Incretin-based drugs not associated with greater heart failure hospitalization risk than other drug combos in retrospective study

Antidiabetic incretin-based drugs, including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) analogues, do not appear to be associated with greater heart failure hospitalization risk compared with commonly used combinations of oral antidiabetic drugs, according to a recent study.

Researchers used data from Canada, the U.S., and the U.K. to perform a retrospective nested case-control analysis of patients with diabetes, matching each patient hospitalized due to heart failure with a maximum of 20 controls, based on sex, age, date of entry to the cohort, duration of treated diabetes, and follow-up time. The authors used conditional logistic regression to calculate cohort-specific hazard ratios for heart failure hospitalization in patients taking incretin-based drugs and in those taking other combinations of antidiabetic drugs. Five mutually exclusive categories were used to classify current exposure to antidiabetic drugs among case-patients and controls: incretin-based drugs, insulin, 2 or more oral antidiabetic drugs used in combination, 1 oral antidiabetic drug, or no antidiabetic drug exposure. Current exposure was defined as “any prescription whose duration plus a 30-day grace period included the index date.” Random-effects models were used to pool hazard ratios across cohorts. Combined use of oral antidiabetic drugs was used as the primary reference group, given that incretin-based drugs are considered second- or third-line therapy, and thus used at a similar point in the management of the disease, the authors wrote. The study results were published in the March 24 New England Journal of Medicine.

Overall, 1,499,650 patients were included in the cohorts, 1,419,850 of whom had no history of heart failure. A total of 29,471 patients were hospitalized for heart failure over 3,242,291 person-years of follow-up, for a crude incidence rate of 9.2 events per 1,000 persons per year. History of heart failure was present in 79,800 patients (of these, 6,536 were hospitalized for heart failure) and absent in 1,419,850 patients (of these, 23,205 were hospitalized for heart failure). In patients with a history of heart failure, no increase was noted in rate of heart failure hospitalization with incretin-based drugs versus oral antidiabetic drug combinations (hazard ratio, 0.86; 95% CI, 0.62 to 1.19). The same was true in patients who had no heart failure history (hazard ratio, 0.82; 95% CI, 0.67 to 1.00). Hazard ratios were 0.84 (95% CI, 0.69 to 1.02) for DPP-4 inhibitors and 0.95 (95% CI, 0.83 to 1.10) for GLP-1 analogues when these drugs were considered separately.

The authors noted that their study's reference group included some patients taking thiazolidinediones, which are known to increase risk for heart failure hospitalization, and many patients who were taking sulfonylureas, which could increase risk of cardiovascular effects. In addition, they wrote, outcome status in some patients may have been misclassified, no data on ejection fraction were available, and most patients did not have long-term diabetes and thus may have had lower levels of cardiac risk. However, based on their analysis, they concluded that incretin-based drugs were not associated with increased risk for heart failure hospitalization. This finding was consistent in patients with and without heart failure history and for both DPP-4 inhibitors and GLP-1 analogues separately, they wrote.

See our coverage in this issue of a recently released FDA warning on certain DPP-4 inhibitors.