Abstract

Combination therapy for type II (non-insulin-dependent) diabetes mellitus with insulin and sulfonylureas has been a topic of interest since the latter were introduced to clinical use. In recent years, improved understanding of potential complications associated with hyperinsulinemia has led to resurgent interest in alternatives to insulin monotherapy for patients who have failed on a regimen of diet and sulfonylureas. A plethora of clinical trials have reported on the efficacy of oral hypoglycemic agents in limiting insulin requirements while achieving glycemic control in this subset of diabetic patients. However, few studies have been appropriate in both design and duration to provide convincing results. The randomized placebo-controlled double-blind trials that have used a parallel design and study periods of up to 1 yr have uniformly investigated second-generation sulfonylureas and yielded the most reliable information. In all instances, the combination regimen achieved reduction in insulin requirement with varying evidence of a pancreatic effect as the responsible mechanism. This treatment modality is becoming more widely accepted in the effort to achieve optimal glycemic control with minimum risk to the patient.