Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes

• Published in: Diabetic medicine Vol. 21; no. 8; pp. 859 - 866
• Main Authors: Tan, M. H., Johns, D., Strand, J., Halse, J., Madsbad, S., Eriksson, J. W., Clausen, J., Konkoy, C. S., Herz, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.08.2004; Blackwell
• Subjects: Biological and medical sciences; Blood Glucose - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; glibenclamide; Glyburide - therapeutic use; Humans; hyperglycaemia; Hypoglycemic Agents - therapeutic use; insulin resistance; Insulin Resistance - physiology; Lipids - blood; Male; Medical sciences; Middle Aged; pioglitazone; Thiazolidinediones - therapeutic use; Type 2 diabetes; Endocrinopathy; Type 2 diabetes; Human; Pioglitazone; Lipids; Thiazolidinedione derivatives; Insulin; Hypoglycemic agent; Regulation(control); Sensitivity; Sulfonylureas; hyperglycaemia; Glibenclamide; insulin resistance; Diabetes Mellitus; Type 2/blood/drug therapy
• ISSN: 0742-3071; 1464-5491; 1464-5491
• DOI: 10.1111/j.1464-5491.2004.01258.x

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 pioglitazone 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 glibenclamide group had significantly lower HbA1c than the pioglitazone group after 12 weeks of therapy (7.8% vs. 8.3%, P = 0.015), but significantly higher HbA1c 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 triglycerides (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 sustained 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.