department of Endocrinology, Chinese PLA Hospital, 28 Fuxing Road, Beijing 100853, China.
Insulin glargine versus NPH insulin therapy in Asian Type 2 diabetes patients.
OBJECTIVE: This study investigated the effect of insulin glargine (LANTUS((R))) versus NPH insulin on metabolic control and safety in Asian patients with Type 2 diabetes, inadequately controlled on oral hypoglycemic agents (OHAs). STUDY DESIGN AND METHODS: In this open-label, randomized, parallel, multinational, 24-week, non-inferiority study, 443 patients received either once-daily insulin glargine (n=220) or NPH insulin (n=223) at bedtime, plus glimepiride (Amaryl((R))). RESULTS: Baseline characteristics were similar between the two groups. HbA(1c) levels decreased in the insulin glargine and NPH groups over the study period in the per-protocol (PP; -1.10% versus 0.92%) and full-analysis (FA; -0.99% versus -0.77%) populations. In the PP population, the difference between adjusted means (predefined equivalence region >-0.4%) was 0.19% (90% confidence interval [CI]: 0.02, 0.36), demonstrating non-inferiority between the two treatments. In a superiority analysis (FA population), the difference between adjusted mean changes in the two groups was 0.22% (95% CI: 0.02, 0.42), demonstrating the superiority of insulin glargine (p=0.0319). Moreover, the number of hypoglycemic episodes was significantly lower with insulin glargine versus NPH insulin (p<0.004), particularly severe (p<0.03) and nocturnal (p<0.001). Daily insulin dose increased from 9.6+/-1.5 to 32.1+/-17.6U in the insulin glargine group and from 9.8+/-1.9 to 32.8+/-18.9U in the NPH insulin group. CONCLUSION: These results confirm earlier reports that insulin glargine provides superior glycemic control with less hypoglycemia and demonstrates that these benefits are consistent between different ethnicities.
Biochem Biophys Res Commun. 2005 Mar 11;328(2):484-90.
Inukai K, Watanabe M, Nakashima Y, Takata N, Isoyama A, Sawa T, Kurihara S, Awata T, Katayama S.
Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical School, Morohongo 38, Moroyama, Iruma-gun, Saitama 350-0495, Japan.
Glimepiride enhances intrinsic peroxisome proliferator-activated receptor-gamma activity in 3T3-L1 adipocytes.
Glimepiride, a third-generation sulfonylurea (SU), exerts its effects mainly by stimulating insulin secretion but has also been shown to have pleiotropic effects. Recent clinical studies showed glimepiride to enhance insulin sensitivity. In the present study, to clarify the mechanism by which insulin resistance is improved, we investigated the effects of glimepiride on AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma (PPARgamma) activity, using cultured adipocytes and muscle cells. When we treated fully differentiated 3T3-L1 adipocytes with 1muM glimepiride, endogenous PPARgamma transcriptional activity was significantly elevated, while AICAR-induced phosphorylation of AMPK was not affected in differentiated C2C12 myoblasts. The maximum PPARgamma activity enhancing effect of glimepiride is approximately 20% that of 1muM pioglitazone. In contrast, this mild PPARgamma-stimulatory effect was not observed under the same conditions with a 2nd generation SU, glibenclamide. Furthermore, with glimepiride treatment, transcriptional levels of aP2, the adipogenic marker gene, were increased 2.4- and 3.7-fold in 3T3-L1 adipocytes and fibroblasts, respectively. Analysis of triglyceride contents revealed glimepiride to promote differentiation of 3T3-L1 adipocytes. These results indicate that glimepiride has the potential to induce PPARgamma activity, thereby improving insulin resistance.
J Assoc Physicians India. 2004 Jun;52:459-63.
Ramachandran A, Snehalatha C, Salini J, Vijay V.
Diabetes Research Centre and M.V. Hospital for Diabetes WHO Collaborating Centre for Research, Education and Training in Diabetes Royapuram, Chennai.
