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

• Compared with tirzepatide, Wegovy^® (semaglutide) 2.4 mg showed a significant 57% greater reduction in the risk of heart attack, stroke or death from any cause, in people with overweight or obesity and cardiovascular disease (CVD) while on treatment¹
• Similarly, the study showed a significant 29% reduction in the risk for heart attack, stroke and death from any cause in the Wegovy^® users compared with tirzepatide users in all treated people, regardless of any gaps in their treatment¹
• The findings support growing evidence that the established CV benefit seen with Wegovy^® is specific to the semaglutide molecule and therefore cannot be generalized to the GLP-1 or GIP/GLP-1-receptor agonist classes¹

PLAINSBORO, N.J., Aug. 31, 2025 /PRNewswire/ -- Novo Nordisk today presented data from the STEER real-world study of evidence gathered from actual patient experiences at the European Society of Cardiology (ESC) Congress 2025 in Madrid, Spain. The STEER study investigated the risk of major adverse cardiovascular events (MACE) with Wegovy^® (semaglutide) 2.4 mg compared with tirzepatide treatment in people with overweight or obesity and established CVD without diabetes.¹

Compared with tirzepatide, Wegovy^® showed a significant 57% greater risk reduction for heart attack, stroke and cardiovascular-related death or death from any cause, in people with overweight or obesity and CVD, while on treatment with no treatment gaps more than 30 days. There were 15 (0.1%) of these cardiovascular events recorded with Wegovy^®, and 39 events (0.4%) were recorded with tirzepatide. The average follow-up duration was 3.8 months for the Wegovy^® group and 4.3 months for the tirzepatide group.¹ 

In all treated people, regardless of any gaps in their treatment, Wegovy^® showed a significant 29% risk reduction for heart attack, stroke and death from any cause compared with tirzepatide (over an average follow-up of 8.3 months for Wegovy^® and 8.6 months for tirzepatide). There were 56 (0.5%) of these cardiovascular events recorded with Wegovy^®, and 83 events (0.8%) were recorded with tirzepatide.¹

"In the STEER study, patients using Wegovy^® had greater cardiovascular improvements compared to tirzepatide, indicating that the same CV benefit cannot be generalized across other molecules in the GLP-1 or GIP/GLP-1 classes and may come specifically from the semaglutide molecule," said Anna Windle, Senior Vice President, Clinical Development, Medical and Regulatory Affairs at Novo Nordisk. "Real-world studies, like STEER, provide us with important insights into how treatments may serve patients outside of controlled clinical trials as we continue to learn more about the benefits of Wegovy^® beyond weight management."

Additionally, in all treated people, regardless of any gaps in their treatment, people treated with Wegovy^® experienced fewer events of heart attack, stroke and cardiovascular-related death than people treated with tirzepatide.¹

It is important to note that semaglutide injection 2.4 mg contains a Boxed Warning for possible thyroid tumors, including cancer and should not be used in those with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). The most common side effects include nausea, diarrhea, vomiting, constipation, stomach (abdomen) pain, headache, tiredness (fatigue), upset stomach, dizziness, feeling bloated, belching, low blood sugar in people with type 2 diabetes, gas, stomach flu, heartburn, and runny nose or sore throat.

About obesity and cardiovascular disease
Every year, almost 21 million people die from CVD, which is the leading cause of disability and death worldwide.² Obesity directly leads to cardiovascular morbidity, mortality and hospitalization.^3,4 While cardiovascular mortality has decreased over the past two decades, obesity-related cardiovascular deaths have increased significantly, with two in three obesity-related deaths being linked to CVD.^5,6

About the real-world STEER study
Real-world studies of evidence gathered from actual patient experiences can complement randomized control trials, which are the gold standard for evaluating the safety and efficacy of a treatment.⁷ Real-world data analyses also have several limitations; while associations can be demonstrated, causal relationships cannot be definitively established. Results may reflect potential unmeasured confounding, the relatively recent approval of both treatments limited follow-up duration, and administrative claims data may be subject to coding inaccuracies.

STEER was a retrospective, observational real-world study, evaluating the efficacy of Wegovy^® (semaglutide) 2.4 mg versus tirzepatide in lowering the risk of MACE in US adults with overweight or obesity and established CVD with no prior history of diabetes, with a primary outcome measure of revised 5-point MACE (heart attack, stroke, hospitalization for heart failure, coronary revascularization, and death from any cause) and revised 3-point MACE (heart attack, stroke and death from any cause). Non-revised 5-point and 3-point MACE was also studied, which included cardiovascular-related death rather than death from any cause.¹

The study included people from the US Komodo Research database (January 1, 2016 to January 31, 2025) aged ≥45 years and started treatment with Wegovy^® or tirzepatide on or after May 13, 2022. Each treatment group comprised 10,625 people. To ensure both groups were comparable, researchers used propensity score matching to compare Wegovy^® users and tirzepatide users with similar characteristics. After matching, characteristics were well-balanced between the treatment groups.¹

