Aims To evaluate the efficacy and safety of two dosage strengths of a single-tablet metformin–glibenclamide (glyburide) combination, compared with the respective monotherapies, in patients with Type 2 diabetes mellitus (DM) inadequately controlled by metformin monotherapy.
Methods In this 16-week, double-blind, multicentre, parallel-group trial, 411 patients were randomized to receive metformin 500 mg, glibenclamide 5 mg, metformin–glibenclamide 500 mg/2.5 mg or metformin–glibenclamide 500 mg/5 mg, titrated with the intention to achieve fasting plasma glucose (FPG) ≤ 7 mmol/l.
Results Decreases in glycated haemoglobin (HbA1c) and FPG were greater (P < 0.05) for metformin–glibenclamide 500 mg/2.5 mg (−1.20% and −2.62 mmol/l) and 500 mg/5 mg (−0.91% and −2.34 mmol/l), compared with metformin (−0.19% and −0.57 mmol/l) or glibenclamide (−0.33% and −0.73 mmol/l). HbA1c < 7% was achieved by 75% and 64% of patients receiving metformin–glibenclamide 500 mg/2.5 mg and 500 mg/5 mg, respectively, compared with 42% for glibenclamide and 38% for metformin (P = 0.001). These benefits were achieved at lower mean doses of metformin or glibenclamide with metformin–glibenclamide 500 mg/2.5 mg and 500 mg/5 mg (1225 mg/6.1 mg and 1170 mg/11.7 mg) than with glibenclamide (13.4 mg) or metformin (1660 mg). Treatment-related serious adverse events occurred in two patients receiving glibenclamide. Plasma lipid profiles were unaffected and mean changes in body weight were ≤ 1.0 kg.
Conclusions Intensive management of Type 2 DM with a new metformin–glibenclamide combination tablet improved glycaemic control and facilitated the attainment of glycaemic targets at lower doses of metformin or glibenclamide compared with the respective monotherapies, without compromising tolerability.
Diabet. Med. 19, 673–680 (2002)