Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA1c levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial
Authors' conclusion
Semaglutide 2.4 mg improved heart failure-related symptoms and physical limitations, and reduced bodyweight in patients with obesity-related HFpEF and type 2 diabetes, all independently of baseline HbA1c, and resulted in lower rates of hypoglycaemia than placebo, despite a well controlled baseline HbA1c and broad use of concomitant glucose-lowering medications.
Study context
- Population
- Adults ≥18 years with HFpEF (LVEF ≥45%), T2D and obesity (BMI ≥30 kg/m²); mean age 68.4 years, 44% female
- Participants
- 616 adults
- Comparison
- Semaglutide 2.4 mg once weekly vs placebo across baseline HbA1c categories
- Semaglutiden = 310
- Placebon = 306reference
- Primary endpoint
- Dual: change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and bodyweight percentage from baseline, by baseline HbA1c category (low <6.5%, medium 6.5% to <7.5%, high ≥7.5%)
- Follow-up
- 52 weeks
Methodological detailsdouble-blind, placebo-controlled, multicentre (108 sites, 16 countries), randomised 1:1, stratified by baseline BMI, subgroup analysis by baseline HbA1c, Median follow-up 401 days (IQR 400-405)
- Double-blind
- Placebo-controlled
- Multicentre (108 sites, 16 countries)
- Randomised 1:1, stratified by baseline BMI
- Subgroup analysis by baseline HbA1c
- Median follow-up 401 days (IQR 400-405)
Primary result
As reported in the abstract
Change in KCCQ-CSS by baseline HbA1c
Semaglutide vs PlaceboEstimate (95% CI)P value
12.4 vs 5.7 points
mean difference (low HbA1c) 6.7 points(1.6–11.8)
14.5 vs 8.5 points
mean difference (medium HbA1c) 6.0 points(0.9–11.1)
14.5 vs 4.8 points
mean difference (high HbA1c) 9.6 points(3.5–15.7)
P = 0.64; ptrend=0.46for interactionFurther findings
| Outcome | Semaglutide | Placebo | Mean difference (low HbA1c) (95% CI) | |
|---|---|---|---|---|
| Change in bodyweight (%) by baseline HbA1c (dual primary) · 52 weeksIntention to treat | −10.8 | −3.3% | −7.5% (−9.4 to −5.6) | |
| −10−505Difference (linear scale) |
| Outcome | Semaglutide | Placebo | Estimate | P value | |
|---|---|---|---|---|---|
| Change in bodyweight (%) by baseline HbA1c (dual primary) · 52 weeksIntention to treat | −9.6% | −3.3% | mean difference (medium HbA1c) −6.3 % (95% CI −8.2 to −4.4) | ||
| Change in bodyweight (%) by baseline HbA1c (dual primary) · 52 weeksIntention to treat | −8.6% | −3.6% | mean difference (high HbA1c) −5.0 % (95% CI −7.2 to −2.7) | P for interaction = 0.22; ptrend=0.083 | |
| −10−505Difference, % (linear scale) |
Safety
Hypoglycaemia
Events Semaglutide 70 · Placebo 90
Events per 100 person-years Semaglutide 22.9 · Placebo 29.5
- Hypoglycaemia: participants who received ≥1 dose
Original publication
Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA1c levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. Published 20 January 2025. doi:10.
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