© 2004 Diabetes UK. Diabetic Medicine, 21, 859–866 859 DOI: 10.1111/j.1464-5491.2004.01258.x Introduction Insulin resistance and relative insulin deficiency are core defects in Type 2 diabetes mellitus. Insulin resistance affects skeletal muscle (by decreasing glucose uptake and utilization), adipose tissue (by decreasing suppression of intracellular lipolysis), and liver (by decreasing suppression of endogenous glucose production). Current pharmacotherapy of Type 2 diabetes includes sulphonylureas and glinides, which increase insulin secretion; α-glucosidase inhibitors, which retard digestion of complex carbohydrates; metformin, which reduces endogenous hepatic glucose production; and thiazolidinediones (TZDs), M.H. present address: F. Hoffmann-La Roche Ltd, Basel, Switzerland. Correspondence to: Meng H. Tan MD, Eli Lilly and Co., Lilly Corporate Center, Indianapolis, IN 46285, USA. E-mail: tan_meng@lilly.com Abstract Aims This study compared the effects of 52 weeks’ treatment with pioglitazone, a thiazolidinedione that reduces insulin resistance, and glibenclamide, on insulin sensitivity, glycaemic control, and lipids in patients with Type 2 diabetes. Methods Patients with Type 2 diabetes were randomized to receive either pioglitazone (initially 30 mg QD, n = 91) or micronized glibenclamide (initially 1.75 mg QD, n = 109) as monotherapy. Doses were titrated (to 45 mg for pio- glitazone and 10.5 mg for glibenclamide) to achieve glycaemic targets during the next 12 weeks: fasting blood glucose of ≤ 7 mmol / l and 1-h postprandial blood glucose of ≤ 10 mmol / l. Patients were maintained on the titrated dose for 40 weeks. Results Pioglitazone significantly increased insulin sensitivity compared with glibenclamide, as assessed by homeostasis model assessment (17.0% vs. -13.0%; P < 0.001), quantitative insulin sensitivity check index (0.011 vs. - 0.007; P < 0.001) and fasting serum insulin (- 1.3 pmol / l vs. 23.8 pmol / l; P = 0.007). The gliben- clamide group had significantly lower HbA 1c than the pioglitazone group after 12 weeks of therapy (7.8% vs. 8.3%, P = 0.015), but significantly higher HbA 1c after 52 weeks of therapy (7.8% vs. 7.2%, P = 0.001). Pioglitazone significantly (vs. glibenclamide) increased mean HDL-C (P < 0.001), decreased mean trigly- cerides (P = 0.019), and decreased mean atherogenic index of plasma (AIP; P = 0.001) and mean total cholesterol / HDL-C (P = 0.004), without significantly elevating mean total cholesterol or mean LDL-C compared with glibenclamide. Conclusions These data suggest that the effects of pioglitazone are more sus- tained than those of glibenclamide for improving insulin sensitivity in patients with Type 2 diabetes, and that 52 weeks’ treatment with pioglitazone has favourable effects on glycaemic control and lipoprotein profile. Diabet. Med. 21, 859 – 866 (2004) Keywords pioglitazone, glibenclamide, Type 2 diabetes, hyperglycaemia, insulin resistance Blackwell Publishing, Ltd. Oxford, UK DME Diabetic Medicine 0742-3071 Blackwell Publishing, 2004 21 Original Article Original article Effects of pioglitazone and glibenclamide in patients with Type 2 diabetes M. H. Tan et al. Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes M. H. Tan, D. Johns, J. Strand*, J. Halse†, S. Madsbad‡, J. W. Eriksson§, J. Clausen, C. S. Konkoy and M. Herz for the GLAC Study Group Lilly Research Laboratories, Eli Lilly and Co., Lilly Corporate Center, Indianapolis, IN, USA, *Oulun Diakonissalaitos, Oulu, Finland, †Betanien Medical Laboratory, Diabetesklinikken, Oslo, Norway, ‡Hvidovre Hospital, Hvidovre, Denmark, and §Umeå University Hospital, Umeå, Sweden Accepted 22 October 2003