Effect of pioglitazone on lipids in well controlled patients with diabetes mellitus type 2 - Results of a pilot study

Introduction: Patients with diabetes mellitus type 2 are characterized by a typical dyslipoproteinemia. Improvement in glucose control usually also ameliorates this dyslipoproteinemia. It is unclear whether different antidiabetic strategies differ in their effects on the lipid profile. Particularly, it is unknown whether glitazones improve lipid values independently of their effects on glucose metabolism. Methods: Ten patients well controlled on sulfonylureas (HbA1c 6.9 +/- 0.5%) with diabetic dyslipoproteinemia were treated with additional pioglitazone (30 mg/d) for 3 months. Every 4 weeks the sulfonylurea dose was adjusted to keep HbA1c and fasting glucose constant. Before and after 3 months of pioglitazone therapy lipid metabolism was determined in detail (cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol, VLDL-triglycerides, lipoprotein(a), LDL-subtype distribution by isopycnic density gradient ultracentrifugation). Results: Although glucose control remained unchanged (HbA1c 6.9 +/- 0.5% vs. 6.8 +/- 0.6%: fasting glucose concentration 7.7 +/- 1.1 vs. 7.3 +/- 1.3 mmol/l) we observed a significant reduction in triglyceride concentration (1.9 +/- 0.6 vs. 1.4 +/- 0.5 mmol/l, -26%, p < 0.01), a significant increase in HDL-cholesterol concentration (1.2 +/- 0.2 vs. 1.4 +/- 0.2 mmol/l, +14%, p < 0.05), a significant decrease in LDL/HDL-ratio (3.03 +/- 0.77 vs. 2.51 +/- 0.61, -24%, p < 0.05) and non-significant improvements in total cholest LDL-cholesterol, VLDL-triglycerides, and VLDL-cholesterol concentrations. The LDL-subtype profile improved (significant reduction [-20%] in small dense LDL). Conclusions: This pilot study indicates that at comparable fasting glucose concentration and at comparable HbA1c value pioglitazone is superior to sulfonylureas concerning the improvement of diabetic dyslipoproteinemia. Whether this relates to indirect effects (improvement in insulin sensitivity) or direct effects (stimulation of PPARalpha) remains to be determined.