Semaglutide 2.4 mg reduces burden of total cardiovascular events in people with established cardiovascular disease and overweight or obesity

  • Semaglutide 2.4 mg reduced total cardiovascular events by 22% in people with established cardiovascular disease (CVD) and overweight or obesity without diabetes.1
  • Obesity directly leads to cardiovascular morbidity, mortality and stroke with two in three obesity-related deaths linked to CVD.2,3
  • The analysis is based on SELECT, the first trial to demonstrate improvement in cardiovascular outcomes with an obesity medication.4

MISSISSAUGA, ON, March 31, 2025 /CNW/ - A new sub-analysis of the SELECT trial data shows semaglutide 2.4 mg substantially reduces the burden of total cardiovascular events in people with established CVD and overweight or obesity without diabetes, compared to placebo.1 Presented at the American College of Cardiology’s 74th Annual Scientific Session & Expo, these results add to the body of evidence from the SELECT cardiovascular outcomes trial, providing data on the benefits of semaglutide 2.4 mg beyond the first cardiovascular event.1

Professor Subodh Verma, Cardiac Surgeon at St. Michael’s Hospital and Canada Research Chair in Cardiovascular Surgery, who led the SELECT trial in Canada, stated: “SELECT represents a groundbreaking advancement for patients with heart disease who are living with overweight or obesity. The initial findings demonstrated a significant reduction in major adverse cardiovascular events, leading Health Canada to grant the first-ever indication for semaglutide 2.4 mg in individuals with established cardiovascular disease and a BMI ≥27 to reduce risk of non-fatal myocardial infarction. These new analyses, presented at the ACC meeting, confirm that semaglutide not only reduces the risk of a first heart attack or stroke but also significantly lowers the total burden of cardiovascular events—including subsequent heart attacks, strokes, and cardiovascular deaths. This underscores the robustness of this therapy as a foundational pillar in the treatment of heart disease.”

These findings are important as primary analyses of large cardiovascular outcome trials typically assess only the first event, whereas people living with obesity who are at high cardiovascular risk may experience multiple events over time, therefore the health burden of living with the disease and being at risk of injury and dying prematurely is not fully captured by these analyses.1,5

In this prespecified secondary analysis of the SELECT trial, semaglutide 2.4 mg reduced total events (first and subsequent) by 22% (MR 0.78; 95% CI 0.70–0.86; P<0.001),1 reduced non-fatal myocardial infarction (MI) by 31% (MR 0.69; 95% CI 0.58–0.82; P<0.001) and total coronary revascularizations by 26% (MR 0.74; 95% CI 0.65–0.84; P<0.001) compared to placebo, driving the overall reduction in total cardiovascular events.1

Among 17,604 participants followed for a mean of 39.8 months, 3,031 cardiovascular events occurred, with 1,947 (64%) as first events and 1,084 (36%) as subsequent events.1 Coronary revascularization represented 27.2% of first events and 72.9% of subsequent events, while non-fatal MI made up 26.2% of first events and 10.3% of subsequent events.1

Overall, this new SELECT sub-analysis shows that semaglutide 2.4 mg substantially reduces the first, subsequent, and total cardiovascular events in people with established CVD and overweight or obesity without diabetes.1

About obesity and cardiovascular disease

Over 8 million Canadian adults are living with obesity and many require support to effectively manage their condition.6 The prevalence of obesity, which increases the risk of serious chronic illness including heart disease, has grown over the last two decades.7,8 Canadians living with obesity are more than twice as likely to have heart disease than those with a healthy weight.9 Obesity is also associated with risk factors such as high blood pressure, chronic kidney disease and inflammation.10 Timely intervention for people with CVD and overweight or obesity is crucial to reduce residual risk for major adverse cardiovascular events (MACE), including heart attack or stroke.5 Despite therapeutic advances, there remains a significant unmet need for effective treatment options that can address the diseases associated with obesity.11

“Obesity Canada has been at the forefront of advancing disease understanding and evidence-based care to improve the lives of Canadians living with obesity. The sub-analysis of the SELECT trial data demonstrates an improvement in cardiovascular outcomes with obesity treatment,” said Dr. Sanjeev Sockalingam, Scientific Director of Obesity Canada. “Canadians living with obesity deserve evidence-based care to proactively manage their disease outlined in the Canadian Adult Obesity Clinical Practice Guideline, which includes the treatment pillars of psychological interventions, pharmacotherapy and surgery, which help support medical nutrition therapy, and physical activity.”

