Research summary

Semaglutide

Clinical — 10 studies

Semaglutide is a long-acting analogue of glucagon-like peptide-1 (GLP-1), a hormone released from the gut after eating. The research cited here is clinical: phase 3 trials and prespecified analyses in type 2 diabetes, obesity and cardiovascular disease.

Updated 29 September 2026

Being studied for

GLP-1 receptor pharmacology
Type 2 diabetes glycaemic trials
Obesity and overweight trials
Cardiovascular outcome trials
Heart failure subgroup analyses

What the research shows

Ten publications are cited, from 2017 to 2025, all from phase 3 clinical programmes. Three are trials in type 2 diabetes that measured glycaemic control and body weight: SUSTAIN 1 against placebo, SUSTAIN 2 against sitagliptin and SUSTAIN 7 against dulaglutide. Three are weight trials in adults with overweight or obesity: a 2021 trial in people without diabetes, STEP 2 in people with type 2 diabetes, and STEP 6 in east Asian adults with or without it. Four concern cardiovascular outcomes: a 2019 trial of oral semaglutide in type 2 diabetes, a 2023 trial in adults with established cardiovascular disease and overweight or obesity but no diabetes, a prespecified heart failure analysis of the SELECT trial, and prespecified analyses of the SOUL trial by SGLT2 inhibitor use.

Against placebo, SUSTAIN 1 reported lower HbA1c and body weight, with a safety profile similar to other GLP-1 receptor agonists. The 2021 trial reported a sustained reduction in body weight when semaglutide was given alongside lifestyle intervention; STEP 2 reported a larger fall in body weight than placebo in people with type 2 diabetes; and STEP 6 reported reductions in body weight and abdominal visceral fat area. In the 2019 oral trial, cardiovascular risk was not inferior to placebo. The 2023 trial reported fewer events of the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke than placebo over a mean follow-up of 39.8 months. The SELECT analysis reported fewer major cardiovascular and heart failure events in participants with and without clinical heart failure, and the SOUL analyses reported fewer major adverse cardiovascular events with oral semaglutide whether or not participants also took an SGLT2 inhibitor.

These results apply to the people and formulations studied. The 2023 trial admitted only people who already had cardiovascular disease, so its result cannot be generalised beyond that group. In the 2021 trial, lifestyle intervention was given in both arms, so its results describe semaglutide used alongside that programme rather than alone, and the preparation tested was the manufacturer's own. The SELECT and SOUL papers are prespecified subgroup analyses rather than primary results, and none of the cited evidence involves laboratory or animal work.

Published Research

Evidence profile

Human Phase 3 evidence

10 cited publications · 9 primary trials · 1 derived analysis

Findings below belong to the studies that reported them. They describe the material and conditions those authors used, not this product, and not an outcome to expect.

Core evidence

The publications most central to understanding this compound.

ClinicalPhase 3 randomised, double-blind, placebo-controlled cardiovascular outcomes trial

SELECT

Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes

Lincoff AM et al. · The New England journal of medicine · 2023

Population: Adults with overweight or obesity and established cardiovascular disease, without diabetes

A cardiovascular outcomes trial rather than a weight trial: the primary endpoint was a composite of death from cardiovascular causes, non-fatal myocardial infarction and non-fatal stroke.

As reported by the study

Route reported: Subcutaneous
Schedule: Once weekly under the trial protocol
Duration: Mean follow-up of approximately 40 months
Treatment arms: Semaglutide 2.4 mg · Placebo

Context: Enrolment required established cardiovascular disease, so the result does not describe a general population.

PMID 37952131DOI 10.1056/NEJMoa2307563NCT03574597View on PubMed

ClinicalPhase 3 randomised, double-blind, placebo-controlled trial

STEP 1

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Wilding JPH et al. · The New England journal of medicine · 2021

Population: Adults with overweight or obesity, without diabetes

The pivotal obesity trial for once-weekly semaglutide 2.4 mg, with percentage change in body weight over 68 weeks as a coprimary endpoint.

As reported by the study

Route reported: Subcutaneous
Schedule: Once weekly under the trial protocol
Duration: 68 weeks
Treatment arms: Semaglutide 2.4 mg · Placebo

Reported conclusion

“In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight.”

Context: Both arms received lifestyle intervention, so the result is not attributable to the drug alone. The material studied was the manufacturer's formulation.

PMID 33567185DOI 10.1056/NEJMoa2032183NCT03548935View on PubMed