Closing
Do GLP-1 receptor agonists improve cardiovascular events versus placebo?
Mostly studied in heart failure. Also asked against other treatments.
Not modeled yetTrial evidence exists, but no mechanistic model yetWithout a model there is no decisive experiment to propose. Help build it. →
Where the evidence stands
A coin flip. So far, the results disagree.
NoUnsureYes
- Belief
- 0.50 (range 0.00–0.55)
- Trials for
- 7
- Trials against
- 3
- Inconclusive
- 1
Already under way
- Comparative Effectiveness of Oral Semaglutide vs Sitagliptin Among Individuals With Heart Failure With Preserved Ejection Fraction (STEP-HFpEF DM ORAL)NCT07390110 · active not recruiting · started 2026
- Comparative Effectiveness of Tirzepatide vs Semaglutide in Participants With Type 2 Diabetes and Heart Failure With Preserved Ejection FractionNCT06980623 · active not recruiting · started 2025
- Multifactorial Intervention to Reduce Cardiovascular Disease in Type 1 DiabetesNCT06082063 · recruiting · started 2024
- Effect of Weight Loss on Physical and Cardiac Performance in People With Obesity and Heart FailureNCT06423599 · recruiting · started 2024
The evidence so far
- Registered trials
- 102
- With posted results
- 44
- Published papers
- 33
Of 61 decided analyses: 19 favor glp-1 receptor agonists, 34 find no difference, 8 favor the comparator.
Papers
- Effects of Semaglutide With or Without Concomitant Mineralocorticoid Receptor Antagonist Use in Participants With Type 2 Diabetes and Chronic Kidney Disease: A FLOW Trial Prespecified Secondary Analysis.Trial report · 2025
- Cardiovascular outcomes of liraglutide in patients with type 2 diabetes: A systematic review and meta-analysis.Meta-analysis / systematic review · 2019
- Achieving the composite endpoint of glycated haemoglobin <7.0%, no weight gain and no hypoglycaemia in the once-weekly dulaglutide AWARD programme.Meta-analysis / systematic review · 2016
- Effect of semaglutide on arrhythmic, major cardiovascular, and renal outcomes in patients with overweight or obesity: a systematic review and meta-analysis.Meta-analysis / systematic review · 2025
- GLP-1RAs and tirzepatide may reduce heart failure risk in obese but not in non-obese patients with cardiovascular or renal disease: A systematic review and meta-analysis.Meta-analysis / systematic review · 2026
- Effect of semaglutide on arrhythmic, major cardiovascular, and microvascular outcomes in patients with type 2 diabetes: a systematic review and meta-analysis.Meta-analysis / systematic review · 2025
Trials
- A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 DiabetesNCT02692716 · 10 posted results
- Cardiovascular Outcomes, and Mortality in Danish Patients With Type 2 Diabetes Who Initiate Empagliflozin Versus Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA): A Danish Nationwide Comparative Effectiveness Study [EMPLACEtm]NCT03993132 · 8 posted results
- A Phase 4, Randomized, Open-Label, Active-Controlled Study to Investigate the Efficacy and Safety of Switching From Weekly Dulaglutide to Weekly Tirzepatide in Adults With Type 2 DiabetesNCT05564039 · 1 posted result
- An Exploratory Phase 2, Randomised, Double-blind, Placebo-controlled, and Open-label Active Comparator Study to Evaluate the Effect of MEDI0382 on Hepatic Glycogen Metabolism in Overweight and Obese Subjects With Type 2 Diabetes Mellitus.NCT03555994 · 3 posted results
- Liraglutide in Acute Minor Ischemic Stroke or High-risk Transient Ischemic Attack Patients With Type 2 Diabetes Mellitus: A Prospective, Multicenter, Randomized, Blank-controlled,Blinded End-point Study.NCT03948347 · 1 posted result
- A Long-term, Multi-centre, International, Randomised Double-blind, Placebo-controlled Trial to Determine Liraglutide Effects on Cardiovascular EventsNCT01179048 · 28 posted results
- A Long-term, Randomised, Double-blind, Placebo-controlled, Multinational, Multi-centre Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN™ 6 - Long-term Outcomes)NCT01720446 · 13 posted results
- The Effect of Dulaglutide on Major Cardiovascular Events in Patients With Type 2 Diabetes: Researching Cardiovascular Events With a Weekly INcretin in Diabetes (REWIND)NCT01394952 · 6 posted results