Authors: Jaime A. Davidson¹; André J. Scheen²; Harry C.S. Howlett³

Source: Drug Safety, Volume 27, Number 15, 2004 , pp. 1205-1216(12)

Publisher: Adis International

Abstract:

It is important to manage blood glucose intensively in patients with type 2 diabetes mellitus in order to reduce the risk of long-term complications. Oral combination therapy that addresses insulin resistance and -cell dysfunction is a proven means of improving glycaemic control when monotherapy becomes insufficiently effective. Metformin/glibenclamide (glyburide) combination tablets were developed to provide a means of applying this strategy while minimising polypharmacy. This review examines the tolerability profile of this treatment from four double-blind, randomised clinical trials in a total of 2342 type 2 diabetic patients with hyperglycaemia despite treatment with diet and exercise, a sulphonylurea or metformin. Treatment with combination tablets was associated with markedly superior blood glucose control, at lower doses of metformin and glibenclamide, compared with monotherapies. The incidence of symptoms of hypoglycaemia varied between dosages and trials, though the incidence of severe or biochemically confirmed hypoglycaemia or withdrawals from clinical trials for this reason was consistently low and comparable with glibenclamide alone. No patient required third-party assistance for hypoglycaemia. Significantly fewer diet-failed patients receiving low-dose combination tablets reported gastrointestinal adverse effects compared with metformin alone, with a comparable incidence between metformin and combination tablets in post-monotherapy studies. The incidence of other adverse events, including serious adverse events, was similar for combination tablets and monotherapies. The lower doses of metformin and glibenclamide with the combination tablet approach, and the design of the combination tablets themselves, may underlie the beneficial tolerability profile of this treatment.

Keywords: Glibenclamide/metformin, therapeutic use; Glibenclamide/metformin, adverse reactions; Adverse drug reactions; Benefit risk assessment; Type 2 diabetes mellitus

Document Type: Review article

Affiliations: 1: 1 University of Texas Southwestern Medical School, Dallas, Texas, USA 2: 2 Division of Diabetes, Division of Clinical Pharmacology and Therapeutics, Department of Medicine, Nutrition and Metabolic Disorders, CHU Sart Tilman, Liege, Belgium 3: 3 CardioMetabolic Care, Merck Santé, Lyon, France

Publication date: 2004-01-01

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