Efficacy and safety of GLP-1 agonists in obesity-related heart failure with preserved ejection fraction: a systematic review and meta-analysis of randomized placebo-controlled trials

Background Obesity increases the risk of heart failure with preserved ejection fraction. Glucagon-like peptide-1 (GLP-1) agonists are well-established weight-loss medications that showed positive outcomes in obese patients; however, their cardiovascular effects in patients with heart failure are still scarce. Aims This systematic review and meta-analysis of randomized control trials (RCTs) aims to assess the efficacy and safety of GLP-1 agonists in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Methods PubMed, Cochrane, and EMBASE were searched. The primary endpoint was the occurrence of a worsening heart failure event resulting in hospitalization, and a change in the clinical Summary Score (CSS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ). Secondary endpoints were all-cause mortality, cardiovascular death, C-reactive protein (CRP) reduction, change in 6-minute walk distance, reduction in body weight, change in waist circumference, and serious adverse events. A random-effect model was used to calculate mean difference (MD) and odds ratio (OR) with a 95% confidence interval (CI). Results A total of 3 RCTs met the inclusion criteria and were included in the qualitative and quantitative analysis comprising 1,876 patients. The GLP-1 group was associated with significantly fewer events of worsening heart failure event resulting in hospitalization versus placebo (OR= 0.37 [95% CI [0.10, 1.34]), (P = 0.0003). The mean difference of the KCCQ-CSS showed an increase in the GLP-1 group (MD= 7.33 [95% CI [5.96, 8.70]), (P < 0.00001). There were no statistically significant differences between patients taking GLP-1 or placebo regarding the occurrence of all-cause deaths (OR= 0.95 [95% CI 0.32, 2.84]), (P = 0.86), cardiovascular deaths (OR= 0.68 [95% CI 0.07, 6.84]), (P = 0.53) and serious adverse events (OR= 0.63 [95% CI 0.19, 2.02]), (P = 0.09). CRP levels were lower in the GLP-1 group compared to the placebo group (MD= -32.77 [95% CI [-41.48, -24.05]) (P < 0.00001). Distance in the 6-min walk was however increased among the GLP-1 group (MD= 16.83 [95% CI [9.11, 24.55]) (P < 0.00001). A reduction of ≥10% in body weight was significantly higher in the GLP-1 group (OR= 12.81 [95% CI 0.13, 1242.93]), (P < 0.00001). Additionally, the GLP-1 group showed a decrease in waist circumference with an MD=-7.64 [95% CI [-24.14, 8.86]), (P < 0.00001). Conclusions GLP-1 agonist treatment significantly improved heart failure-related outcomes in terms of reduced hospitalizations, enhanced KCCQ score, lower CRP levels and increased 6-minute walking distance.