Effects on Lipid Profile of Dipeptidyl Peptidase 4 Inhibitors, Pioglitazone, Acarbose, and Sulfonylureas: Meta-analysis of Placebo-controlled Trials

Introduction: Lipid profile is an important determinant of cardiovascular risk in type 2 diabetes. It is well known that patients with type 2 diabetes are more likely to be dyslipidemic than the general population. Given the observed connection between glucose and lipid metabolism in patients with type 2 diabetes, it is conceivable that different glucose-lowering agents can have a varying impact on the lipid profile. When metformin monotherapy fails, other drugs can be added to achieve sufficient glycemic control. Available oral agents include pioglitazone, acarbose, dipeptidyl peptidase 4 (DPP-4) inhibitors, and insulin secretagogs. The present meta-analysis was designed to assess the effect of DPP-4 inhibitors, pioglitazone, insulin secretagogs, and acarbose on blood lipids when compared to placebo.

Methods: An extensive search (any date up to November 1, 2011) was performed for all trials performed on the following classes of drugs: gliptin, insulin secretagogs, pioglitazone, and acarbose. The following endpoints were considered: endpoint total, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) and triglycerides.

Results: The difference in mean total cholesterol values at endpoint versus baseline was significantly higher in patients on pioglitazone, sulfonylureas, and DPP-4 inhibitor treatment (but not on acarbose) than those on placebo, demonstrating that treatment with these drugs (except acarbose) is associated with a significant reduction in total cholesterol. With respect to triglycerides, a significant reduction could be observed with acarbose, pioglitazone, and DPP-4 inhibitors, but not with sulfonylureas. HDL-C appeared to be increased by treatment with acarbose and pioglitazone, and decreased by sulfonylureas.

Conclusion: The present meta-analysis shows that available glucose-lowering drugs may have varying effects on the lipid profile. DPP-4 inhibitors, acarbose, and pioglitazone seem to have a more favorable effect on the lipid profile than sulfonylureas.