Long-Term Treatment of Type 2 Diabetic Patients with the New Oral Antidiabetic Agent Glimepiride (Amaryl®): A Double-Blind Comparison with Glibenclamide

Abstract

An international, prospective, double-blind trial compared the long-term therapeutic value of glimepiride with glibenclamide in patients with Type 2 diabetes mellitus. Patients stabilised on glibenclamide were randomised to 1 mg glimepiride (524 patients) or 2.5 mg glibenclamide (520 patients). The treatment groups were comparable at baseline with respect to age (60.2 years), body mass index (26.5 kg/m2), duration of diabetes (5.0 years) and fasting blood glucose levels (163 mg/dl [9.0 mmol/l]). Doses were increased stepwise, up to 8 mg for glimepiride (once-daily) and 20 mg for glibenclamide (> 10 mg as divided dose), until metabolic control (fasting blood glucose < or = 150 mg/dl [8.3 mmol/l]), or maximum dose was achieved. After one year of treatment, patients entered a long-term follow-up study. Primary endpoints for evaluation of metabolic control, mean glycated haemoglobin and mean fasting blood glucose, were 8.4% and 174 mg/dl (9.7 mmol/l) for glimepiride and 8.3% and 168 mg/dl (9.3 mmol/l) for glibenclamide. Differences between treatment groups were not considered clinically relevant (95% confidence intervals (-0.05, 0.19%) for glycated haemoglobin and (2, 11 mg/dl) [0.1, 0.6 mmol/l] for fasting blood glucose). Statistically significant lower fasting insulin and C-peptide values were observed in glimepiride patients compared with glibenclamide (differences: insulin, -0.92 microU/ml [p = 0.04]; C-peptide, -0.14 ng/ml [p = 0.03]). Both treatment groups showed an equivalent safety profile. Adverse events were consistent with the nature of the diabetic patient population studied. Fewer hypoglycaemic reactions occurred with glimepiride than with glibenclamide (105 versus 150 episodes). The long-term follow-up (457 patients) confirmed that glimepiride (1-8 mg) once daily provides equivalent metabolic control to a higher dosage (2.5-20.0 mg) of glibenclamide. Both treatments were well tolerated.

Change in patients’ body weight after 12 months of treatment with glimepiride or glibenclamide in Type 2 diabetes: a multicentre retrolective cohort study

“…Both treatments enabled effective glycaemic control, as measured by HbA 1c and FBG concentrations, in agreement with previous studies [19]. As expected, both also reduced serum total cholesterol and LDL cholesterol, with an increase in HDL cholesterol seen only in the glimepiride group.…”

“…The mechanism behind the weight loss associated with glimepiride has not been established. However, it is likely that the lower insulin secretion stimulated by glimepiride relative to other SUs is involved [6,7,19,20]. Acute post-challenge hyperinsulinaemia predicts weight gain [21], and an intervention study in normoglycaemic, morbidly obese adolescents showed that metformin treatment led to greater weight loss than placebo [22].…”

A Systematic Review and Meta-Analysis of Hypoglycemia and Cardiovascular Events

“…Estimated for agreement on relevance was 0.86 (95% CI 0.81-0.91). Of the 21 articles, 12 compared glyburide with an oral hypoglycemic agent and reported this as patients experiencing at least one episode of hypoglycemia (13,(15)(16)(17)20,21,23,(25)(26)(27)29,30); an additional 3 articles only reported total number of hypoglycemic episodes (14,18,19); 3 articles compared glyburide with insulin (22,27,31); and 3 studies only reported a change in weight (24,28,32).…”

“…Twelve of the 21 studies reported the use of an intent-to-treat analysis (13,(15)(16)(17)20,21,23,(25)(26)(27)29,30). Loss to follow-up was reported in 19 studies (2,14 -23,25-32).…”

“…Figure 2 shows a 52% greater risk of experiencing at least one episode of hypoglycemia for participants receiving glyburide compared with those receiving other secretagogues (RR Five studies compared glyburide with other secretagogues and reported their results as total number of hypoglycemic episodes (14,15,19,20,26) (Table 1). These studies were heterogeneous (I 2 76.8%).…”