No current GLP-1 label lists heart failure as an approved use, so prescribing one for it would be off-label. SUMMIT (Tirzepatide): In heart failure with preserved ejection fraction and obesity, heart death or worsening heart failure happened in 9.9% on tirzepatide against 15.3% on placebo (hazard ratio 0.62). The difference came from worsening heart failure, 8.0% against 14.2%. Heart deaths were 8 people against 5, which the trial could not separate from chance (hazard ratio 1.58, confidence interval 0.52 to 4.83). ClinicalTrials.gov lists 36 trials of these medicines on it: 5 with posted results and 6 recruiting now.
Read from the registry and PubMed every day. The newest update here is Nov 2, 2026.
Each read in the paper's abstract on Nov 6, 2026. Trials differ in who took part and how long they ran.
Tirzepatide · 731 people · Better than the comparison · Placebo-controlled randomized trial
In heart failure with preserved ejection fraction and obesity, heart death or worsening heart failure happened in 9.9% on tirzepatide against 15.3% on placebo (hazard ratio 0.62). The difference came from worsening heart failure, 8.0% against 14.2%. Heart deaths were 8 people against 5, which the trial could not separate from chance (hazard ratio 1.58, confidence interval 0.52 to 4.83).
Semaglutide · 529 people · Better than the comparison · Placebo-controlled randomized trial
At 52 weeks, a symptom score (KCCQ, 0 to 100) rose 16.6 points on semaglutide 2.4 mg against 8.7 on placebo, and the 6-minute walk grew 21.5 m against 1.2 m.
A trial counts when the registry's conditions or title name this, and some study a related question, such as insulin sensitivity in people with the condition. A registered trial shows a question being asked, not that the answer is yes.
| Medicine | Trials | Posted results | Recruiting |
|---|---|---|---|
| Semaglutide | 16 | 2 | 4 |
| Liraglutide | 8 | 1 | 0 |
| Tirzepatide | 7 | 1 | 1 |
| Exenatide | 3 | 1 | 0 |
| MariTide | 1 | 0 | 1 |
| Mazdutide | 1 | 0 | 0 |
Latest phases and largest trials first. Each result is the first primary outcome as its sponsor posted it to the registry, which is not peer review.
| Trial | Medicine | Phase | People | Result |
|---|---|---|---|---|
| NCT04847557A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial | Tirzepatide | Phase 3 | 731 | Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) (Score on a scale), Baseline, Week 52. Tirzepatide - MTD: 19.51; Placebo: 12.68. |
| STEP HFpEF DMResearch Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes | Semaglutide | Phase 3 | 617 | Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score (Score on a scale), Baseline (week 0), end of treatment (week 52). Semaglutide 2.4 mg: 14.4; Placebo: 7.6. |
| STEP-HFpEFResearch Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity | Semaglutide | Phase 3 | 529 | Change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (Score on a scale), From baseline (week 0) to end of treatment (week 52). Semaglutide 2.4 mg: 16.8; Placebo: 10.3. |
| NCT00799435Evaluating the Use of Exenatide in People With Type 2 Diabetes and Diastolic Heart Failure | Exenatide | Phase 4 | 2 | Change in Aortic Stiffness, as Measured by the Change in the Mean Aortic Pulse Wave Velocity (m/sec), Measured at Week 12, Baseline Pulse Wave Velocity. Usual Care: 11.4; Exenatide: 9.3. |
| FIGHTFunctional Impact of GLP-1 for Heart Failure Treatment (FIGHT) | Liraglutide | Phase 2 | 300 | Global Ranking of Predefined Events (rank), Randomization to 180 days. Liraglutide: 145.5; Placebo: 155.7. |
The registry page names each site and who can enroll. Ask your clinician before joining one.
| Trial | Medicine | Phase | Expected to finish |
|---|---|---|---|
| Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity | MariTide | Phase 3 | Sep 29, 2030 |
| Multifactorial Intervention to Reduce Cardiovascular Disease in Type 1 Diabetes | Semaglutide | Phase 3 | Jul 1, 2029 |
| Tailored Exercise Training Study Among Adults With HFpEF | Semaglutide | Phase 2/3 | Dec 30, 2026 |
| Effect of Weight Loss on Physical and Cardiac Performance in People With Obesity and Heart Failure | Semaglutide | Phase 2/3 | Dec 30, 2027 |
| Epicardial Adipose Tissue Composition and Heart Failure With Preserved Ejection Fraction | Semaglutide | Phase 4 | Dec 2029 |
| Incretin Therapies in Obesity-related HFpEF | Tirzepatide | Phase 4 | Apr 2030 |
Meta-analysis · J Clin Endocrinol Metab · Oct 13, 2026 · Eisa N et al.
Meta-analysis · Drugs · Sep 26, 2026 · Yuan Y et al.
Meta-analysis · Nutr Metab Cardiovasc Dis · Sep 8, 2026 · AlAraibi AJ et al.
Meta-analysis · Am J Cardiovasc Drugs · Jul 10, 2026 · Tristan CD et al.
Randomized trial · Cureus · Jul 7, 2026 · Patel J et al.
Meta-analysis · J Clin Med · Jun 9, 2026 · Christophides T et al.
Listed from Europe PMC as published, newest first. A listing here is not a judgement of a study's quality or a recommendation.
Written from each source's own record as it changes. Every change on GLPcompare
SUMMIT (Tirzepatide, 731 people): In heart failure with preserved ejection fraction and obesity, heart death or worsening heart failure happened in 9.9% on tirzepatide against 15.3% on placebo (hazard ratio 0.62). The difference came from worsening heart failure, 8.0% against 14.2%. Heart deaths were 8 people against 5, which the trial could not separate from chance (hazard ratio 1.58, confidence interval 0.52 to 4.83).
Not in any current label we read. A prescriber can still use a medicine off-label, but insurance often limits coverage to approved uses, so ask your plan.
Semaglutide, with 16 registered trials on it, then Liraglutide with 8. More trials do not mean better results: read what each posted.
6 trials are recruiting on ClinicalTrials.gov now, listed below with their registry pages, which name each site and who can enroll.