Incretin-based drugs for the treatment of type 2 diabetes mellitus do not increase the risk of hospitalization for heart failure, according to the findings from a large, observational study. After previous reports of an association between this class of drug and the occurrence of adverse pancreatic events, concerns have also been raised about a potential increased risk of heart failure. Three randomized, placebo-controlled trials to examine this issue showed conflicting results.

In a retrospective study, investigators analysed multiple cohorts across three countries, for a total of almost 1.5 million patients with diabetes. Study cohorts were further defined according to the presence or absence of a history of heart failure. Subsequently, the researchers performed a nested case–control analysis in which cohort members hospitalized for heart failure were matched with event-free controls — up to 20 controls for each case were randomly selected according to sex, age, date of study entry, duration of treated diabetes, and duration of follow-up.

In both study cohorts, treatment with incretin-based drugs — which include dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 mimetics — did not increase the risk of heart failure compared with combinations of oral antidiabetic drugs. Similar results were observed regardless of the class of incretin-based drug, duration of treatment, and history of myocardial infarction.

Despite the lack of information regarding the type of heart failure and the absence of long-standing diabetes in most cohort patients (who might have had a lower risk of heart failure) the investigators believe that they “had the statistical power to robustly assess this important drug safety issue” and conclude that “incretin-based drugs were not associated with an increased risk of hospitalization for heart failure”.