Clinical use of dipeptidyl peptidase-4 and sodium-glucose cotransporter 2 inhibitors in combination therapy for type 2 diabetes mellitus

Objective. To review the efficacy, safety, and tolerability of combination treatment regimens including a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes mellitus (T2DM). Methods. Clinical trials of combination therapies including a DPP-4 and/or SGLT2 inhibitor were identified through a PubMed database search. To be included, studies had to have a primary end point of change from baseline to >= 24 weeks in glycated hemoglobin, include >= 1 other oral antidiabetic drug (OAD), and have randomized more than 200 patients. Results were limited to medications approved by the US Food and Drug Administration at the time of the search (March 2015). Results. A total of 1534 articles for the DPP-4 inhibitor class and 434 articles for the SGLT2 inhibitor class were retrieved from PubMed. Of these, 33 articles from the DPP-4 inhibitor class and 24 articles from the SGLT2 inhibitor class were included for review. In each study, the addition of a DPP-4 or SGLT2 inhibitor as a second or third agent resulted in improved glycemic control versus comparator arms. Reductions in weight or lack of weight gain were consistently observed, as were low rates of hypoglycemic events, particularly when the combination regimen also included metformin. Overall, the pattern of adverse events observed in combination treatment groups was consistent with the known effects of the individual agents. Conclusion. Combination treatment with a DPP-4 and/or SGLT2 inhibitor is an efficacious option for patients with T2DM starting pharmacological therapy, or for patients who have received treatment but require additional glycemic control. Study findings indicate that the underlying mechanisms of action of DPP-4 inhibitors and SGLT2 inhibitors complement a variety of OADs.