Long‐term effects of pioglitazone and metformin on insulin sensitivity in patients with Type 2 diabetes mellitus

Aim  Despite their comparable glycaemic effects in patients with Type 2 diabetes mellitus (T2DM), pioglitazone and metformin may have different effects on insulin sensitivity because they have different mechanisms of action. We studied the changes in insulin sensitivity, as assessed by the Quantitative Insulin Sensitivity Check Index (QUICKI), in patients with T2DM who used metformin or pioglitazone as monotherapy or in combination therapy with sulphonylurea. Methods  Data in this report are from two multicentre, randomized, double-blind, double-dummy studies conducted in Europe (monotherapy) or in Europe and Canada (combination therapy study). Patients were randomized to 52 weeks of treatment consisting of a 12-week forced titration period and a 40-week maintenance period. HbA1c, fasting plasma glucose (FPG) and fasting serum insulin (FSI) were quantified from a single blood sample at weeks 0, 8, 16, 24, 32, 42 and 52. Insulin sensitivity was assessed with QUICKI, which is calculated from FSI and fasting blood glucose (FBG) concentrations using the formula 1/(log10 FSI + log10 FBG). Time course effects of the treatments were compared by repeated measures analysis of covariance. Results  As monotherapy, pioglitazone and metformin increased QUICKI compared with baseline (baseline vs. end point [mean ± sem]; pioglitazone [0.303 ± 0.001 vs. 0.321 ± 0.001; P < 0.001] and metformin [0.304 ± 0.001 vs. 0.315 ± 0.001; P < 0.001]). Pioglitazone increased insulin sensitivity more than metformin from week 4 through week 52. There were significant increases in QUICKI from baseline in both combination therapy groups (baseline vs. end point; pioglitazone + sulphonylurea [0.305 ± 0.001 vs. 0.319 ± 0.001; P < 0.001] and metformin + sulphonylurea [0.306 ± 0.001 vs. 0.317 ± 0.001; P < 0.001]). Overall, pioglitazone + sulphonylurea significantly increased insulin sensitivity more than metformin + sulphonylurea. Conclusion  Pioglitazone differed from metformin in its effects on insulin sensitivity despite both drugs having comparable glycaemic effects.