Issue 120 Item 12 Single-Tablet Metformin-Glibenclamide Provides Type 2 Diabetic

New metformin-glibenclamide combination tablet may provide type 2 diabetics improved glycemic control than higher doses of either drug alone. >Dr. Michel Marre, Hospital of Xavier Bichat, in Paris, France, and colleagues evaluated the efficacy and tolerability of two dosage strengths of single-tablet metformin-glibenclamide combination, compared with each drug alone in patients with Type 2 diabetes and blood sugar levels inadequately controlled by metformin alone.

In the 16-week, double-blind, multicentre trial, 411 patients were randomized to receive either metformin 500 mg, glibenclamide 5 mg, or combination tablets consisting of 500 mg of metformin and 2.5 mg of glibenclamide, or combination tablets containing 500 mg of metformin plus 5 mg of glibenclamide.

All therapies were titrated with intention to achieve a fasting plasma glucose level no higher than 7 mmol/l.

Decreases in glycated hemoglobin (HbA1c) and fasting plasma glucose were significantly greater for both dosage tablets of metformin-glibenclamide, compared with either metformin or glibenclamide monotherapy, the researchers reported.

An HbA1c less than seven percent was achieved by 75 percent of patients on the higher-dose tablet and 64 percent on the lower-dose tablet, compared with only 42 percent for patients receiving glibenclamide monotherapy and 38 percent of patients receiving metformin monotherapy.

Target HBA1c levels were achievable using the lowest mean drug doses with either combination tablet, compared with either monotherapy. Using the low-dose tablet, the target HbA1c level was achieved with only 1225 mg of metformin plus 6.1 mg of glibenclamide.

With the high-dose tablet, the goal was reached using 1170 mg of metformin plus 11.7mg of glibenclamide. Patients on monotherapy required either 1660 mg of metformin or 13.4 mg of glibenclamide to achieve the same benefit.

Treatment-related serious adverse events occurred only in two patients who were receiving glibenclamide monotherapy. Overall, plasma lipid profiles were unaffected and mean changes in body weight were 1.0 kg.

"Intensive management of type 2 diabetes mellitus with a new metformin-glibenclamide combination tablet improved glycemic control and facilitated the attainment of glycemic targets at lower doses of metformin or glibenclamide, compared with the respective monotherapies, without compromising tolerability," the researchers concluded. Diabet Med 2002; 19: 673-680