Role of glucagon-like peptide-1 agonists in obesity and heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) currently represents the majority of all heart failure cases in the community. Glucagon-like peptide-1 agonists represent a class of medications used to treat type 2 diabetes mellitus and, in some cases, obesity. This class includes semaglutide. In the available data from the Semaglutide Treatment Effect in People with Obesity (STEP) trials that were done, looking at weight loss effects of semaglutide, there was a 30-40% reduction in C-reactive protein levels, and that suggests that there is a significant anti-inflammatory effect. Recently, the STEP-HFpEF trial enrolled 529 non-diabetic patients with HFpEF and obesity who were randomly assigned to once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. A statistically significant improvement in the quality of life score and in weight loss was observed. Statistically significant improvements were also seen in the 6 min walk distance, levels of C-reactive protein, and N-terminal pro-B-type natriuretic peptide levels. Interestingly, the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity trial has shown that semaglutide produced a consistent reduction of around 20% vs. placebo across major cardiovascular event endpoints over the ∼3-year follow-up in patients with overweight or obesity and cardiovascular disease but not diabetes.