SCORE analysis of semaglutide 2.4 mg demonstrated risk reduction in cardiovascular events in a real-world setting

• Building on results of the landmark SELECT trial, SCORE shows cardiovascular (CV) risk reduction with use of semaglutide 2.4 mg in a real-world environment¹
• SCORE is a retrospective, observational analysis of 27,963 patients in the U.S. with obesity or overweight and established cardiovascular disease¹

MISSISSAUGA, ON, March 31, 2025 /CNW/ - Novo Nordisk presented new data from the retrospective, observational SCORE study that assessed treatment with semaglutide 2.4 mg and the risk of major adverse cardiovascular events (MACE) in adults with overweight or obesity and established cardiovascular disease (CVD).¹ The real-world analysis was presented at the American College of Cardiology 74th Annual Scientific Session and Expo (ACC.25).¹

Compared with non-users, semaglutide 2.4 mg use was associated with a significantly lower risk of revised MACE-3 composite endpoint (heart attack, stroke, or all-cause death) by 57% (HR: 0.43; 95% CI: 0.31-0.61; p < 0.001).¹ Revised MACE-3 occurred in 42 (0.45%) of the 9,321 patients in the semaglutide 2.4 mg group and 175 (0.94%) of the 18,642 patients in the non-user group.¹ The mean follow-up duration was 7.1 months for semaglutide users and 6.4 months for non-users.¹

Compared with non-users, semaglutide 2.4 mg use was associated with a significantly lower risk of revised MACE-5 composite endpoint (heart attack, stroke, hospitalization for heart failure (HF), evidence of a coronary revascularization procedure, or all-cause death) by 45% (HR: 0.55; 95% CI: 0.43-0.70; p < 0.001).¹ Revised MACE-5 occurred in 88 (0.94%) of the 9,321 patients in the semaglutide 2.4 mg group and 288 (1.54%) of 18,642 patients in the non-user group.¹

SCORE results were consistent across a variety of CV endpoints, including death. Compared with non-users, semaglutide 2.4 mg use was also associated with significantly lower risk of hospitalization for HF, CV-related death, and all-cause death.¹

Real-world study data can provide valuable insights into how treatments work outside of controlled clinical trial settings. Real-world data analyses also have several limitations; results may reflect residual unmeasured confounding; while associations can be demonstrated, causal relationships cannot be definitively established. The relatively recent approval of semaglutide 2.4 mg limited follow-up duration, restricting the assessment of long-term benefits.¹ Additionally, use of retrospective claims data may exclude patients with intermittent coverage or underserved populations, potentially limiting generalizability.¹

Over 8 million Canadian adults are living with obesity and many require support to effectively manage their condition.²  The prevalence of obesity, which increases the risk of serious chronic illness including heart disease, has grown over the last two decades.^3,4 Canadians living with obesity are more than twice as likely to have heart disease than those with a healthy weight.⁵

About semaglutide 2.4 mg
In 2024 in Canada, Wegovy^® (semaglutide injection) was approved to reduce the risk of non-fatal myocardial infarction in adults with established cardiovascular disease and BMI equal to or greater than 27 kg/m².  It is the first Health Canada approved treatment to support both chronic weight management and to reduce the risk of non-fatal MI.⁶

About real-world evidence (RWE) SCORE study
Real-world studies are conducted to complement randomized control trials, which are the gold standard for evaluating the safety and efficacy of a treatment.⁷ The SCORE study analyzed MACE outcomes among semaglutide 2.4 mg users and non-users in real-world clinical practice in the U.S.¹ Analysis was based on a database with administrative medical and pharmacy claims linked to clinical and laboratory measurements that is nationally representative of the U.S. population and a sample of patients who met similar inclusion criteria as in the SELECT trial.¹

The primary objectives for SCORE were to compare revised MACE-5 (heart attack, stroke, hospitalization for heart failure (HF)) and revised MACE-3 (heart attack, stroke, or all-cause death) in semaglutide 2.4 mg users compared to non-users in a time-to-first event analysis. This differed from the SELECT trial, whereby the primary MACE composite endpoint comprised of non-fatal heart attack, non-fatal stroke, or cardiovascular (CV) death.

Patients aged ≥ 45 years with overweight or obesity (diagnosis or BMI ≥ 27 kg/m²) and established CVD (prior heart attack, ischemic stroke, or peripheral arterial disease (PAD)) but no diabetes were placed into two study groups, including patients who initiated semaglutide 2.4 mg (n=9,321), and non-users who did not initiate semaglutide 2.4 mg (n=18,642).¹

Each semaglutide 2.4 mg user was matched using propensity scoring to two non-users to balance baseline characteristics including: demographics, overweight/obesity status, BMI, comorbidities, procedures, medication use, and HRU. Patient characteristics among matched patients were well- balanced.¹

About SELECT cardiovascular outcomes trial
SELECT was a multicenter, randomized, double-blind, placebo-controlled, event-driven superiority trial designed to evaluate the efficacy of semaglutide 2.4 mg versus placebo as an adjunct to cardiovascular standard of care for reducing the risk of major adverse cardiovascular events (cardiovascular death, non-fatal heart attack, or non-fatal stroke) in adults with established CVD with overweight or obesity with no prior history of diabetes.⁸  In SELECT, established CVD was defined as a prior heart attack, prior stroke, or symptomatic PAD.⁸ The trial, initiated in 2018, enrolled 17,604 adults and was conducted in 41 countries at more than 800 investigator sites.⁸

About Novo Nordisk
Novo Nordisk is a leading global healthcare company founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 76,300 people in 80 countries and markets its products in around 170 countries. For more information, visit novonordisk.ca, Facebook, Instagram, X, LinkedIn and YouTube.

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^1	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.
^2	Statistics Canada. An overview of weight and height measurements on World Obesity Day. https://www.statcan.gc.ca/o1/en/plus/5742-overview-weight-and-height-measurements-world-obesity-day
^3	Statistics Canada. An overview of weight and height measurements on World Obesity Day. https://www.statcan.gc.ca/o1/en/plus/5742-overview-weight-and-height-measurements-world-obesity-day
^4	Twells LK, Janssen I, Kuk JL. Canadian Adult Obesity Clinical Practice Guidelines: Epidemiology of Adult Obesity. https://obesitycanada.ca/guidelines/epidemiology
^5	Heart and Stroke Foundation. Healthy weight and waist. https://www.heartandstroke.ca/healthy-living/healthy-weight/healthy-weight-and-waist
^6	Novo Nordisk Canada Inc. (2025, March 11). Wegovy^® Product Monograph.  https://www.novonordisk.ca/content/dam/nncorp/ca/en/products/Wegovy-product-monograph.pdf
^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(11):1763-1774. doi:10.1007/s12325-018-0805-y.
^8	Lincoff MA, Brown-Frandson K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221-2232.

SOURCE Novo Nordisk Canada Inc.

Contact for further information: Novo Nordisk Canada, Kate Hanna, 905-301-7334, [email protected]; Amy Snow, 647-202-6367, [email protected]; Jaclyn Crawford, 647-201-6817, [email protected]