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# Wegovy Cuts Major Cardiovascular Events 20% in 17,604-Patient SELECT Trial
- URL: https://www.theamericanquorum.com/taq-historical-2023-08-12-healthcare/
- Published: 2023-08-13T03:59:00.000Z
- Updated: 2023-08-13T03:59:00.000Z
- Description: Novo Nordisk says semaglutide 2.4 mg reduced major cardiovascular events by 20% in the 17,604-patient SELECT trial of adults with overweight or obesity, established cardiovascular disease and no diabetes.
- Author: Kenneth R. Deans Jr.
- Tags: Healthcare, #Import 2026-09-01 04:54

Semaglutide 2.4 mg, sold as Wegovy for chronic weight management, reduced the risk of major adverse cardiovascular events by 20% in a 17,604-patient trial of adults with overweight or obesity and established cardiovascular disease but no history of diabetes, Novo Nordisk announced Tuesday. The [top-line SELECT results](https://www.globenewswire.com/news-release/2023/08/08/2720343/0/en/novo-nordisk-a-s-semaglutide-2-4-mg-reduces-the-risk-of-major-adverse-cardiovascular-events-by-20-in-adults-with-overweight-or-obesity-in-the-select-trial.html?ref=theamericanquorum.com) are the first evidence from a large outcomes trial that a medicine approved for weight management can reduce a composite of cardiovascular death, nonfatal heart attack and nonfatal stroke in this population.

The result is important because the trial was designed around cardiovascular events rather than weight loss alone. Participants were at least 45 years old, had a body-mass index of 27 or higher and had established cardiovascular disease. The study excluded people with a prior history of diabetes, creating a direct test of whether semaglutide can reduce cardiovascular risk beyond its established role in glucose management.

## SELECT was built to answer a question obesity trials had not settled

The [registered SELECT protocol](https://clinicaltrials.gov/study/NCT03574597?ref=theamericanquorum.com) describes a randomized, double-blind, placebo-controlled outcomes trial conducted internationally. Participants received semaglutide 2.4 mg once weekly or placebo, both added to standard care, and were followed for as long as five years. The trial was event driven, with the primary endpoint defined as the first occurrence of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke.

That design reflects a long-standing gap in obesity treatment. Weight reduction can improve blood pressure, glycemic measures and other cardiovascular risk factors, but a large trial still had to demonstrate that a weight-management medicine could translate those intermediate changes into fewer major clinical events. The 2020 [SELECT rationale and design paper](https://utsouthwestern.elsevierpure.com/en/publications/semaglutide-effects-on-cardiovascular-outcomes-in-people-with-ove/?ref=theamericanquorum.com) explicitly framed the study around that question, calling it the first cardiovascular outcomes trial designed to test superiority for an anti-obesity medication in people with established cardiovascular disease and overweight or obesity without diabetes.

Novo Nordisk said 1,270 first major cardiovascular events accumulated during the study and that all three components of the composite endpoint contributed to the reported 20% reduction. The company has not yet released the full event-by-event dataset, hazard ratios, subgroup analyses or detailed safety tables. Those data are expected to be presented at a scientific meeting later this year.

## The finding extends an already substantial semaglutide evidence base

Semaglutide is a glucagon-like peptide-1 receptor agonist, or GLP-1 drug. The class was developed for diabetes, but semaglutide at a 2.4-mg weekly dose demonstrated substantial weight loss in the STEP program. In the 2021 [STEP 1 trial](https://www.nejm.org/doi/full/10.1056/NEJMoa2032183?ref=theamericanquorum.com), adults with overweight or obesity without diabetes lost an average 14.9% of body weight with semaglutide plus lifestyle intervention, compared with 2.4% with placebo plus lifestyle intervention.

Cardiovascular benefit has also been seen with lower-dose semaglutide in people with type 2 diabetes. The earlier [SUSTAIN-6 trial](https://www.nejm.org/doi/full/10.1056/NEJMoa1607141?ref=theamericanquorum.com) found fewer major cardiovascular events with semaglutide than placebo among high-risk patients with diabetes. SELECT tests a different and broader clinical proposition: whether the drug can reduce events in people whose cardiovascular disease and excess weight place them at high risk even without diabetes.

The American College of Cardiology’s Aug. 10 [summary of the announcement](https://www.acc.org/Latest-in-Cardiology/Articles/2023/08/10/14/29/SELECT-Semaglutide-Reduces-Risk-of-MACE-in-Adults-With-Overweight-or-Obesity?ref=theamericanquorum.com) highlights the trial’s 41-country scale and notes that all three primary-event components moved in a favorable direction. The size of the study gives the result more weight than a metabolic or weight-loss endpoint alone because it is based on clinical events that directly affect survival and disability.

## Top-line data are consequential, but important details remain unknown

The announcement is not the same as a peer-reviewed publication. Novo Nordisk said the safety and tolerability profile appeared consistent with previous semaglutide 2.4-mg trials, but clinicians do not yet have the complete adverse-event data needed to weigh the cardiovascular benefit against treatment discontinuations, gastrointestinal effects or rarer risks.

The existing Wegovy indication is for chronic weight management, not cardiovascular risk reduction. FDA materials from the drug’s original approval period describe semaglutide 2.4 mg as an adjunct to reduced-calorie diet and increased physical activity for adults with obesity or overweight plus a weight-related condition. A June 2021 [FDA update](https://www.fda.gov/consumers/june-2021-office-womens-health-e-update?ref=theamericanquorum.com) summarized the original approval and the population eligible for treatment. Novo Nordisk now says it intends to seek expanded U.S. and European labeling based on SELECT.

That regulatory step will require the agencies to evaluate the full trial dataset, not only the 20% relative reduction in the primary endpoint. Absolute event rates, treatment exposure, discontinuation, adverse events and the consistency of benefit across patient groups will all shape how broadly the result can be applied.

## The trial may change how obesity treatment is evaluated

The immediate clinical significance is that obesity pharmacotherapy now has an outcomes result tied to heart attack, stroke and cardiovascular death rather than weight change alone. For patients who already have cardiovascular disease, that distinction is substantial. It also affects how physicians, insurers and health systems may evaluate the medical value of expensive long-term weight-management treatment.

At the same time, SELECT does not establish cardiovascular benefit for everyone with obesity. Its participants already had cardiovascular disease, were at least 45 years old and did not have diabetes. The result therefore supports a secondary-prevention population, and broader conclusions will require other evidence.

Still, the scale and direction of the finding make SELECT one of the most consequential obesity-drug studies to date. Novo Nordisk’s announcement moves the discussion from whether semaglutide produces large weight loss—already demonstrated—to whether treating obesity pharmacologically can prevent major cardiovascular events. The top-line answer from 17,604 participants is yes, with a reported 20% relative reduction. The next test will be whether the detailed data and regulatory review support an expanded cardiovascular indication.