OBJECTIVE To review the clinical pharmacology data regarding the sulfonylurea glimepiride, and to summarize the clinical trials of glimepiride efficacy and safety alone and in combination with insulin for the treatment of type 2 diabetes mellitus. METHODS A MEDLINE database search (English language, January 1985-April 1997) was performed to identify relevant published articles, including reviews and abstracts; the manufacturer (Hoechst Marion Roussel, Kansas City, MO) provided unpublished data. METHODS Pharmacology information was taken from representative original research articles. Eight clinical studies were selected for analysis on the basis of large enrollment, appropriate study design, and publication of results. METHODS All clinical trials, published and unpublished, were reviewed. RESULTS Glimepiride is a sulfonylurea that is pharmacologically distinct from other sulfonylureas because of differences in receptor-binding properties and potentially selective effects on ATP-sensitive K+ channels. The pharmacokinetic and pharmacodynamic profile of glimepiride makes it suitable for once-daily dosing. The safety and efficacy of glimepiride have been confirmed in studies involving more than 5000 patients with type 2 diabetes. In one study, once-daily doses of 1-8 mg reduced fasting plasma glucose from baseline by 43-74 mg/dL more than did placebo (p < 0.001), and hemoglobin (Hb) A1C values decreased by 1.2-1.9% more than with placebo (p < 0.001). Two-thirds of patients achieved tight control (i.e., HbA1C < or = 7.2%). Glimepiride was as effective as second-generation sulfonylureas. The most common adverse events were dizziness and headache, but no single adverse event occurred in more than 2% of patients. CONCLUSIONS Glimepiride appears to be a useful option for patients with type 2 diabetes not controlled by diet and exercise and who want to achieve tight glucose control. Glimepiride can be used alone, in combination with other antihyperglycemic agents, or in patients with secondary sulfonylurea failure, as an adjunct to insulin therapy.