Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes

Bernd Richter, Elizabeth Bandeira-Echtler, Karla Bergerhoff, Christian Lerch

Cochrane Metabolic and Endocrine Disorders Group, Department of General Practice, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany

Background: In type 2 diabetes mellitus (T2DM) there is a progressive loss of β-cell function. One new approach yielding promising results is the use of the orally active dipeptidyl peptidase-4 (DPP-4) inhibitors. However, every new compound for T2DM has to prove long-term safety especially on cardiovascular outcomes.

Objectives: Systematic review and meta-analysis of the effects of sitagliptin and vildagliptin therapy on main efficacy parameters and safety.

Selection criteria, data collection, and analysis: Randomized controlled clinical studies of at least 12 weeks’ duration in T2DM.

Results: DPP-4 inhibitors versus placebo showed glycosylated hemoglobin A_1c (A1c) improvements of 0.7% versus placebo but not compared to monotherapy with other hypoglycemic agents (0.3% in favor of controls). The overall risk profile of DPP-4 inhibitors was low, however a 34% relative risk increase (95% confidence interval 10% to 64%, P = 0.004) was noted for all-cause infection associated with sitagliptin use. No data on immune function, health-related quality of life and diabetic complications could be extracted.

Conclusions: DPP-4 inhibitors have some theoretical advantages over existing therapies with oral antidiabetic compounds but should currently be restricted to individual patients. Long-term data on cardiovascular outcomes and safety are needed before widespread use of these new agents.

Keywords: DPP-4 inhibitors, sitagliptin, vildagliptin, systematic review, meta-analysis