# Tirzepatide vs Semaglutide for Heart Failure, With and Without Diabetes | This GLP A 217,920-person emulation found tirzepatide ahead of semaglutide on heart failure — relative risk 0.60 without diabetes against 0.82 with, but absolute differences of 0.9% and 1.5%. Publisher: This GLP Editorial Team Canonical: https://thisglp.com/research/bigger-relative-smaller-absolute Updated: 2026-09-18 Published: 2026-09-17 [← Research](https://thisglp.com/research) Evidence # Tirzepatide vs Semaglutide for Heart Failure, With and Without Diabetes In 217,920 matched adults, tirzepatide's heart failure risk ratio favored people without diabetes while the absolute risk difference favored people with it. Both come from the same table. [This GLP Editorial Team](https://thisglp.com/about)September 20267 min readUpdated September 2026 Heart failure at one year, tirzepatide vs semaglutide · risk ratio · absolute difference · with diabetes · 0.82 · 1.5% · without diabetes · 0.60 · 0.9% · Shorter bar wins on the left. Longer bar wins on the right. · They disagree about which group benefits more. **Research, not medical advice.** This GLP is independent and educational. Nothing here is a substitute for individualized care from a licensed clinician, and reading it creates no doctor–patient relationship. Talk to your own provider before starting, stopping, or changing any medication, peptide, or therapy. See our [methodology](https://thisglp.com/methodology) and [terms](https://thisglp.com/terms). ## Key takeaways - A target trial emulation matched 217,920 adults starting semaglutide or tirzepatide, splitting them by diabetes status: 48,507 pairs with, 60,453 pairs without. - Tirzepatide was associated with lower risk across every outcome measured at one and three years. - For heart failure at one year, the risk ratio was 0.82 with diabetes and 0.60 without — but the absolute risk differences were 1.5% and 0.9% respectively. - The relative figure favors the group without diabetes and the absolute figure favors the group with it. Both are correct. No trial has randomized semaglutide against tirzepatide on cardiovascular outcomes, so the comparison runs on claims data. A target trial emulation matched 217,920 adults starting one or the other and followed them for up to three years, reporting atrial fibrillation, heart failure and myocardial infarction as primary outcomes [\[1\]](https://thisglp.com/research/bigger-relative-smaller-absolute#ref-1). The same two drugs on a different endpoint are compared in [the liver comparison](https://thisglp.com/research/tirzepatide-vs-semaglutide-liver). Tirzepatide came out ahead on every outcome at both time points, and the associations strengthened over the three years. That is the finding most summaries will report, and taken at face value it is a straightforward win. One result, two numbers, opposite conclusions Heart failure at one year gave a risk ratio of 0.82 in people with diabetes and 0.60 in people without. Read relatively, the benefit is far larger for people without diabetes. The risk differences were 1.5 percentage points and 0.9 points respectively — read absolutely, the benefit is larger for people with diabetes. Nothing is contradictory here: a 40% reduction in a small risk removes fewer events than an 18% reduction in a large one. But a reader who meets only the 0.60 will draw the opposite conclusion from one who meets only the 1.5%. That asymmetry is worth internalizing because it recurs throughout this literature. Baseline risk determines how much a relative reduction is worth, which is why the same drug can look transformative in a high-risk population and marginal in a healthy one while behaving identically in both. The interaction tests here were significant for atrial fibrillation (P = 0.003), heart failure (P < 0.001) and myocardial infarction (P = 0.019), so the difference between the groups is not noise. The design carries the limitation that matters most. These are two drugs that entered the market at different times and get prescribed to different people for reasons a claims database records only partially, so the comparison is vulnerable to who was chosen for what rather than to what the drugs did. Propensity matching on recorded characteristics narrows that without closing it, the same caveat that applies to [the glaucoma comparison](https://thisglp.com/research/do-glp1-drugs-cause-glaucoma) and [the carpal tunnel cohort](https://thisglp.com/research/do-glp1-drugs-help-carpal-tunnel-syndrome), both of which also found tirzepatide ahead of its class on an unexpected endpoint. Read alongside the randomized evidence on weight in [the network meta-analysis of nineteen drugs](https://thisglp.com/research/the-best-losers-are-the-worst-tolerated), the picture is consistent in direction and much weaker in quality here. A pattern of tirzepatide outperforming across several unrelated outcomes could reflect a genuinely more effective drug, or it could reflect who gets prescribed the newer and more expensive option. ## Frequently asked Is tirzepatide better than semaglutide for the heart? This study found it associated with lower risk across every outcome, but it is observational rather than randomized. No trial has compared the two drugs head to head on cardiovascular outcomes. Why do the two heart failure numbers disagree? They measure different things. A risk ratio of 0.60 means a 40% relative reduction; a risk difference of 0.9% means fewer than one event avoided per hundred people. A large relative cut in a small risk prevents fewer events than a modest cut in a large one. Does diabetes status change the benefit? The interaction tests were significant for atrial fibrillation, heart failure and myocardial infarction, so yes — but which group benefits more depends on whether you read the relative or the absolute figures. ## Sources 1. \[1\] Azzam AY, Essibayi MA, Rai P, Salim HA, et al. (2026). Cardiovascular and Cerebrovascular Outcomes Risk Reduction Associated With Semaglutide vs Tirzepatide: A Target Trial Emulation JACC: Advances. [PMID 42489387](https://pubmed.ncbi.nlm.nih.gov/42489387/) ## Where to get it ### Best GLP-1 injections Every injectable seller we can verify, with the price each one publishes and an honest read of what the trials measured. 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