A meta-analysis of randomized controlled trials comparing dipeptidyl peptidase-4 (DPP-4) inhibitors to metformin and other drugs found that DPP-4 monotherapy is less effective than metformin monotherapy for reducing hemoglobin A1c (HbA1c) levels, and that DPP-4 inhibitors plus metformin are less effective than metformin plus a sulfonylurea or a GLP-1 agonist.
Karagiannis and colleagues evaluated the safety and efficacy of DPP-4 inhibitors by assessing HbA1c levels, changes in body weight, and adverse events, most notably hypoglycemia.
The findings support the validity of guidelines that relegate use of DPP-4 inhibitors to patients at high risk for hypoglycemia or who are intolerant to other medications. The safety results were diluted by inconsistent definitions of hypoglycemia in the included trials. There was significant heterogeneity in the results, and only 3 trials had a low risk for bias for the primary outcome. Generalizability of the pooled outcomes therefore remains inconclusive.
Karagiannis and colleagues did not evaluate such hard clinical endpoints as cardiovascular events. Previous meta-analyses have not identified increased risks for cardiovascular outcomes with use of DPP-4 inhibitors, and a large-scale trial is under way to assess the effect of DPP-4 inhibitors on cardiovascular events.