Heart failure outcomes and glucagon-like peptide-1 receptor agonists: A systematic review of observational studies

Abstract

Aim/objective: Recently, the glucagon-like peptide-1 receptor agonists (GLP-1RA) class showed a significant reduction in heart failure (HF) hospitalization in several meta-analyses of cardiovascular outcome trials (CVOTs). The objective of this systematic review is to summarize the real-world evidence regarding HF outcomes of GLP-1RAs.

Methods: We searched the PubMed and EMBASE databases for observational studies that investigated HF outcomes of GLP-1RAs.

Results: Our search yielded 10 observational studies. Of those, 7 were cohort studies, and 3 were nested case-control studies. The risk of HF was the outcome in four cohort studies. One study that compared exenatide and exenatide combined with insulin to insulin showed a reduction in HF risk in the exenatide and exenatide plus insulin groups (HR 0.34, 95% CI 0.22-0.52, p-value <0.001 and HR 0.40, 95% CI 0.32-0.50, p-value <0.001, respectively). The other three cohort studies did not show a statistically significant result. In the three cohort studies that investigated HF hospitalization as an outcome, two showed a lower rate of HF hospitalization [48 (16.7%) vs. 76 (28%), p-value <0.05 and HR 0.51, 95% CI 0.34-0.77, p = 0.002] in the GLP-1RA groups. Conversely, the remaining study showed a reduction of 14% in HF hospitalization in the dipeptidyl peptidase-4 inhibitors (DPP-4i) group compared to the GLP-1RA group (HR 0.86, 95% CI 0.83-0.90). In contrast to the cohort studies, the three nested case-control studies showed similar results of no association of GLP-1RA use and HF hospitalization with OR 0.67 (95% CI 0.32-1.42), HR 0.95 (95% CI 0.83-1.10), and OR 0.84 (95% CI 0.48-1.47), respectively.

Conclusion: The real-world evidence regarding the reduction in HF risk and hospitalization in GLP-1RA users is conflicting. Further well-designed, large multicenter, observational studies are needed to show clearer evidence.

Keywords: Cardiovascular disease; Diabetes mellitus; Glucagon-like peptide-1 receptor agonist; Heart failure; Hospitalizations for heart failure; Observational study; Systematic review; Type 2 diabetes mellitus.