https://diabetes.acponline.org/archives/2015/11/13/3.htm

DPP-4 inhibitors associated with lower mortality and cardiac risk than sulfonylureas as add-on therapy, study finds

When added to metformin, DPP-4 inhibitors were associated with reduced risks for all-cause death and stroke but did not appear to alter the risks for myocardial infarction and hospitalization for heart failure relative to sulfonylureas.


Dipeptidyl peptidase-4 (DPP-4) inhibitors as add-on therapy to metformin were associated with better outcomes than sulfonylureas, according to a recent study.

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Researchers in Taiwan used a national health insurance database to compare clinical outcomes when DPP-4 inhibitors or sulfonylureas were added to metformin in patients with type 2 diabetes. Patients who were at least 20 years of age between 2009 and 2012 were included, and those taking metformin who hadn't previously taken another oral hypoglycemic agent were considered enrolled in the study cohort when they filled a DPP-4 inhibitor or sulfonylurea prescription. The index date was defined as the first day on which a DPP-4 inhibitor or sulfonylurea was used. Patients using other hypoglycemic agents for diabetes control between the first day of metformin prescription and the index date were excluded from the study. The study outcomes were all-cause mortality; major adverse cardiovascular events (MACEs), including myocardial infarction and ischemic stroke; heart failure hospitalization; and hypoglycemia. Patients were followed until death or until Dec. 31, 2013. Results were published online Oct. 13 by Annals of Internal Medicine.

Overall, 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined. Mean age was approximately 58 years, and mean follow-up was 2.8 years. DPP-4 inhibitors as an add-on to metformin appeared to be associated with lower risks for all-cause death (hazard ratio [HR], 0.63; 95% CI, 0.55 to 0.72), MACEs (HR, 0.68; 95% CI, 0.55 to 0.83), ischemic stroke (HR, 0.64; 95% CI, 0.51 to 0.81), and hypoglycemia (HR, 0.43; 95% CI, 0.33 to 0.56) versus sulfonylureas. No effect was seen, however, on risks for myocardial infarction and hospitalization for heart failure.

The authors noted that the study was limited by its observational cohort design, the lack of information on diabetes control, and its relatively short follow-up, especially considering that DPP-4 inhibitors are fairly new drugs. “With respect to the clinical outcome of MACEs, we found that DPP-4 inhibitors reduced the risks for all-cause death and stroke but did not alter the risks for myocardial infarction and hospitalization for heart failure relative to sulfonylureas,” the authors wrote. “This study adds to the clinical evidence for the evaluation of cardiovascular risk in patients with [type 2 diabetes mellitus] treated with sulfonylureas versus DPP-4 inhibitors after metformin.”

The author of an accompanying editorial pointed out the increasing difficulty for physicians of keeping up with newly available classes of diabetes drugs and determining which therapy is best for each patient. He noted that while the study was able to relieve some of the concern that DPP-4 inhibitors might increase cardiac events versus sulfonylureas, it also “raises questions it cannot answer,” such as the effect of add-on therapy on glucose control. “How the observed rates of adverse outcomes might be weighed in clinical decision making would depend on whether the addition of a sulfonylurea resulted in lower hemoglobin A1c levels than the addition of a DPP-4 inhibitor. Is this greater efficacy worth the risk?” he continued.

“Good diabetes care requires the clinician and patient to set defined, individualized goals. Only with such targets in mind can the clinician balance concerns of adequate glycemic control and possible adverse events,” the editorialist wrote. “For each patient, the clinician must not only set goals for glucose control but also weigh patient concerns—hypoglycemia, weight gain, affordability, or cardiac risk—that might modify these goals.”