Heart failure hospitalizations similar with DPP-4 inhibitors and other drug options

The retrospective cohort study used data on almost 80,000 new saxagliptin users and almost 300,000 new sitagliptin users, gathered through the FDA's Mini-Sentinel program from 2006 to 2013.


The risk of hospitalization for heart failure was similar between patients who started dipeptidyl peptidase-4 (DPP-4) inhibitors or other diabetes drugs, a new study found.

The retrospective cohort study used data from the FDA's Mini-Sentinel program, which includes 18 insurance and health system partners, gathered from 2006 to 2013. Almost 80,000 new saxagliptin users and almost 300,000 new sitagliptin users were included, with 7 to 9 months of follow-up data. They were compared to patients starting pioglitazone, second-generation sulfonylureas, or long-acting insulins. Results were published by Annals of Internal Medicine on April 26.

The patients starting DPP-4 inhibitors were found to have similar risk for heart failure hospitalization as those starting the other drugs. After stratification of patients by disease risk score, the study found reduced risks for heart failure when DPP-4 inhibitors were compared individually to other drugs. Results were similar among subgroups of patients defined by the presence or absence of cardiovascular disease and disease risk score.

There are several possible reasons that this study did not find the association between heart failure and DPP-4 inhibitors identified in the SAVOR-TIMI trial (a randomized postmarketing trial that compared saxagliptin to placebo), study authors said. One is that the SAVOR-TIMI findings were due to chance. However, other explanations include that the patients in the current study were significantly healthier, that the current study compared DPP-4 inhibitors to drugs that might carry their own risks (instead of placebo), and that the follow-up in the current study was shorter (7 to 9 months vs. 2.1 years). The authors called for additional randomized trials with an outcome of hospitalization for heart failure.

An accompanying editorial noted the same limitations but also said that the results “allay concerns about a saxagliptin-associated risk for heart failure.” The study's results also show the benefits of building systems to share data, including “answering safety and effectiveness questions quickly and more definitely, linking clinical trial investigation with real-world experience, eliminating waste and redundancy in research data collection, and incorporating the voices of patients and other stakeholders,” the editorialist said.

Annals of Internal Medicine's Diabetes Collection is online.