Eight RCTs were included in the review with 3,643 participants. Four RCTs were dose-finding studies, 3 RCTs compared glimepiride with other sulfonylureas, and 1 RCT added glimepiride or placebo to insulin therapy.
Glimepiride was as effective as second generation sulfonylureas.
In the dose-finding studies, two studies were combined statistically and reported that median changes from baseline to end point in FPG after 1, 4, and 8 mg of glimepiride exceeded those after placebo (p < 0.001) by 43, 70 and 74 mg/dL respectively. In the third study FPG decreased by 28% from a baseline of 212 mg/dL in the glimepiride group compared with 6% from a baseline of 205% mg/dL in the placebo group (p < 0.001). In the fourth study, glimepiride reduced plasma glucose throughout the 24-hour observation period regardless whether it was given in one or two divided doses.
In the first two studies, median HbA1C values at baseline for the placebo, 1-, 4- and 8-mg dose groups were 7.8%, 7.8%, 7.7%, and 7.8% respectively, and at end point were 9.5%, 8.0%, 7.7% and 7.5% respectively. The data from combining these two studies shows a dose response up to 4 mg, and the 4-mg dose appears to be nearly maximally effective. In the third study, the median baseline HbA1C in the glimepiride and placebo groups were 9.1% and 8.9% respectively, and at end point were 6.7% in the glimepiride group and 7.9% in the placebo group. In the active-controlled studies, in the two studies comparing glimepiride with glyburide, there were no statistically significant differences between the glimepiride and glyburide groups as measured by FPG, PPG or HbA1C. In the third study comparing glimepiride and glipizide, mean FPG concentrations were lower in the glimepiride group (p < 0.05) than in the glipizide group at every point during the titration phase except at week 12 (p = 0.053). Otherwise there were no statistically significant differences found between the two groups.
In the one study of adjunct therapy with insulin, glimepiride significantly lowered the requirement for exogenous insulin in patients with type 2 diabetes whose sulfonylurea therapy had failed. The mean daily insulin dose was significantly lower in the group that also received glimepiride than in the insulin-alone group (49 versus 78 units, p < 0.001).
Two thirds of patients achieved tight control (i.e. HbA1C less than or equal to 7.2%).
The most common adverse events were dizziness and headache, but no single adverse event occurred in more than 2% of patients.
In the U.S. the incidence of deaths, discontinuations due to adverse events, and other serious adverse events in the glimepiride group (10.3%) was approximately half that in the placebo group (21.4%) which was primarily attributable to the 17.0% incidence of hyperglycemia-related signs and symptoms in the placebo group. In Europe the slightly higher incidence of deaths, discontinuations due to adverse events, and other serious adverse events in the glimepiride group was attributable to the longer duration of treatment (i.e. less than or equal to 2.8 years).