A multicenter observational study of incretin-based drugs and heart failure

Background — Concerns have been raised that antidiabetic incretin-based drugs, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) analogs, can increase the risk of heart failure (HF). Ongoing clinical trials may not have the size to effectively address this issue.

Methods — We applied the same protocol in the analysis of multiple cohorts of patients with diabetes using healthcare data from six jurisdictions in Canada, the US, and the UK. Using a nested case-control analysis, each patient with HF was matched with up to 20 controls selected from its respective cohort on sex, age, cohort entry date, duration of treated diabetes, and follow-up. Cohort-specific hazard ratios (HRs) for HF with current use of incretin-based drugs, compared with the use of other oral antidiabetic drug combinations, were estimated by conditional logistic regression and pooled across cohorts using random-effects models.

Results — The cohorts included 1,499,650 patients, with 29,741 hospitalized for HF (incidence rate: 9.2 per 1,000 per year). The rate of HF was not increased with the use of incretin-based drugs compared with the use of other drug combinations among patients with (HR=0.86, 95% confidence interval (CI)=0.62-1.19) and without a history of HF (HR=0.82, 95% CI=0.67-1.00). The results were similar for DPP-4 inhibitors and GLP-1 analogs.

Conclusions — In this analysis of data from large cohorts of diabetic patients, incretin-based drugs were not associated with an increased risk of hospitalization for HF compared with commonly-used oral antidiabetic combinations. (Funded by the Canadian Institutes of Health Research DSE-111845; ClinicalTrials.gov number, NCT02456428).