In new findings unveiled at the European Society of Cardiology (ESC) Congress in Madrid, Danish pharmaceutical powerhouse Novo Nordisk has revealed compelling real-world evidence indicating that its leading weight-loss medication, Wegovy (semaglutide), reduces the combined risk of heart attack, stroke or death by 57 per cent compared with rival drug tirzepatide (marketed as Mounjaro and Zepbound) in adults with obesity and established cardiovascular disease, but without diabetes.
This observational analysis, dubbed the STEER study, examined anonymised data from over 21,000 US adults drawn from the Komodo Research database between January 2016 and January 2025. Each cohort, Wegovy users and tirzepatide users, contained 10,625 matched individuals, ensuring comparability via propensity-score matching.
- For patients with continuous treatment (no gaps longer than 30 days), those on Wegovy experienced a 57% greater reduction in the risk of heart attack, stroke or death from any cause compared with those on tirzepatide. Incidents were recorded at just 0.1% (15 events) in the Wegovy group versus 0.4% (39 events) in the tirzepatide group, across average follow-ups of 3.8 months and 4.3 months, respectively.
- When including all treated patients, regardless of adherence, Wegovy still conferred a significant 29% risk reduction. There were 56 events (0.5%) for Wegovy users, compared with 83 events (0.8%) among tirzepatide users, over longer average follow-ups of 8.3 months and 8.6 months.
These observations underscore that cardiovascular (CV) benefits seen with Wegovy may be molecule-specific to semaglutide rather than shared across the broader GLP-1 or dual GIP/GLP-1 receptor agonist classes, a pivotal distinction in therapeutic decisions.
Novo Nordisk’s Anna Windle, Senior Vice President for Clinical Development, emphasised that real-world studies like STEER offer vital insights into how treatments perform outside clinical trial control and hint at the advantages of Wegovy beyond weight loss alone.
The STEER findings build on results from the SELECT cardiovascular outcomes trial. SELECT was a large, randomised, placebo-controlled phase III study involving 17,604 participants aged 45 and over, with overweight or obesity and established cardiovascular disease but without diabetes.
In SELECT, Wegovy demonstrated a 20% relative reduction in major adverse cardiovascular events (MACE), which included CV death, non-fatal myocardial infarction and non-fatal stroke, compared with placebo, over approximately 40 months of follow-up.
These consistent findings reinforce Wegovy’s emerging role not just in weight management, but also in primary and secondary prevention of cardiovascular events.
However, STEER’s non-randomised, retrospective design means it cannot definitively establish cause and effect. Potential unmeasured confounding, coding errors, and shorter follow-up durations, especially in the continuous-treatment subgroup, caution against over-interpretation of the magnitude of benefit.
Moreover, semaglutide (Wegovy 2.4 mg weekly) carries a boxed warning regarding possible thyroid tumours, including medullary thyroid carcinoma, and should not be used in individuals with a personal or family history of medullary thyroid cancer or MEN 2 syndrome.
Obesity continues to be a pressing concern, with associated cardiovascular conditions a major cause of morbidity and mortality. While GLP-1 agonists like Wegovy and tirzepatide are increasingly prescribed, access remains limited under NHS guidelines, and NICE has yet to broaden indications significantly.
These fresh data could inform policy discussions. Experts have urged accelerated NHS rollout of such therapies, not only for weight control but also as primary or secondary prevention tools against heart attack and stroke, a move that could substantially reduce long-term NHS burdens.
The STEER study adds to a growing body of evidence that not all weight-loss drugs offer equivalent cardiovascular benefits. In particular, Wegovy (semaglutide) appears to hold a distinct advantage over tirzepatide in reducing serious adverse cardiovascular outcomes in people with obesity and heart disease.
While more robust and longer-term data are warranted, especially from randomised trials and real-world follow-up, these findings spotlight semaglutide’s evolving status as a dual-benefit therapy, targeting both metabolic and cardiovascular health.
