Category: Clinical Trials & Real-World Evidence
Written and Reviewed By: Pharmacally Medical News Desk
At European Society of Cardiology Congress 2025 in Madrid happening between August 29 to 1 September 2025, Novo Nordisk reported that Wegovy (semaglutide 2.4 mg) was linked to a 57% lower risk of heart attack, stroke, or death compared with tirzepatide in people with obesity and established cardiovascular disease who do not have diabetes, based on a large U.S. real-world analysis called STEER. STEER study was focused on to investigate the risk of major adverse cardiovascular events (MACE) with Wegovy® (semaglutide) 2.4 mg and compared with tirzepatide treatment in people with overweight or obesity and established CVD without diabetes.
As obesity is directly linked to cardiovascular diseases risk hence cardiovascular protection is now by default the subject of study for every obesity pharmacotherapy. The randomized SELECT trial already showed that semaglutide 2.4 mg cuts major cardiovascular events by 20% versus placebo in patients with overweight or obesity and prior CVD, without diabetes. STEER study asks a practical question clinicians face every week: what happens when patients receive semaglutide vs tirzepatide in routine care.
Study Design
The STEER study was designed as a retrospective analysis using the U.S. Komodo Research database to evaluate cardiovascular outcomes in people with obesity and established cardiovascular disease that did not have diabetes. It included adults aged 45 years or older and compared new users of Wegovy (semaglutide 2.4 mg) with new users of tirzepatide. To ensure a fair comparison, 10,625 patients starting Wegovy were matched with 10,625 patients starting tirzepatide. The main outcomes were major adverse cardiovascular events (MACE), measured in two ways: a three-point definition including nonfatal heart attack, nonfatal stroke, and death from any cause, and a broader five-point definition that also included hospitalization for heart failure and coronary revascularization. The study examined results both in an “on-treatment” analysis, which excluded patients with treatment gaps longer than 30 days, and in an “all-treated” analysis, which included everyone regardless of adherence.
Results
The results showed that Wegovy was associated with a lower risk of serious cardiovascular events compared with tirzepatide. In the on-treatment analysis, Wegovy users had a 57% lower risk of experiencing heart attack, stroke, or death, with 15 events reported among Wegovy patients compared to 39 events in the tirzepatide group during an average follow-up of just under four months. In the broader all-treated analysis, Wegovy was still linked with a 29% lower risk, with 56 events occurring in the Wegovy group and 83 in the tirzepatide group over an average of about eight months of follow-up. Although the study’s follow-up period was relatively short and the number of events small, the findings support semaglutide potential cardiovascular benefit in patients with obesity and existing heart disease.
What is message of STEER study from ESC 2025
Results are consistent with SELECT trial: The real-world evidence from STEER study for semaglutide is aligns with SELECT’s placebo-controlled 20% MACE reduction, strengthening the case that semaglutide cardiovascular benefit is clinically significant outside trials also.
Molecule vs class: In STEER study Novo Nordisk observed that Wegovy® had greater cardiovascular improvements compared to Tirzepatide, so Novo Nordisk claims that the benefit should not be applied to across all GLP-1 or GIP/GLP-1 agents; it is specific to Wegovy (semaglutide) only.
Short follow-up and few events: Average follow-up was only a few months (3.8 months for semaglutide and 4.3 months for Tirzepatide) and the absolute number of events was small. It should be emphasized that short observations can make the results more sensitive to hidden differences between groups and possible errors in event recording.
For patients with obesity and established CVD without diabetes, semaglutide 2.4 mg remains the best-supported option for cardiovascular risk reduction today, backed by randomized outcomes evidence and now favorable real-world comparative data versus tirzepatide.
Safety Profile of Semaglutide
Wegovy carries an important safety warning that should be considered when prescribing.
The 2.4 mg semaglutide injection includes a Boxed Warning for possible thyroid tumors, including cancer, and it must not be used in people with a personal or family history of medullary thyroid carcinoma (MTC) or in those with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
Frequently reported side effects are gastrointestinal, such as nausea, vomiting, diarrhea, constipation, stomach pain, and bloating, belching, and upset stomach. Other common effects include headache, fatigue, dizziness, heartburn, runny nose or sore throat, and symptoms of stomach flu. In patients with type 2 diabetes, low blood sugar can also occur.
These risks underline the importance of patient selection, careful monitoring about tolerability and safety when initiating therapy with semaglutide.
In conclusion, the STEER study presented at ESC 2025 provides supportive real-world evidence that semaglutide 2.4 mg (Wegovy) may offer significant cardiovascular protection in people with obesity and established heart disease, even when compared against another active treatment such as tirzepatide. The findings were consistent with SELECT trial and strengthen the position of semaglutide as the most evidence-backed option for reducing cardiovascular risk in this population. While the study’s short follow-up and limited number of events highlights the need for longer-term confirmation.
References
Novo Nordisk’s Wegovy® cuts risk of heart attack, stroke or death by 57% compared to tirzepatide in real-world study of people with obesity and cardiovascular disease, PR Newswire, 31 Aug 2025, https://www.prnewswire.com/news-releases/novo-nordisks-wegovy-cuts-risk-of-heart-attack-stroke-or-death-by-57-compared-to-tirzepatide-in-real-world-study-of-people-with-obesity-and-cardiovascular-disease-302542590.html
Lauren Wilson; Zhenxiang Zhao; Victoria Divino et al, Semaglutide is associated with lower risk of cardiovascular events compared with tirzepatide in patients with overweight or obesity and ASCVD and without diabetes in routine clinical practice, Presentation for ESC-2025, https://sciencehub.novonordisk.com/congresses/esc2025/wilson.html
ESC 2025: Novo Nordisk’s Wegovy superior to Zepbound in reducing CV events, Clinical Trial Arena, 01 September 2025, https://www.clinicaltrialsarena.com/news/esc-2025-novo-nordisks-wegovy-superior-to-zepbound-in-reducing-cv-events/