The main analysis included all people who started treatment, regardless of any gaps in their therapy, while a sensitivity analysis evaluated outcomes only in people who did not have any gaps in their treatment lasting more than 30 consecutive days.¹

About the SELECT trial and SCORE real-world study
SELECT was a randomized, double-blind, parallel-group, placebo-controlled trial designed to evaluate the efficacy of Wegovy^® (semaglutide) 2.4 mg versus placebo as an adjunct to standard of care for the prevention of MACE in people with overweight or obesity and established CVD with no prior history of diabetes. People included in the trial were aged ≥45 years with a body mass index (BMI) of ≥27 kg/m².⁸

The primary objective of the SELECT trial was to demonstrate the superiority of Wegovy^® compared to placebo with respect to reducing the incidence of 3-point MACE consisting of cardiovascular death, non-fatal heart attack (myocardial infarction) or non-fatal stroke.⁸

SCORE was a real-world study in the US that analyzed MACE outcomes among Wegovy^® (semaglutide) 2.4 mg users and non-users in real-world clinical practice, who met similar inclusion criteria as in the SELECT trial and were aged ≥45 years with overweight or obesity and established CVD without diabetes.⁹

About Wegovy^®
WEGOVY^® (semaglutide) injection 2.4 mg is an injectable prescription medicine used with a reduced calorie diet and increased physical activity.¹⁰

• to reduce the risk of major cardiovascular events such as death, heart attack, or stroke in adults with known heart disease and with either obesity or overweight
• that may help adults and children aged 12 years and older with obesity, or some adults with excess weight (overweight) who also have weight-related medical problems to lose excess body weight and keep the weight off

Wegovy^® contains semaglutide and should not be used with other semaglutide-containing products or other GLP-1 receptor agonist medicines.

It is not known if Wegovy^® is safe and effective:

• to reduce the risk of major cardiovascular events (death, heart attack, or stroke) in children under 18 years
• for the treatment of long-term weight loss in children under 12 years

About Novo Nordisk
Novo Nordisk is a leading global healthcare company that's been making innovative medicines to help people with diabetes lead longer, healthier lives for more than 100 years. This heritage has given us experience and capabilities that also enable us to drive change to help people defeat other serious chronic diseases such as obesity, rare blood, and endocrine disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term, and do business in a financially, socially, and environmentally responsible way. With a US presence spanning 40 years, Novo Nordisk US is headquartered in New Jersey and employs over 10,000 people throughout the country across 12 manufacturing, R&D and corporate locations in eight states plus Washington DC. For more information, visit novonordisk-us.com, Facebook, Instagram, and X.

Novo Nordisk is committed to the responsible use of our semaglutide-containing medicines which represent distinct products with different indications, dosages, prescribing information, titration schedules, and delivery forms. These products are not interchangeable and should not be used outside of their approved indications. Learn more at semaglutide.com.

References

1. Wilson L, Zhao Z, Divino V, 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. Oral presentation presented at the European Society of Cardiology Congress 2025; 29 August–01 September 2025; IFEMA Madrid, Madrid, Spain.
2. World Heart Federation. World Heart Report 2023: Confronting the World's Number One Killer. Available at: https://world-heart-federation.org/wp-content/uploads/World-Heart-Report-2023.pdf. Last accessed: July 2025.
3. Haidar A and Horwich T. Obesity, Cardiorespiratory Fitness, and Cardiovascular Disease. Curr Cardiol Rep. 2023;25:1565–1571.
4. Zizza C, Herring AH, Stevens J, et al. Length of Hospital Stays Among Obese Individuals. Am J Public Health. 2004;94:1587–1591.
5. Raisi-Estabragh Z, Kobo O, Mieres JH, et al. Racial Disparities in Obesity-Related Cardiovascular Mortality in the United States: Temporal Trends From 1999 to 2020. J Am Heart Assoc. 2023;12: e028409.
6. Collaborators GBDO, Afshin A, Forouzanfar MH, et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med. 2017;377:13–27.
7. Blonde L, Khunti K, Harris SB, et al. Interpretation and Impact of Real-World Clinical Data for the Practicing Clinician. Adv Ther. 2018;35:1763–1774.
8. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389:2221–2232.
9. Zhao Z, Song J, Faurby M, et al. Lower Risk of MACE and All-Cause Death in Patients Initiated on Semaglutide 2.4 mg in Routine Clinical Care: Results from the SCORE Study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World). Moderated poster presentation presented at the American College of Cardiology Scientific Session & Expo 2025; 29–31 March 2025; McCormick Place Convention Center, Chicago, US. Presentation 947-13.
10. Wegovy^® Prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/215256s015lbl.pdf. Last accessed: August 2025.

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