Treatment strategies for secondary sulfonylurea failure. Should we start insulin or add metformin? Is there a place for intermittent insulin therapy?

UNLABELLED: Which therapy should be used in non-insulin dependent diabetes mellitus (NIDDM) with secondary sulfonylurea failure? Should we start insulin therapy, try a period of intensified insulin therapy and then switch back to sulfonylurea or should we add metformin therapy? To address this question, we have compared these three treatment strategies in 36 NIDDM patients who failed on treatment with sulfonylureas during a 6 month period. Insulin (short and intermediate-acting insulin before breakfast and dinner) and the combination of 21 mg of glibenclamide and 1.5 g of metformin resulted in an equivalent 30% improvement in glycemic control without significant effects on lipids. Intensified insulin therapy (6 weeks of intermediate and short-acting insulin 3 times daily), on the other hand, initially lowered blood glucose to the same degree as during the other two treatment regimes, but after switching back to sulfonylurea therapy (21 mg of glibenclamide/day) blood glucose concentrations returned to pretreatment values. Insulin therapy resulted in a 5 kg increase in body weight, 63% of which was accounted for by an increase in fat mass. Although body weight was unchanged during glibenclamide/sulfonylurea therapy, lean body mass and energy expenditure decreased significantly (p less than 0.05). Body weight and energy metabolism remained unchanged during intermittent insulin therapy.
CONCLUSIONS: Despite similar blood glucose lowering properties, insulin and the combination of sulfonylurea and metformin have different effects on energy metabolism and body composition. Since these effects were not observed during treatment with sulfonylurea alone, they must be ascribed to metformin.

RCT Entities:   Population Interventions Outcomes