Effects on Lipid Profile of Dipeptidyl Peptidase 4 Inhibitors, Pioglitazone, Acarbose, and Sulfonylureas: Meta-analysis of Placebo-Controlled Trials
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.
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.
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.
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.
KeywordsAcarbose Dipeptidyl peptidase 4 inhibitor Lipid profile Pioglitazone Sulfonylureas Type 2 diabetes
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- 3.American Diabetes Association. Standards of Medical Care in Diabetes 2012. Available at: care.diabetesjournals.org/content/35/Supplement_1/S11.full.pdf+html. Accessed Jan 1 2012.
- 4.International Diabetes Federation. Guide for Guidelines. Available at: www.idf.org/webdata/docs/Guide-for-Guidelines.pdf. Accessed Jan 1 2012.
- 5.Societa Italiana de Diabetologia. Guidelines [in Italian]. Available at: www.siditalia.it/pubblicazioni/linee-guida.html. Accessed Jan 1 2012.
- 29.Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279–1289.PubMedCrossRefGoogle Scholar
- 30.Aronoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider RL. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebocontrolled dose-response study. Diabetes Care. 2000;23:1605–1611.PubMedCrossRefGoogle Scholar
- 31.Mattoo V, Eckland D, Widel M, et al. Metabolic effects of pioglitazone in combination with insulin in patients with type 2 diabetes mellitus whose disease is not adequately controlled with insulin therapy: results of a six-month, randomized, double-blind, prospective, multicenter, parallelgroup study. Clin Ther. 2005;27:554–567.PubMedCrossRefGoogle Scholar
- 39.Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24- week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006;28:1556–1568.PubMedCrossRefGoogle Scholar
- 42.Jadzinsky M, Pfutzner A, Paz-Pacheco E, Xu Z, Allen E, Chen R. Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab. 2009;11:611–622.PubMedCrossRefGoogle Scholar
- 52.AstraZeneca. SAVOR-TIMI 53 (Does Saxagliptin Reduce the Risk of Cardiovascular Events When Used Alone or Added to Other Diabetes Medications). Identifier: NCT01107886. Available at: clinicaltrials.gov/ct2/show/NCT01107886?term =type+2+diabetes+mellitus+and+cardiovascular+di sease&rank=37. Accessed Dec 27 2011.Google Scholar
- 53.Merck. TECOS (Sitagliptin Cardiovascular Outcome Study). Identifier: NCT 00790205. Available at: clinicaltrials.gov/ct2/show/NCT00790205. Accessed Dec 27 2011.Google Scholar
- 54.Takeda Global Research & Development Center, Inc. Cardiovascular Outcomes Study of Alogliptin in Subjects With Type 2 Diabetes and Acute Coronary Syndrome (EXAMINE). Identifier: NCT00968708. Available at: clinicaltrials.gov/ct2/show/NCT00968708. Accessed Dec 27 2011.Google Scholar
- 55.Boehringer Ingelheim Pharmaceuticals. CAROLINA: Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes. Identifier: NCT01243424. Available at: clinicaltrials.gov/ct2/show/ NCT01243424. Accessed Dec 27 2011.Google Scholar
- 56.Nicholls SJ, Tuzcu EM, Wolski K, et al. Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. J Am Coll Cardiol. 2011;57:153–159.PubMedCrossRefGoogle Scholar