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LITERATURE REVIEW · CARDIOVASCULAR OUTCOMES TRIAL

SELECT trial

Semaglutide and cardiovascular outcomes in obesity without diabetes — Lincoff et al., New England Journal of Medicine, 2023.

QUICK ANSWER
TL;DR

Quick answer

SELECT was a 17,604-patient randomised double-blind trial of once-weekly subcutaneous Semaglutide 2.4 mg versus placebo in adults with overweight/obesity and established cardiovascular disease, without diabetes. The three-point MACE composite was reduced by 20% with Semaglutide over a mean 39.8 months.
EXTENDED ANSWER
AI-ready

Extended answer

What was the SELECT trial?

SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) was a randomised, double-blind, placebo-controlled cardiovascular outcomes trial evaluating once-weekly subcutaneous Semaglutide 2.4 mg in adults with overweight or obesity (BMI ≥ 27) and established cardiovascular disease but without diabetes. Published in the New England Journal of Medicine in 2023 (Lincoff et al.), SELECT enrolled 17,604 participants and followed them for a mean of 39.8 months. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (three-point MACE), and Semaglutide reduced the primary composite by 20% versus placebo. SELECT is the first large randomised trial to demonstrate cardiovascular benefit of a GLP-1 receptor agonist in the obesity- without-diabetes population and shaped subsequent guideline discussions. Oxford Research Peptides describes SELECT for educational purposes only.
KEY FACTS

Key facts

Compound
Semaglutide 2.4 mg SC weekly
Design
Randomised, double-blind, placebo-controlled
Population
17,604 adults with overweight/obesity + established CVD, no T2D
Follow-up (mean)
39.8 months
Primary outcome
3-point MACE (CV death, non-fatal MI, non-fatal stroke)
Journal
New England Journal of Medicine (2023)
PMID
37952131
DOI
10.1056/NEJMoa2307563

Background

Prior GLP-1 receptor agonist cardiovascular outcomes trials enrolled adults with type 2 diabetes. SELECT was designed to evaluate cardiovascular outcomes in a specifically non-diabetic obesity population with established cardiovascular disease.[4]

Study design

Randomised 1:1 to Semaglutide 2.4 mg weekly or matching placebo. All participants received standard-of-care cardiovascular management. Event-driven design.

Population

17,604 adults aged ≥ 45 years, BMI ≥ 27, established cardiovascular disease (prior MI, prior stroke, or symptomatic peripheral artery disease), and without type 2 diabetes.

Primary outcomes

Three-point MACE (cardiovascular death, non-fatal MI, non-fatal stroke). Semaglutide reduced the primary composite by 20% versus placebo. Weight change and other secondary outcomes were reported alongside the primary.[4]

Scientific significance

  • First large RCT demonstrating cardiovascular benefit of a GLP-1 receptor agonist in obesity without diabetes.
  • Extends the cardiovascular relevance of the class beyond the diabetes population.
  • Reframed regulatory and guideline discussions around Semaglutide's role in cardiovascular prevention.

Limitations

Research limitations

  • SELECT enrolled adults with established cardiovascular disease; extrapolation to primary prevention is not direct.
  • Approximately 3/4 of enrolled participants were male — limiting generalisability across sex.
  • Weight change data are secondary; SELECT was not a weight-management trial by primary design.
  • Long-term (> 5 year) durability of effect requires ongoing follow-up.

Research-use framing

Educational literature summary only. Not clinical guidance.

Related reading: Semaglutide monograph, Semaglutide research applications, SUSTAIN-6 and STEP programme.

References5

  1. 1.

    Marso SP, Bain SC, Consoli A, et al.. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6).. New England Journal of Medicine. 2016;375(19):1834-1844.

    DOI: 10.1056/NEJMoa1607141PMID: 27633186
  2. 2.

    Wilding JPH, Batterham RL, Calanna S, et al.. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).. New England Journal of Medicine. 2021;384(11):989-1002.

    DOI: 10.1056/NEJMoa2032183PMID: 33567185
  3. 3.

    Davies M, Færch L, Jeppesen OK, et al.. Semaglutide 2·4 mg once a week in adults with overweight or obesity and type 2 diabetes (STEP 2).. Lancet. 2021;397(10278):971-984.

    DOI: 10.1016/S0140-6736(21)00213-0PMID: 33667417
  4. 4.

    Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).. New England Journal of Medicine. 2023;389(24):2221-2232.

    DOI: 10.1056/NEJMoa2307563PMID: 37952131
  5. 5.

    Perkovic V, Tuttle KR, Rossing P, et al.. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes (FLOW).. New England Journal of Medicine. 2024;391(2):109-121.

    DOI: 10.1056/NEJMoa2403347PMID: 38785209
EVIDENCE SUMMARY
Evidence

Evidence summary

Strong evidence
Research confidenceHigh confidence
Landmark cardiovascular outcomes trial (Lincoff et al., NEJM 2023). Widely cited across cardiovascular and metabolic literature.
RELATED GUIDES
COMPOUND REFERENCE
EDITORIAL NOTICE

Research use only

All materials referenced are supplied strictly for in-vitro laboratory research. Not for human or animal consumption, diagnosis, or therapeutic use.
VERSION HISTORY
Editorial Team
Oxford Research Peptides Editorial Team
In-house editorial staff
Oxford Research Peptides
Scientific Reviewer
Scientific Review Panel
Independent scientific review
Oxford Research Peptides

Publication information

Published
2026-10-15
Updated
2026-10-15
Reviewed
2026-10-15
Version
1.0

Revision history

  1. v1.02026-10-15· Editorial Team

    Authority Sprint 2D — initial publication of GLP-1 foundation study summaries.

Editorial standards

Content is reviewed against our editorial process for scientific accuracy, sourcing, and clarity. Read our editorial standards.

Conflict of interest

Oxford Research Peptides supplies research-grade reference peptides commercially. Editorial pages are drafted and reviewed to describe published scientific literature accurately and do not recommend, promote or endorse any specific commercial product. Product mentions on educational pages are strictly for cross-referencing catalogue entries.

Next scheduled review: 2028-04-15. Our research methodology describes how the review is conducted.

Research use only

All materials referenced are supplied strictly for in-vitro laboratory research. Not for human or animal consumption, diagnosis, or therapeutic use.
Published: 2026-10-15Updated: 2026-10-15