Liraglutide in patients with heart failure with preserved ejection fraction and obesity without diabetes

Abstract Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed. Semaglutide and tirzepatide are emerging as promising therapies for heart failure with preserved ejection fraction (HFpEF) in patients with obesity, as demonstrated by recent clinical trials (STEP-HFpEF and SUMMIT), which showed reduced hospitalizations and improved quality of life. However, data on other GLP-1 RAs in HFpEF remain limited. Liraglutide is widly prescribed and shares a similar cost profile with other GLP-1 RAs and, together with semaglutide and tirzepatide, is approved by the FDA for management of obesity regardless of diabetes status. Therefore, we sought to evaluate the effect of liraglutide 3mg subcutaneously once daily in patients with HFpEF and obesity (BMI >30 kg/m^2), but without diabetes mellitus. Methods We conducted a retrospective cohort analysis of deidentified, aggregate patient data from the TriNetX research network. Patients aged ≥18 years with a history of HFpEF, a BMI >30 kg/m^2, and no history of diabetes mellitus, between January 2016 and January 2020 were identified. Patients were divided into two groups based on liraglutide use. Patients using other GLP-1 RAs were excluded. We conducted a 1:1 propensity score matching (PSM) for baseline demographics, BMI, prescribed medications, LVEF, and comorbidities, and, using odds ratios and Cox proportional hazards ratios, compared outcomes over a two-year follow-up period. The primary outcomes were all-cause death and acute HF exacerbations (defined by ICD codes or need for IV diuretics) and the secondary outcomes were ED visits for any cause, acute coronary syndromes (ACS), and stroke. Results The matched cohort included 458 patients with HFpEF (n = 229 per group; mean age: 62.8 years; 61.4% female; 75% White; mean HgbA1c: 5.69% ; mean LVEF: 61.4%; mean BMI: 37.5; 42% on SGLT2i and/or MRA ). Patients on liraglutide had a lower risk of all-cause mortality (OR: 0.342 [95% CI: 0.16-0.72]; P =0.004) and acute HF exacerbation (OR: 0.502 [95% CI: 0.35-0.73]; P < 0.001). ED visits (OR: 0.591 [95% CI: 0.51-0.93]; P = 0.012) were also less frequent in patients on liraglutide. ACS (OR: 0.477 [95% CI: 0.22-1.04]; P = 0.059) and stroke (OR: 1 [95% CI: 0.41-2.45]; P =1), were not significantly reduced in the liraglutide population. Time-to-event analysis of primary outcomes also demonstrated the benefits of GLP-1 RAs in this population (Figure 1). Conclusions The present analysis suggests that liraglutide use is associated with improved outcomes in patients with HFpEF and obesity (BMI >30) without diabetes mellitus, similar to those noted with other GLP1-RAs medications. Further studies are needed to confirm this association.Primary outcomes time to event analyses