Use of glimepiride and insulin sensitizers in the treatment of type 2 diabetes--a study in Indians.
AIM: Short-term efficacy of glimepiride, metformin and pioglitazone in newly diagnosed type 2 diabetes was compared with a group treated with diet and exercise. Effects on insulin secretion and sensitivity were also assessed. METHODS: New type 2 diabetic subjects, aged 30-60 years with BMI < 30 kg/m2 were selected. Subjects having glycosylated haemoglobin (HbA1c) of < 8.5% were advised diet and exercise (control group). Others having HbA1c > or = 8.5 to 11.0% were randomized to receive glimepiride (group 2), metformin (group 3) and pioglitazone (group 4). At the final review between 12-14 weeks, changes in plasma glucose, HbA1c, lipid profile, HOMA insulin resistance (HOMA-IR), beta cell function (HOMA-BF) and insulinogenic index (delta I/G) were measured. Comparisons were made using appropriate statistical analyses. RESULTS: Seventy-seven of the 97 subjects randomized equally into four groups, were available for review. Glycaemic parameters improved in all groups. Mean cholesterol decreased significantly in groups treated with metformin and pioglitazone. HDL-cholesterol increased with pioglitazone. Insulin resistance decreased significantly with metformin and pioglitazone, beta cell fuhction also showed improvement CONCLUSIONS: Glycaemic control was seen in all study groups, the improvement was better in drug treated groups than in the control group. Glimepiride improved insulin secretion including the early phase secretion and reduced plasma triglycerides. Metformin and pioglitazone had beneficial effects on lipid levels, improved insulin sensitivity and improved insulin secretion also.
J Diabetes Complications. 2004 Nov-Dec;18(6):367-76.
Davis SN.
Division of Diabetes Endocrinology and Metabolism, Vanderbilt University Medical School, 715 Preston Research Building, Nashville, TN 37232-6303, USA.
The role of glimepiride in the effective management of Type 2 diabetes.
Type 2 diabetes mellitus, a disorder of impaired insulin secretion and insulin resistance, has reached epidemic proportions. The effective management of Type 2 diabetes is of vital concern to clinicians. The identification of high-risk individuals and lifestyle management can help control diabetes; however, most patients require pharmacologic intervention. The goals of pharmacologic therapy are to achieve adequate glycemic control while avoiding hypoglycemia and weight gain and to minimize the risk of future micro- and macrovascular complications. There are a number of available glucose-lowering agents from which to choose. This review focuses on the sulfonylureas, the first oral agents introduced for the management of Type 2 diabetes, which are effective, well-tolerated, and well-established drugs, Second-generation sulfonylureas are now widely used in the management of Type 2 diabetes. The most recent addition, glimepiride, can be used in combination with metformin, the thiazolidinediones, alpha-glucosidase inhibitors, and insulin. The unique properties of glimepiride may provide advantages over other currently available insulin secretagogues.
Manag Care. 2004 Jul;13(7):48-9, 53-6, 58-9.
Kabadi UM.
Division of Endocrinology, University of Iowa Hospitals and Clinics, Iowa City 52246-2208, USA.
Cost-effective management of hyperglycemia in patients with type 2 diabetes using oral agents.
Diabetes exacts an enormous toll on health care resources, with extremely high costs attributable to care of diabetes patients in proportion to the afflicted population. Though individual treatment strategies are required for each patient, newer long-acting sulfonylureas may be the initial drugs of choice, as they may be the only oral agents that inhibit the processes inducing hyperglycemia--hepatic glucose production and glucose utilization by the tissues--by improving insulin secretion and insulin resistance. Sulfonylureas also represent the most cost-effective therapeutic option, alone or in combination with other oral agents or insulin. The newer long-acting agents, glimepiride and glipizide GITS, may be more attractive among sulfonylureas, due to their greater insulin-sparing property, fewer hypoglycemic events, weight neutrality, and once-daily dosing. Glimepiride may be preferred due to its safety profile, especially for the elderly and those with hepatic and/or renal dysfunction.
