Drug

Semaglutide

Peer-reviewed research on semaglutide across obesity, type 2 diabetes, and cardiovascular outcome trials.

Sources: FDA label · 10 registered trials · 5 key papers

Semaglutide at a glance

GLP-1 Receptor Agonists

Mechanism: glucagon-like peptide 1 (GLP-1) receptor agonist · FDA label (DailyMed)

Boxed warning:Risk of thyroid C-cell tumors

FDA-approved indications (Ozempic)

As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
To reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease.
To reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with type 2 diabetes mellitus and chronic kidney disease.

Source: , label dated Jul 30, 2026

FDA-approved indications (Wegovy)

In combination with a reduced calorie diet and increased physical activity to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight.
In combination with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 12 years and older with obesity.
In combination with a reduced calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in adults with overweight in the presence of at least one weight-related comorbid condition.

Source: Wegovy label (DailyMed), label dated Apr 23, 2024

Overview

Unverified · drafted by AI from the sources cited below

Definition

Semaglutide is a glucagon-like peptide and GLP-1 agonist that is utilized for obesity management and to enhance glycemic control in patients with type 2 diabetes mellitus.1 It acts as a glucagon-like peptide-1 receptor agonist.2

Treatment

It improves symptoms and physical limitations in patients with obesity-related heart failure with preserved ejection fraction who have a body mass index of at least 30 kg/m².2 An interim analysis at week 72 demonstrated that resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group.3 Additionally, it has been compared retrospectively over 12 months with tirzepatide for achieving treatment targets in type 2 diabetes.4

Open questions

Anecdotal reports have raised the possibility that semaglutide may be associated with an increased risk of nonarteritic anterior ischemic optic neuropathy, which has prompted retrospective cohort investigations.1 Furthermore, ongoing phase 3 trials are evaluating the potential disease-modifying, neuroprotective effects of semaglutide in men and women aged 55-85 years with early-stage symptomatic Alzheimer's disease.2

Landmark trials

Primary results of 4 trials behind the evidence on semaglutide, as each trial’s own publication reports them.

Left of the line at 1 favours the intervention; square size tracks trial size.Favours the interventionNo significant differenceFavours the comparator

0.512

FLOW
semaglutide vs placebo · 3,533 patients · N Engl J Med 2024
In patients with type 2 diabetes and chronic kidney disease
Primary outcome: major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of <15 ml per minute per 1.73 m2), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes
HR 0.76 (0.66–0.88)
SELECT
semaglutide vs placebo · 17,604 patients · N Engl J Med 2023
In patients with preexisting cardiovascular disease and overweight or obesity but without diabetes
Primary outcome: a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis
HR 0.80 (0.72–0.90)
SUSTAIN-6
semaglutide vs placebo · 3,297 patients · N Engl J Med 2016
In patients with type 2 diabetes who were on a standard-care regimen
Primary outcome: the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke
HR 0.74 (0.58–0.95)

Reported as a difference or win ratio

STEP-HFpEFdual primary end point 1: KCCQ-CSS change
semaglutide vs placebo · 529 patients · N Engl J Med 2023
Primary outcome: the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS
“estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P<0.001”
STEP-HFpEFdual primary end point 2: % body-weight change
semaglutide vs placebo · 529 patients · N Engl J Med 2023
Primary outcome: the change in body weight
“estimated difference, -10.7 percentage points; 95% CI, -11.9 to -9.4; P<0.001”

Results are quoted from each trial’s primary publication abstract (PubMed); the trial name links to the paper. Ratios below 1 favour the intervention.

Trials by indication

Registered trials with semaglutide in an arm, past phase 1 with at least 50 participants: the largest in each indication, newest first. Trials that give it only as the comparator are tagged; trials that give it in every arm are listed last.

Type 2 diabetes

REMODEL
A Research Study to Find Out How Semaglutide Works in the Kidneys Compared to Placebo, in People With Type 2 Diabetes and Chronic Kidney Disease (the REMODEL Trial)
NCT04865770 · Phase 3 · Completed · 106 participants · started 2021
Effects of Semaglutide on Functional Capacity in Patients With Type 2 Diabetes and Peripheral Arterial Disease
NCT04560998 · Phase 3 · Completed · 792 participants · started 2020
FLOW
A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease
NCT03819153 · Phase 3 · Completed · 3,533 participants · started 2019
SUSTAIN™ 6
Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes
NCT01720446 · Phase 3 · Completed · 3,297 participants · started 2013

Obesity

STEP-HFpEF
Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity
NCT04788511 · Phase 3 · Completed · 529 participants · started 2021
SELECT
Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity
NCT03574597 · Phase 3 · Completed · 17,604 participants · started 2018

Heart failure

A Prospective, Randomized, Open-Label, Blinded-Endpoint, Parallel-Group, Phase IIb Proof-of-Concept Clinical Trial of Semaglutide Added to Dapagliflozin Versus Dapagliflozin Monotherapy in Patients With Heart Failure and Previous Surgical Prosthetic Valve Replacement
NCT07610174 · Phase 2 · Completed · 160 participants · started 2025
CAMEO-SEMA
Evaluation of the Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction (CAMEO-SEMA)
NCT05371496 · Phase 4 · Completed · 81 participants · started 2022

Stroke

A Multicentre, Prospective, Randomized, Open-label, Blinded Endpoint, Clinical Trial Evaluating Subcutaneous Semaglutide in Patients With Acute Ischaemic Stroke Due to Anterior Circulation Large Vessel Occlusion Treated With Endovascular Thrombectomy
NCT07511543 · Phase 3 · Not yet recruiting · 826 participants · started 2026

Given as background therapy

The Cardiovascular Safety and Efficacy of Cagrilintide s.c. in Combination With Semaglutide s.c. (CagriSema s.c.) in Participants With Established Cardiovascular DiseaseBackground in every arm
NCT05669755 · Phase 3 · Active not recruiting · 7,101 participants · started 2023

Source: ClinicalTrials.gov registry records.

How this page is built

A clinical question appears here only when its condition matches this topic, an outcome and a comparator were extracted from the studies, at least two studies and a patient count are on file, and the certainty is low or higher.

Supports benefit, no benefit shown, and mixed describe the direction of the measured effect. No benefit shown means the evidence does not support a benefit. It is not a finding of harm. Too little evidence means the question did not clear that bar.

Study count, RCT count, and patient count are separate. The patient total adds only studies that are linked into a study family and whose sample size is not flagged as implausible. A reversal is listed only when at least one randomized trial sits on each side of the change.

The overview is drafted from the guideline recommendations, trials, papers, and questions on this page, and every sentence has to cite one of them. It stays unverified until an NPI-verified clinician or a Synapse admin approves it. Approving records that person's name.

Semaglutide

Semaglutide at a glance

Overview

Definition

Treatment

Open questions

Landmark trials

Reported as a difference or win ratio

Trials by indication

Safety and label changes

Other GLP-1 Receptor Agonists

Key papers

New research on Semaglutide

How this page is built

Leading authors