To assess the efficacy of glimepiride in T2DM, Goldberg et al randomized 304 patients to receive either placebo or one of the three doses (1, 4, or 8 mg) of glimepiride during a 14-week study period.29
All glimepiride regimens significantly reduced FPG, PPG, and HbA1c
< 0.001) compared to placebo by the end of the study period. Median changes in FPG levels were 43, 70, and 74 mg/dL at glimepiride doses of 1, 4, and 8 mg, respectively. HbA1c
levels were lowered by 1.2%, 1.8%, and 1.9%, and the corresponding decreases in PPG were 63, 92, and 94 mg/dL, respectively. The 4- and 8-mg doses of glimepiride were more effective than the 1-mg dose; however, the 4-mg dose provided a nearly maximal antihyperglycemic effect.
Another study showed equal effects on FPG, PPG, HbA1c
, C-peptide, and insulin levels in a cross-over study of 98 patients treated with glimepiride.31
The only significant difference was observed in glucose levels throughout the day, which were lower with a once daily dose compared to a twice daily dosage. The opposite results were observed by Rosenstock et al31
who found a significant decrease in FPG by 0.6 mmol/L with glimepiride when it was given twice daily compared to once daily dosage.
Another multicenter, randomized, placebo-controlled clinical trial by Schade et al studied glimepiride (1–8 mg) titrated over 10 weeks compared with placebo in T2DM subjects who were not controlled by diet alone.32
In this study, glimepiride lowered FPG by 46 mg/dL, PPG by 72 mg/dL, and HbA1c
by 1.4% more than the placebo (P
< 0.001). Good glycemic control (HbA1c
< 7.2%) was achieved in 69% of glimepiride subjects compared to 32% of controls. C-peptide levels and non-fasting insulin levels were also increased in the study subjects.
Glimepiride monotherapy reduced both FPG and PPG levels more than placebo and once daily administration is equivalent to twice daily dosing. Studies also suggest that glimepiride controls blood glucose level throughout the day through its effect on stimulating insulin release, which appears to be greater 2 h after meals than under fasting conditions. These findings suggest that glimepiride enhances insulin and C-peptide secretion under physiologic conditions.
Combination therapy for treating T2DM is now a recommended practice as the disease progresses.10
Several studies have examined the combination of glimepiride with other oral hypoglycemic agents with different mechanisms of action for good glycemic control when monotherapy fails.33
In a study involving 372 patients with poorly controlled T2DM, glimepiride was added to metformin monotherapy. Study subjects were divided into three groups: metformin group, glimepiride group, metformin plus glimepiride group. In this study, a combination of glimepiride and metformin was shown to be more effective for controlling blood glucose levels compared to the use of either drug alone.33
Combination treatment was significantly more effective in controlling HbA1c (% change +0.07 ± 1.20 for metformin, +0.27 ± 1.10 for glimepiride, −0.74 ± 0.96 for combination treatment, P < 0.001). No significant difference was observed between metformin or glimepiride monotherapy with respect to change in HbA1c or fasting blood glucose; however, glimepiride was significantly more effective than metformin in reducing postprandial blood glucose. Episodes of symptomatic hypoglycemia was also higher in the combination group than in either monotherapy group (P = 0.039).