Diabetes Nutr Metab. 2004 Jun;17(3):143-50.
Derosa G, Franzetti I, Gadaleta G, Ciccarelli L, Fogari R.
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Metabolic variations with oral antidiabetic drugs in patients with Type 2 diabetes: comparison between glimepiride and metformin.
Patients with Type 2 diabetes (T2DM) are at high risk of morbidity and mortality from cardiovascular complications, and hypoglycaemia increases this risk. Furthermore, other metabolic parameters exacerbate cardiovascular risk in these patients. The aim of the study was to compare the metabolic effects of glimepiride and metformin in patients with T2DM. We evaluated 164 patients with T2DM (80 males, 84 females) in a multicentre, randomised, controlled, open, parallel group study comparing glimepiride with metformin. Eighty-one patients (aged 56+/-10 yr) received glimepiride (3+/-1 mg/d); 83 patients (aged 58+/-9 yr) received metformin (2500+/-500 mg/d). Patients had been diagnosed for < or = 6 months; they were non-smokers; had no hypertension or coronary heart disease; were not taking hypolipidaemic drugs, diuretics, beta-blockers or thyroxin; and had normal renal function. Metabolic parameters were measured after 6 and 12 months of treatment. Glimepiride significantly lowered lipoprotein(a) [Lp(a)] and homocysteine levels (HCT) at 6 and 12 months. Both glimepiride and metformin lowered plasminogen activator inhibitor Type 1 (PAI-1) at 12 months and significantly improved levels of glycosylated haemoglobin, fasting plasma glucose and post-prandial plasma glucose after 6 and 12 months. Metformin significantly lowered fasting plasma insulin and postprandial plasma insulin. Glimepiride and metformin also reduced levels of other metabolic parameters in patients with T2DM. In particular, glimepiride significantly reduced HCT, Lp(a), and PAI-1 levels, important metabolic risk factors for atherosclerotic vascular disease. These reductions may be owing to improved glucose metabolism, but it cannot be excluded that these drugs have a direct effect on additional metabolic parameters.
Clin Ther. 2004 May;26(5):744-54.
Derosa G, Cicero AF, Gaddi A, Ragonesi PD, Fogari E, Bertone G, Ciccarelli L, Piccinni MN.
Department of Internal Medicine and Therapeutics, University of Pavia, Piazzale C. Golgi 2, 27100 Pavia, Italy.
Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with glimepiride: a twelve-month, multicenter, double-blind, randomized, controlled, parallel-group trial.
BACKGROUND: Glimepiride is approved as monotherapy and in combination with metformin or with insulin, whereas the combination of glimepiride with other antihyperglycemic drugs is under investigation. OBJECTIVE: The aim of this study was to assess the differential effect on glucose and lipid variables and tolerability of the combination of glimepiride plus pioglitazone or rosiglitazone in patients with type 2 diabetes mellitus (DM) and metabolic syndrome. METHODS: This 12-month, multicenter, double-blind, randomized, controlled, parallel-group trial was conducted at 3 study sites in Italy. We assessed patients with type 2 DM (duration, > or =6 months) and with metabolic syndrome. All patients were required to have poor glycemic control with, or to have experienced > or =1 adverse effect (AE) with, diet and oral hypoglycemic agents such as sulfonylureas or metformin, both given up to the maximum tolerated dose. All patients received a fixed oral dose of glimepiride, 4 mg/d divided into 2 doses, self-administered for 12 months. Patients also were randomized to receive oral pioglitazone (15 mg once daily) (G + P group) or oral rosiglitazone (4 mg once daily) (G + R group), self-administered for 12 months. We assessed body mass index (BMI), glycemic control (glycosylated hemoglobin [HbA(1c)], fasting and postprandial plasma glucose and insulin levels [FPG, PPG, FPI, and PPI, respectively], and homeostasis model assessment index), lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]), and lipoprotein variables (apolipoprotein [apo] A-I and