STEP-HFpEF: GLP-1 agonists the next class of HFpEF therapies?


Take Home Messages
  • Heart failure with preserved ejection fraction (HFpEF) is a debilitating condition associated with troubling symptoms and physical limitations, especially in those with obesity. No therapies have been developed to address obesity-related HFpEF.
  • The STEP-HFpEF trial examined the effect of semaglutide treatment in patients diagnosed with HFpEF who had concomitant obesity.
  • The study found semaglutide treatment in patients with HFpEF and obesity led to greater reductions in both symptoms and physical limitations as well as weight loss compared to placebo.
  • Further large-scale studies are needed to evaluate the long-term effects of GLP-1 receptor agonists as well as their impact on hard clinical endpoints in this patient population.

Heart failure with preserved ejection (HFpEF) is a condition underlined by impaired left ventricular (LV) diastolic function in the presence of normal contractile function, occurring due to the complex interplay between cardiometabolic comorbidities, inflammatory changes, volume overload and increased stiffness resulting in abnormal LV remodelling (1). HFpEF patients who are obese have been shown to demonstrate worse clinical and haemodynamic features compared to patients without obesity (2). Therefore, this patient population may respond favourably to weight loss measures. Glucagon-like peptide 1 (GLP-1) receptor agonists are an established treatment for type 2 diabetes mellitus and obesity, and have been shown to achieve effective weight loss and reduce major adverse cardiovascular events in those with concomitant cardiovascular or renal disease (3). Although a high proportion of patients with HFpEF are also obese, there is a paucity of obesity-targeting therapies in this particular population.