STEP HFpEF DM: Semaglutide 2.4 mg Improves Functional Status, Symptoms in Patients with Diabetes, HFpEF

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The STEP HFpEF DM trial at ACC.24 shows significant improvements in symptoms among patients with obesity-related HFpEF and diabetes mellitus.

New data presented at the American College of Cardiology 2024 (ACC.24) Annual Scientific Sessions underlines the benefits of semaglutide in patients with heart failure with preserved ejection fraction (HFpEF), specifically those with concomitant diabetes mellitus and obesity.1

Presented by Mikhail Kosiborod, MD, results of the STEP HFpEF DM trial reaffirm the beneficial effects of semaglutide 2.4 mg (Wegovy) on quality of life and physical symptoms associated with HFpEF seen in the original STEP HFpEF trial.1,2

“Obesity forms a ‘common soil’ that can lead to the development of heart failure with preserved ejection fraction and type 2 diabetes, and patients living with both conditions suffer from an especially high symptom burden but have few available treatment options,” said Dr. Mikhail Kosiborod, lead study investigator and cardiologist at Saint Luke’s Mid America Heart Institute, Kansas City, USA.3

Presented at ESC Congress 2023, the original STEP HFpEF trial was a randomized, double-blind, placebo-controlled trial conducted at 96 sites in Asia, Europe, and North and South America. Comparing the effects of semaglutide 2.4 mg against placebo therapy on symptoms and functional status in adults with obesity and HFpEF, the trial 529 participants, with 266 and 263 randomized to the semaglutide 2.4 mg and placebo arms. The overall study cohort had a median age of 69 years, a median body weight of 105.1 kg, and a median BMI of 37 kg/m2, with 66% having a BMI of 35 kg/m2 or greater.2

The original trial was designed with dual primary endpoints defined as change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and change in body weight. The primary outcome analysis revealed the mean change in the KCCQ-CSS was 16.6 points with semaglutide 2.4 mg and 8.7 points with placebo (estimated treatment difference [ETD], 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; < .001). When assessing body weight reductions, results suggested the mean percentage change in body weight was −13.3% with semaglutide 2.4 mg and −2.6% with placebo (ETD, −10.7 percentage points; 95% CI, −11.9 to −9.4; < .001).2

In STEP HFpEF DM, investigators randomized 616 participants in a 1:1 ratio to semaglutide 2.4 mg or placebo therapy for 52 weeks. To be included, patients were required to have HFpEF, a BMI of 30 kg/m2 or greater, and type 2 diabetes. Overall, 310 patients were randomized to semaglutide and 306 were randomized to placebo.1

Like the original STEP HFpEF trial, STEP HFpEF DM had dual primary endpoints, which were change from baseline in the KCCQ-CSS and the change in body weight. STEP HFpEF DM also included multiple secondary confirmatory endpoints, these included change in 6-minute walk distance, a hierarchical composite end point of death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance, and the change in the C-reactive protein (CRP) level.1

Upon analysis, the mean change from baseline KCCQ-CSS was 13.7 points with semaglutide 2.4 mg and 6.4 points with placebo (ETD, 7.3 points; 95% CI, 4.1 to 10.4; P < .001). Assessments of body weight change indicated the mean change from baseline in body weight was −9.8% with semaglutide and −3.4% with placebo therapy (ETD, −6.4 percentage points; 95% CI, −7.6 to −5.2; P < .001). Results of the secondary endpoint analyses favored semaglutide 2.4 mg for change in 6-minute walk distance (estimated between-group difference, 14.3 meters; 95% CI, 3.7 to 24.9; P=.008), the hierarchical composite endpoint (win ratio, 1.58; 95% CI, 1.29 to 1.94; P < .001), and change in CRP level (estimated treatment ratio, 0.67; 95% CI, 0.55 to 0.80; P < .001) over placebo therapy.1

“Today’s results, especially when combined with those from the STEP-HFpEF trial, open a new chapter of targeting obesity as a new and effective treatment strategy in patients with obesity-related HFpEF, both with and without diabetes," Kosiborod added.3


  1. Kosiborod MN, Petrie MC, Borlaug BA, et al. Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes. N Engl J Med. Published online April 6, 2024. doi: 10.1056/NEJMoa2313917
  2. Campbell P. Semaglutide 2.4 mg shows benefit as treatment for heart failure with obesity. HCP Live. August 24, 2023. Accessed April 6, 2024.
  3. Saint Luke’s Health System. Semaglutide 2.4 mg demonstrates large reductions in heart failure related symptoms and physical limitations in people with obesity-related heart failure with preserved ejection fraction and type 2 diabetes. Saint Luke’s Health System. August 25, 2023. Accessed April 6, 2024.