apo B) at baseline and at 3, 6, 9, and 12 months of treatment. Treatment tolerability was assessed at each study visit using a thorough interview of patients, and comparisons of clinical and laboratory values to baseline levels. RESULTS: A total of 91 patients were enrolled in the study; 87 patients completed it (G + P group: 24 women, 21 men; mean [SD] age, 53 [6] years; G + R group: 20 women, 22 men; mean [SD] age, 54 [5] years). Patients in the G + P and G + R groups experienced significant increases in mean BMI at 12 months compared with baseline (4.92% and 6.17%, respectively; both, P < 0.05). The combination of glimepiride with pioglitazone or rosiglitazone significantly improved glycemic control in the study patients. At 12 months, we observed a 1.3% improvement in mean values for plasma HbA(1c) concentration (P < 0.01) 19.3% in FPG (P < 0.01), 16.3% in PPG (P < 0.01), 42.4% in FPI ), and 23.3% in PPI (P <0.05); no significant differences were found between treatment groups. Although the G + P group experienced a significant improvement at 12 months in almost all variables of lipid metabolism from baseline (TC, - 11%; LDL-C, -12%; HDL-C, 15%; and apo B, - 10.6% [all, P , 0.05]), the G + R group experienced a significant increase in mostly the lipid risk factors for cardiovascular disease (TC, 14.9%; LDL-C, 16.5%; TG, 17.9%; and apo B, 10.3% [all, P , 0.05]). Overall, no statistically significant changes in plasma aminotransferase activities were observed. Of the 87 patients who completed the study, 6.7% (3/45) of patients in the G + P group and 11.9% (5/42) of patients in the G + R group had transient, mild to moderate AEs that did not cause withdrawal from the trial. CONCLUSION: In this study of patients with type 2 DM and metabolic syndrome who did not respond adequately to, or experienced AEs with, diet and either a sulfonylurea or metformin previously, the combination of glimepiride plus pioglitazone was associated with a significant improvement in lipid and lipoprotein variables, whereas the combination of glimepiride plus rosiglitazone appears to not have had any clinically significant effect on lipid metabolism.
Pharmacotherapy. 2004 May;24(5):606-20.
Korytkowski MT.
Center for Diabetes and Endocrinology, Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Sulfonylurea treatment of type 2 diabetes mellitus: focus on glimepiride.
Sulfonylureas, which have evolved through two generations since their introduction nearly 50 years ago, remain the most frequently prescribed oral agents for treatment of patients with type 2 diabetes mellitus. Glyburide, glipizide, and glimepiride, the newest sulfonylureas, are as effective at lowering plasma glucose concentrations as first-generation agents but are more potent, better tolerated, and associated with a lower risk of adverse effects. Differences in their binding affinity to the beta-cell sulfonylurea receptor have been described, with preservation of cardioprotective responses to ischemia with glimepiride. Clinical studies have shown glimepiride to be safe and effective in reducing fasting and postprandial glucose levels, as well as glycosylated hemoglobin concentrations, with dosages of 1-8 mg/day. In comparative trials, glimepiride was as effective in lowering glucose levels as glyburide and glipizide, but glimepiride was associated with a reduced likelihood of hypoglycemia and a smaller increase in fasting insulin and C-peptide levels than glyburide, and a more rapid lowering of fasting plasma glucose levels than glipizide. Glimepiride also improves first-phase insulin secretion, which plays an important role in reducing postprandial hyperglycemia. Insulin secretagogues, specifically glimepiride, merit consideration as first-line therapy for patients with type 2 diabetes.
Drugs Today (Barc). 1998 May;34(5):401-8.
Clark CM Jr, Helmy AW.
Regenstrief Institute for Health Care, Richard L. Roudebush Veterans Affairs Medical Center and the Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Clinical trials with glimepiride.