“Obesity has a profound impact on 8 million Canadians, with two-thirds experiencing obesity related risks associated with cardiovascular disease,” said Vince Lamanna, President of Novo Nordisk Canada Inc. “We are very pleased that semaglutide 2.4 mg has demonstrated significant impact in reducing the burden of cardiovascular events, offering hope for millions of Canadians living with obesity and cardiovascular disease.”

About the SELECT trial

SELECT was an international randomized, double-blind, parallel-group, placebo-controlled trial designed to evaluate the efficacy of semaglutide 2.4 mg versus placebo as an adjunct to standard of care for prevention of MACE in people with established CVD with overweight or obesity with no prior history of diabetes.12 People included in the trial were aged ≥45 years with a BMI ≥27 kg/m2 and were followed for a mean duration of 39.8 months.12

The primary objective of the SELECT trial was to demonstrate the superiority of semaglutide 2.4 mg compared to placebo with respect to reducing the incidence of three-point MACE consisting of cardiovascular death, non-fatal heart attack (myocardial infarction) or non-fatal stroke.4 Key secondary objectives were to compare the effects of semaglutide 2.4 mg to placebo with regards to mortality, heart failure, cardiovascular risk factors including glucose metabolism, body weight and kidney function.4

The trial, initiated in 2018, enrolled 17,604 adults and was conducted in 41 countries at more than 800 investigator sites.

The SELECT primary data was first presented at the American Heart Association Congress in November 2023 and simultaneously published in the New England Journal of Medicine.4 The trial has up to now provided various data sets and sub-analyses, presented at scientific congresses across the spectrum of cardiovascular, kidney and metabolic diseases, as well as publications in well-known scientific journals.4,13-19

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 Lincoff, MA, Colhoun HM, Emerson S. (2025) Effect of the GLP-1 receptor agonist semaglutide on total cardiovascular events in patients with cardiovascular disease and overweight or obesity but no diabetes in the SELECT trial. Presented at ACC 2025, Chicago, United States.

2 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.

3 Martin-Timon I, Sevillano-Collantes C, Segura-Galindo A, et al. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World J Diabetes. 2014; 5:444-470.

4 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.

5 Koskinas KC, Van Craenenbroeck EM, Antoniades C et al. Obesity and cardiovascular disease: an ESC clinical consensus statement. European Heart Journal. 2024;45(38):4063–4098.

6 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

7 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

8 Twells LK, Janssen I, Kuk JL. Canadian Adult Obesity Clinical Practice Guidelines: Epidemiology of Adult Obesity. https://obesitycanada.ca/guidelines/epidemiology

9 Heart and Stroke Foundation. Healthy weight and waist. https://www.heartandstroke.ca/healthy-living/healthy-weight/healthy-weight-and-waist

10 Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2021;143:e984-e1010.

11 Rigopoulos AG, Bakogiannis C, de Vecchis R, et al. Acute heart failure: An unmet medical need. Herz. 2019; 44:53-55.

12 Lingvay I, Brown-Frandsen K, Colhoun HM, et al. Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics. Obesity (Silver Spring). 2023; 31:111-122.

13 Deanfield JE, Verma S, Scirica BM, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. Lancet. 2024;404(10458).

14. Ryan DH, Lingvay I, Deanfield JE, et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med. 2024;30:2049–2057.

15. Scirica BM, Lincoff AM, Lingvay I, et al. The effect of semaglutide on mortality and COVID-19–related deaths: an analysis from the SELECT trial. J Am Coll Cardiol. 2024;84(10):1350–1359.

16. Kahn SE, Deanfield JE, Jeppesen OK, et al. Effect of semaglutide on regression and progression of glycemia in people with overweight or obesity but without diabetes in the SELECT trial. Diabetes Care. 2024;47(8):1350–1359.

17. Kosiborod MN, Deanfield JE, Pratley RE, et al. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet. 2024;404(10456):949-961.

18. Colhoun HM, Lingvay I, Brown PM, et al. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nat Med. 2024;30:2058–2066.

19. Nicholls SJ, Ryan DH, Deanfield JE, et al. Semaglutide reduces hospital admissions in patients with obesity or overweight and established CVD. Presented at ObesityWeek® 2024, San Antonio, USA, November 3, 2024.

SOURCE Novo Nordisk Canada Inc.

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