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Effect of Pioglitazone Compared with Metformin on Glycemic Control and Indicators of Insulin Sensitivity in Recently Diagnosed Patients with Type 2 Diabetes

Lilly Research Laboratories (I.P., M.H., D.J., B.J.S., A.F., M.H.T.), Eli Lilly \|[amp ]\| Company, Indianapolis, Indiana 46201; Bajcsy-Zsilinszky Hospital (G.J.), Budapest H-1106, Hungary; Medical School (T.T.V.), University of Szeged, Szeged H-6725, Hungary; St. Imre Hospital (Z.K.), Budapest H-1115, Hungary; Pandy Kalman Hospital (A.G.), Gyula H-5700, Hungary; Medical Military Academy (S.S.), Saint Petersburg, Russia 191186; and Endocrinology Research Center (M.S.), Moscow, Russia 117036

Address all correspondence and requests for reprints to: Imre Pavo, M.D., Ph.D., Lilly Research Laboratories, Lilly Corporate Center, Drop Code 2130, Indianapolis, Indiana 46285. E-mail: pavo_imre{at}lilly.com.

Pioglitazone, a thiazolidinedione, improves glycemic control primarily by increasing peripheral insulin sensitivity in patients with type 2 diabetes, whereas metformin, a biguanide, exerts its effect primarily by decreasing hepatic glucose output. In the first head-to-head, double-blind clinical trial comparing these two oral antihyperglycemic medications (OAMs), we studied the effect of 32-wk monotherapy on glycemic control and insulin sensitivity in 205 patients with recently diagnosed type 2 diabetes who were naive to OAM therapy. Subjects were randomized to either 30 mg pioglitazone or 850 mg metformin daily with titrations upward to 45 mg (77% of pioglitazone patients) and 2550 mg (73% of metformin patients), as indicated, to achieve fasting plasma glucose levels of less than 7.0 mmol/liter (126 mg/dl). Pioglitazone was comparable to metformin in improving glycemic control as measured by hemoglobin A1C and fasting plasma glucose. At endpoint, pioglitazone was significantly more effective than metformin in improving indicators of insulin sensitivity, as determined by reduction of fasting serum insulin (P = 0.003) and by analysis of homeostasis model assessment for insulin sensitivity (HOMA-S; P = 0.002). Both OAM therapies were well tolerated. Therefore, pioglitazone and metformin are equally efficacious in regard to glycemic control, but they exert significantly different effects on insulin sensitivity due to differing mechanisms of action. The more pronounced improvement in indicators of insulin sensitivity by pioglitazone, as compared with metformin monotherapy in patients recently diagnosed with type 2 diabetes who are OAM-naive, may be of interest for further clinical evaluation.

A portion of these data were presented at the 38th Annual Meeting of the European Association for the Study of Diabetes, Budapest, Hungary, 2002 [Diabetologia 45(Suppl 2):250 (Abstract 779) and 251-2 (Abstract 783)].

Abbreviations: A1C, Hemoglobin A1C; ALT, alanine transaminase; ANCOVA, analysis of covariance; ApoB, apolipoprotein B; AST aspartate transaminase; BP, blood pressure; FPG, fasting plasma glucose; FSI, fasting serum insulin; HDL-C, high-density lipoprotein cholesterol; HOMA, homeostasis model assessment; HOMA-IR, HOMA of insulin resistance; HOMA-S, HOMA for insulin sensitivity; LDL-C, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); OAM, oral antihyperglycemic medications; TEAE, treatment-emergent adverse event; TG, triglyceride; TZD, thiazolidinedione.

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