Data from 21 placebo-controlled, active-controlled or noncomparative studies involving more than 6500 patients, more than 4220 of whom were treated with glimepiride, are reviewed. Glimepiride has a rapid onset of action and is effective at a single daily dose. It is equally effective as the other second-generation sulfonylureas at doses of 1-8 mg/day, with doses above 4 mg/day reserved for patients with initial HbA(1c) above 8%. Glimepiride (at doses yielding the same blood-lowering effect as glyburide and glipizide), has a safety profile somewhat superior to that of glyburide, glipizide and gliclazide at a lower mg/day dose. Glimepiride also has been shown to be safe and effective in combination with insulin. Finally, glimepiride has two pharmacologic properties which have theoretical advantages over the other currently available sulfonylureas, but which have not as yet been shown to be clinically significant: it does not activate the cardiovascular K(ATP) channel and it achieves equivalent metabolic control at lower insulin secretion levels than the other sulfonylureas.
Drugs Today (Barc). 1998 May;34(5):391-400.
Nguyen C, Pan J, Charles MA.
Diabetes Research Program, University of California, Irvine, California 92697, USA.
Preclinical studies of glimepiride.
The treatment of NIDDM is advancing on a number of fronts, ranging from the understanding of the mechanisms of action of existing agents to the development of new drugs. Glimepiride, the most recently U.S. approved sulfonylurea, is evaluated for its pancreatic and extrapancreatic activities in addition to safety, when compared with glibenclamide in preclinical studies. Glimepiride uniquely binds to the 65 kDa protein K(ATP) channel in pancreatic islet beta-cell membranes and directly stimulates insulin secretion. Glimepiride has a lower binding affinity and causes less insulin release than glibenclamide in normal dogs and humans. However, in various animal models, glimepiride produces a more rapid and pronounced blood glucose-decreasing activity than glibenclamide. In vivo studies indicate that glimepiride also significantly reduces HbA1c, blood glucose and fasting insulin levels via extrapancreatic activities. These insulin mimetic effects are supported by demonstration of stimulated lipogenesis in 3T3 adipocytes and glycogenesis in rat diaphragm, by more efficient translocation of GLTU4 in fat and skeletal muscle tissues, and by activation of key metabolic enzymes. The insulin sensitivity effects of glimepiride have been demonstrated in vivo by increased glucose disposal rates in euglycemic clamp studies and in vitro by increased sensitivity and responsiveness of insulin-induced glucose uptake. Moreover, glimepiride might stimulate insulin-mediated glucose utilization in hepatocytes. With exercise-induced hypoglycemia, a suppression of endogenous insulin secretion was observed for glimepiride only. Data accumulated from in vitro and animal studies suggest that glimepiride has the least cardiotoxic potential. Its relative activities in multiple cardiovascular studies do not correlate with its potency to lower blood glucose levels. Similar cardiovascular effects have been seen in human studies. In contrast to the lack of an acute action, chronic application of glimepiride to cultured cardiomyocytes was found to produce an approximate doubling of the basal glucose uptake rates by an insulin-independent pathway most probably involving increased protein expression of both GLUT1 and GLUT4. Like glibenclamide, glimepiride possibly has antiatherogenic activity by inhibiting platelet aggregation via suppression of arachidonic acid metabolism. Our recent studies on rats and humans indicated that glimepiride has immunomodulatory activity and this action appears to be related to lowering autoimmune responses rather than metabolic action. These studies have been extended to include glimepiride involvement with prevention of diabetes in BB rats using an islet transplantation model. Finally, sulfonylureas, including glimepiride, may be useful for treating and preventing NIDDM.
Clin Ther. 2004 Jan;26(1):63-9.
Kabadi MU, Kabadi UM.
Medical Service, Veterans Affairs Medical Center, Phoenix, USA.
Effects of glimepiride on insulin secretion and sensitivity in patients with recently diagnosed type 2 diabetes mellitus.
