ANTIHYPERGLYCEMIC EFFICACY, RESPONSE PREDICTION AND DOSE-RESPONSE RELATIONS OF TREATMENT WITH METFORMIN AND SULFONYLUREA, ALONE AND IN PRIMARY COMBINATION

The short-term (2-12 weeks) antihyperglycaemic efficacy of metformin (M), glibenclamide (G), and their primary combination (MC) was assessed in a double-blind study including 165 unselected patients with Type 2 diabetes. Patients with diet failure were randomized to M, G or MG. The dose was titrated with a fasting blood glucose concentration (FBC) of < 6.7 mmol l(-1) as the target, using at most six dose levels, the first three comprising increasing monotherapy (M or G) or low-dose primary combination (MGL), and the second three add-on therapies (M/G and G/M) and primary combination therapy escalated to high dose (MGH). Success rates were higher on MGL than on monotherapy. The difference in achieving acceptable control (FBC less than or equal to 7.8 mmol 1(-1)) was 70 % versus 51 % (95 % confidence interval 3-36 %, p = 0.032). When the drugs were combined, a slightly greater FBG reduction (p = 0.026) was observed, at lower dosage (p = 0.013). The response could not be predicted from body weight, but depended upon initial FBG (p = 0.019) and meal-stimulated C-peptide (p = 0.007). FBC declined progressively with increasing doses of metformin, whereas glibenclamide exerted most of its effect at low dose. Primary combination therapy with metformin and sulphonylurea may be clinically useful.