Comparison of effect of pioglitazone with metformin or sulfonylurea (monotherapy and combination therapy) on postload glycemia and composite insulin sensitivity index during an oral glucose tolerance test in patients with type 2 diabetes.

OBJECTIVE Pioglitazone, metformin, and gliclazide lower HbA(1c) and fasting plasma glucose in patients with type 2 diabetes. We compared the effects of these three drugs, used as monotherapy and in combination, on postload glycemia and composite insulin sensitivity index (CISI) in these patients. RESEARCH DESIGN AND METHODS Postload glycemia and CISI were analyzed for 940 patients who had oral glucose tolerance tests (OGTTs) in four multicenter, randomized, double-blind, double-dummy, parallel group clinical trials (pioglitazone versus metformin, pioglitazone versus gliclazide, pioglitazone plus sulfonylurea versus metformin plus sulfonylurea, and pioglitazone plus metformin versus gliclazide plus metformin). Plasma glucose and insulin were determined during the 3-h OGTT performed at baseline and after 1 year of therapy. Incremental area under the curve for glucose was the surrogate for postload glycemia. CISI was calculated using the formula {10,000/ radical of [(fasting glucose x fasting insulin) x (mean glucose x mean insulin)]} during the OGTT. RESULTS In monotherapy, pioglitazone reduced postload glycemia and enhanced CISI more than metformin and gliclazide. In combination therapy, pioglitazone plus sulfonylurea reduced postload glycemia and increased CISI more than metformin plus sulfonylurea. Pioglitazone plus metformin also decreased postload glycemia and increased CISI more than gliclazide plus metformin. CONCLUSIONS Pioglitazone improves postload glycemia and CISI more than metformin or gliclazide when used as monotherapy or in combination therapy in patients with type 2 diabetes.