The exact mechanism of the efficacy of glimepiride in the achievement of glycemic control has not yet been clearly defined. OBJECTIVE: This study was conducted to examine the influence of glimepiride on insulin secretion and sensitivity in patients with type 2 diabetes mellitus (DM) of recent onset. METHODS: This 24-week, open-label, controlled trial was conducted at the Division of Endocrinology and Metabolism, Veterans Affairs Medical Center (Phoenix, Arizona). Study participants were aged 32 to 75 years and had recent-onset (established by a short duration of symptoms 6 weeks to 6 months prior to the study) type 2 DM, or were age-matched healthy volunteers (control group). In the diabetic patients, glimepiride tablets were administered orally, initially at 2 mg once daily in the morning, with the dosage increased by 1 mg every 2 weeks until fasting plasma glucose (FPG) decreased to 6.7 mmol/L; the dosage was then maintained for the remainder of the 24-week study period. Oral glucose tolerance tests (OGTTs) were conducted in the control group and before treatment and at 24 weeks after the achievement and maintenance of glycemic control (glycosylated hemoglobin <7.0%) in the diabetic group. For OGTT, plasma insulin and glucose levels were determined after the subjects fasted overnight and then at every 15 minutes for 2 hours after glucose challenge. RESULTS: Fourteen diabetic men (mean [SEM] age, 50 [6] years; range, 32-75 years) and 10 male healthy controls (mean [SD] age, 48 [5] years; range, 30-68 years) were enrolled. In the DM group, FPG decreased significantly after treatment ( P<0.001); fasting plasma insulin was markedly elevated before treatment (P<0.001 vs controls) and decreased after treatment ( P<0.01) but did not normalize; first-phase insulin secretion was markedly inhibited before treatment ( P<0.001 vs controls) and normalized after treatment ( P<0.001) total insulin secretion significantly improved after treatment ( P<0.01) but did not normalize. Finally, the pretreatment insulin sensitivity index decreased significantly (P<0.01) after treatment and normalized in 6 of 14 patients (42.9%) with type 2 DM. CONCLUSIONS: In this study, glimepiride achieved desirable glycemic control in patients with recent-onset type 2 DM through improvement in insulin secretion and sensitivity.
Przegl Lek. 2003;60(6):409-12.
Jasik M.
Katedra i Klinika Gastroenterologii i Chorob, Przemiany Materii Akademii Medycznej, w Warszawie.
[Glimepiride in daily practice] [Article in Polish]
Application of the strategies and principles of oral diabetic therapy in type 2 diabetes should be individualized based on the degree of hyperglycemia, insulin deficiency and insulin resistance. This paper presents the evaluation of the new third-generation sulfonylurea compound, glimepiride in daily practice. Glimepiride appears to have several clinical advantages over conventional sulfonylureas: different binding kinetics, advisable cardiovascular effects and beneficial extrapancreatic activity. This may explain the observation that glimepiride provides more stable blood glucose control and lower risk of hypoglycemia over some second-generation sulfonylureas. Glimepiride is safe and well tolerated in patients with type 2 diabetes. Finally, glimepiride also has been shown to be safe and effective in combination with other oral agents or with insulin treatment.
Diabetes Res Clin Pract. 2003 Jul;61(1):13-9.
Weitgasser R, Lechleitner M, Luger A, Klingler A.
1st Department of Medicine, St. Johanns Spital - Salzburg General Hospital, Salzburg, Austria.
Effects of glimepiride on HbA(1c) and body weight in Type 2 diabetes: results of a 1.5-year follow-up study.
