Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.
The short-term (2-12 weeks) antihyperglycaemic efficacy of metformin (M), glibenclamide (G), and their primary combination (MG) 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 (FBG) 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 (FBG < or = 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). FBG 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.
Twenty-two NIDDM patients completed an open randomized cross-over study comparing metformin and glibenclamide over 1 year. The drugs had an equivalent effect on glycaemic control, but, in contrast to glibenclamide, metformin reduced body weight. Neither drug affected triglycerides, total- and LDL-cholesterol or C-peptide. Metformin caused a slight elevation of HDL-cholesterol (P less than 0.05). No serious adverse effects were observed. The results show that oral hypoglycaemic agents are not associated with undesirable effects on lipids and lipoproteins.
Oral combination therapy with biguanides (metformin) and sulfonylureas is discussed. The rationale for the use of this combination is based on the different sites of action of the two kinds of drugs and the possibility for obtaining additive or potentiating effects and reduced side effects. The clinical usefulness of chlorpropamide and glyburide in combination with metformin has been demonstrated in some clinical trials. The combination may provide satisfactory glycemic control for several years, and possibly insulin therapy can be postponed or even avoided. No special safety problems are encountered with the use of the combination other than those attributed to the use of metformin or sulfonylurea alone, i.e., lactic acidosis and hypoglycemia, respectively. The lethality risks of these associated conditions are comparable. It is concluded that more data are needed to evaluate the full clinical potential and the mechanism of action of oral combination therapy.
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