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SCORE analysis of semaglutide 2.4 mg demonstrated 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 with obesity or overweight and established cardiovascular disease¹

, /PRNewswire/ -- Today, 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 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

"Real-world analyses such as SCORE complement randomized controlled trials by offering healthcare professionals additional information about how therapies perform in routine clinical practice as they partner with patients on individualized treatment decisions," said Jason Brett, MD, Acting Principal Medical Head at Novo Nordisk Inc. "Our mission is to drive change in how obesity is seen and treated, and the real-world evidence from SCORE provides actionable insights that can ultimately help improve patient care for people living with obesity at risk for CV events."

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

About semaglutide 2.4 mg
Semaglutide injection 2.4 mg is previously approved along with a reduced calorie diet and increased physical activity, for adults and children aged 12 years and older with obesity, or some adults with overweight who also have weight-related medical problems, to help them lose excess body weight and keep the weight off and to reduce the risk of major CV events such as death, heart attack, or stroke in adults with known heart disease and either obesity or overweight.²

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).²

Semaglutide is not approved in the U.S. to reduce heart failure outcomes, coronary revascularization, or all-cause death.²

About real-world evidence (RWE) SCORE study
Real-world studies are conducted to complement randomized controlled trials, which are the gold standard for evaluating the safety and efficacy of a treatment.³ The SCORE study analyzed MACE outcomes among semaglutide 2.4 mg users and non-users in real-world clinical practice.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.^1,2

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.⁴ In SELECT, established CVD was defined as a prior heart attack, prior stroke, or symptomatic PAD.⁴ The trial, initiated in 2018, enrolled 17,604 adults and was conducted in 41 countries at more than 800 investigator sites.⁴

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 U.S. headquarters in New Jersey and commercial, production, and research facilities in seven states plus Washington DC, Novo Nordisk employs approximately 8,000 people throughout the country. For more information, visit novonordisk-us.com, Facebook, Instagram, X, LinkedIn, and YouTube.

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References:

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.
Wegovy^® (semaglutide) injection 2.4 mg Prescribing Information. Plainsboro, NJ: Novo Nordisk Inc.; 2025.
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.
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.