EFFICACY OF METFORMIN IN TYPE-II DIABETES - RESULTS OF A DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RESPONSE TRIAL

PURPOSE: To study the efficacy and safety of various dosages of metfor min as compared with placebo in patients with type II diabetes mellitu s. PATIENTS AND METHODS: A 14-week, multicenter, double-blind, dose-re sponse study was conducted. After a 3-week, single-blind, placebo-cont rolled washout, 451 patients with fasting plasma glucose levels of at least 180 mg/dL were randomized to receive an Ii-week course of placeb o or metformin given at 500, 1000, 1500, 2000, or 2500 mg daily. RESUL TS: Metformin improved glucose variables as compared with placebo. The adjusted mean changes in fasting plasma glucose from baseline associa ted with each metformin group at week 7, 11, or at endpoint exceeded t hose associated with placebo by 19 to 84 mg/dL at dosages of 500 to 20 00 mg daily, respectively. The corresponding between-group differences in glycated hemoglobin (HbA(1c)) ranged from 0.6% to 2.0% at dosages of 500 to 2000 mg daily, respectively. All between-group differences w ere significant (P < 0.05) for both fasting plasma glucose and HbA(1c) at week 7, week 11, and endpoint, except for the difference between p lacebo and metformin 500 mg in fasting plasma glucose at endpoint (P = 0.054). Treatment-related adverse events occurred in 15% of patients in the placebo group and in 28% in the metformin group (P = 0.02); the se were primarily manifested as digestive disturbances, such as diarrh ea. CONCLUSIONS: Metformin lowered fasting plasma glucose and HbA(1c) generally in a dose-related manner. Benefits were observed with as lit tle as 500 mg of metformin; maximal benefits were observed at the uppe r limits of the recommended daily dosage. All dosages were well tolera ted. Metformin appears to be a useful therapeutic option for physician s who wish to titrate drug therapy to achieve target glucose concentra tions. (C) 1997 by Excerpta Medica, Inc.