Fewer adverse effects with add-on DPP-4 inhibitors in diabetes

By Will Boggs MD

NEW YORK (Reuters Health) - As add-on therapy to metformin in type 2 diabetes, dipeptidyl peptidase-4 (DPP4) inhibitors are associated with fewer adverse outcomes than sulfonylureas, researchers from Taiwan report.

"Dipeptidyl peptidase-4 inhibitors reduced the risks of all-cause mortality and stroke, but did not alter the risks of myocardial infarction and hospitalization for heart failure relative to sulfonylureas as add-ons to metformin," Dr. Yung-Tai Chen from Taipei City Hospital in Taiwan told Reuters Health by email.

"Recently, the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus -Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) study raised concerns about the risks of heart failure in patients with type 2 diabetes mellitus receiving DPP-4 inhibitors," Dr. Chen said. "However, our study showed dipeptidyl peptidase-4 inhibitors had comparable risks of hospitalization for heart failure to sulfonylureas as add-ons to metformin."

Dr. Chen and colleagues used data from Taiwan's National Health Insurance Research Database to compare all-cause mortality and the occurrence of major adverse cardiovascular events (MACEs), including ischemic stroke and myocardial infarction (MI), hospitalization for heart failure, and hypoglycemia among 10,131 DPP4 inhibitor users and 60,209 sulfonylurea users.

During the 3.3 years average follow-up, there were fewer deaths of any cause in the DPP4 inhibitor group (5.6%) than in the sulfonylurea group (7.3%), which translated into a 37% lower risk for all-cause death in the DPP4 inhibitor group.

Compared with sulfonylurea users, DPP4 inhibitor users also had a 36% lower risk for ischemic stroke and a 57% lower risk of hypoglycemia, according to the October 13 Annals of Internal Medicine online report.

The risks of myocardial infarction and heart failure hospitalization did not differ significantly between the groups.

Results were similar in a propensity score matched analysis of 10,089 pairs of DPP4 inhibitor and sulfonylurea users.

"Because of diabetic disease progression, many patients fail to achieve target glycemic control after the initiation of metformin therapy," Dr. Chen said. "In addition to the results of randomized controlled trials, our population study provided the large-scale data about cardiovascular safety of dipeptidyl peptidase-4 inhibitors versus sulfonylureas as add-ons to metformin in the real world."

Dr. Chen added, "Because patients with type 2 diabetes mellitus belong to a heterogeneous subpopulation, treatment regimens of oral hypoglycemic agents should still be individualized based on the effects of blood glucose control and cardiovascular safety."

Dr. William B. White of the University of Connecticut School of Medicine in Farmington, a cardiologist who recently coauthored a paper on the safety of new drugs for type 2 diabetes, told Reuters Health by email, "DPP-4 inhibitors remain a safe class of therapies for type 2 diabetes based on both observational data (this paper) and the major cardiovascular outcome trials published between 2013 and 2015."

"The key reason to consider using a DPP-4 inhibitor over a sulfonylurea is the hypoglycemia benefit and the fact that no sulfonylurea has been studied as extensively as the incretin-based therapies," Dr. White said.

As for the specific outcomes in this trial, Dr. White said, "The reductions in mortality are extremely high and despite the controls, propensity matching, etc., they are fairly hard to believe, considering the results of SAVOR, EXAMINE, TECOS and ELIXA. The definitive trial CAROLINA (linagliptin versus sulfonylureas) will be out in two years or so and should define the benefits (or lack thereof) of DPP4 inhibition compared to sulfonylureas on cardiovascular outcomes."

SOURCE: http://bit.ly/1PrgqvH

Ann Intern Med 2015.

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