Sulphonylureas are effective and well tolerated in patients with Type 2 diabetes, but may be associated with weight gain, and lack of compliance due to multiple daily dosing. This open, uncontrolled surveillance study examined the efficacy and safety of glimepiride, a new sulphonylurea, administered once daily in patients with Type 2 diabetes. A total of 1,770 patients were enrolled in the study, and 284 patients were selected for follow-up. Patients received 0.5 to >4 mg glimepiride once daily for 1.5 years. HbA(1c) was reduced from 8.4% at baseline to 7.1% after 4 months and 6.9% after 1 and 1.5 years (median intra-individual change from baseline: -1.4, -1.5, and -1.7%, respectively; P<0.0001). Treatment with glimepiride also resulted in significant and stable weight loss relative to baseline, with the exception of patients with a body mass index of <25 kg/m(2). Mean body weight was reduced from 79.8 kg at baseline to 77.9 kg after 4 months, 77.2 kg after 1 year, and 76.9 kg after 1.5 years (mean intra-individual change from baseline: -1.9 kg, P<0.0001; -2.9 kg, P<0.05; -3.0 kg, P<0.005, respectively). Therefore, once daily glimepiride provides effective glycaemic control, and may have advantages over other sulphonylureas, because it exhibits weight neutralizing/reducing effects in patients with Type 2 diabetes.
Med Arh. 2003;57(2):125-7.
Becic F, Kapic E, Becic E.
Institut za farmakologiju, Klinicku Farmakologiju i toksikologiju, Medicinski fakultet Univerziteta u Sarajevu.
[Glimepiride--an oral antidiabetic agent] [Article in Croatian]
Glimepiride is the oral antidiabetic, second-generation sulfonylurea. It is structurally similar to glyburide. Glimepiride exhibited more potent glucose-lowering effects than glyburide and longer duration of hypoglycemic effect. Glimepiride is useful in the treatment of non-insulin-dependent (type II) diabetes mellitus. Glimepiride is indicated as an adjunct to diet and exercise for non-insulin dependent diabetes mellitus. Glimepiride reduces glucose levels blood by stimulating insulin release from functional pancreatic beta cells in response to glucose. Glimepiride in daily dose 1 to 8 mg is causing a dose-related decrease blood glucose levels and glycosylated hemoglobin fasting state and postprandially. If the maximum dose of glimepiride fails to lower blood glucose sufficiently, metformine or insuline may be added to glimepiride monotherapy. Glimepiride is very safe drug and adverse effects causing by glimepiride are very rare. The risk of hypoglycemia after use of glimepiride is very small, therefore is the therapy with glimepiride is more preferable than the therapy with glibenclamide.
Biochem Biophys Res Commun. 2005 Mar 11;328(2):484-90.
Inukai K, Watanabe M, Nakashima Y, Takata N, Isoyama A, Sawa T, Kurihara S, Awata T, Katayama S.
Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical School, Morohongo 38, Moroyama, Iruma-gun, Saitama 350-0495, Japan.
Glimepiride enhances intrinsic peroxisome proliferator-activated receptor-gamma activity in 3T3-L1 adipocytes.
Glimepiride, a third-generation sulfonylurea (SU), exerts its effects mainly by stimulating insulin secretion but has also been shown to have pleiotropic effects. Recent clinical studies showed glimepiride to enhance insulin sensitivity. In the present study, to clarify the mechanism by which insulin resistance is improved, we investigated the effects of glimepiride on AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma (PPARgamma) activity, using cultured adipocytes and muscle cells. When we treated fully differentiated 3T3-L1 adipocytes with 1muM glimepiride, endogenous PPARgamma transcriptional activity was significantly elevated, while AICAR-induced phosphorylation of AMPK was not affected in differentiated C2C12 myoblasts. The maximum PPARgamma activity enhancing effect of glimepiride is approximately 20% that of 1muM pioglitazone. In contrast, this mild PPARgamma-stimulatory effect was not observed under the same conditions with a 2nd generation SU, glibenclamide. Furthermore, with glimepiride treatment, transcriptional levels of aP2, the adipogenic marker gene, were increased 2.4- and 3.7-fold in 3T3-L1 adipocytes and fibroblasts, respectively. Analysis of triglyceride contents revealed glimepiride to promote differentiation of 3T3-L1 adipocytes. These results indicate that glimepiride has the potential to induce PPARgamma activity, thereby improving insulin resistance.
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Drug category:Antidiabetic agents
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