Effect of once-weekly subcutaneous semaglutide on arterial inflammation in people with type 2 diabetes and cardiovascular disease using PET-MRI: Primary results of a randomized, double-blind, placebo-controlled trial.

James S, Christoffersen AD, David JP, Hacker M, Jensen MDRJ, Mellbin L, Pieber TR, Ripa RS, Rossing P, Svehlikova E, Kjaer A

American heart journal7 May 2025Cited by 5 (Europe PMC)

PMID40345413DOI10.1016/j.ahj.2025.05.001PepBankPUB-40345413

Publisher page PubMedAsk about this study

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Summary

BackgroundSemaglutide has demonstrated cardiovascular benefits in people with type 2 diabetes (T2D) with cardiovascular disease (CVD). Inflammation plays a well-documented role in atherosclerosis and glucagon-like peptide-1 receptor agonists, like semaglutide, have shown anti-inflammatory effects in animal and clinical studies. This trial investigated the effect of semaglutide on atherosclerotic inflammation in the carotid arteries using positron emission tomography (PET)-magnetic resonance imaging (MRI).MethodsPatients with T2D and CVD were randomized to double-blinded once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary and key secondary endpoints used PET-MRI with [¹⁸F]FDG and [⁶⁸Ga]DOTATATE tracers to assess change from baseline to week 26 in plaque inflammation in the segments of the carotid arteries that were determined to be the most diseased and where plaque inflammation was quantified by the maximum target-to-background ratio (TBR_max) of the tracers. Additional secondary endpoints assessed plaque morphology and burden using MRI at week 52, including total wall volume, lipid-rich necrotic core volume, and fibrous cap thickness.ResultsOf 101 patients, 87.1% were male, mean age was 66 years and they were well-treated according to guidelines. No significant treatment differences were observed between semaglutide and placebo for change in plaque inflammation at week 26 with either tracer; TBR_max of FDG (estimated treatment difference [ETD]: 0.033, 95% confidence interval [CI]: -0.118;0.184) and [⁶⁸Ga]DOTATATE (ETD: 0.045, 95% CI: -0.314;0.404).ConclusionsThis trial explored the feasibility of following plaque inflammation with PET-MRI using [¹⁸F]FDG and [⁶⁸Ga]DOTATATE. A significant effect of semaglutide versus placebo on carotid plaque inflammation could not be detected through the methodology used in this trial, likely due to minimal baseline inflammation. However, this does not exclude an effect of semaglutide on inflammation seen in previous preclinical and clinical studies.Trial registrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT04032197.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. 2 results from people.

01HumanRandomized controlled trialEfficacy outcome
In people with type 2 diabetes and cardiovascular disease, semaglutide did not change carotid plaque inflammation measured by FDG TBRmax at week 26 compared with placebo.
In plain wordsIn people with type 2 diabetes and heart disease, semaglutide did not change artery plaque inflammation seen on FDG scans more than placebo did.
Peptide
Semaglutide
Outcome
No significant changeChange in carotid plaque inflammation at week 26 (FDG TBRmax)
Study
n = 101
Comparator
Placebo
Outcome group
Inflammation markers · Cardiovascular
Studied dose
1.0 mg · subcutaneous · 26 weeksAs given in this study (human).
Measurements
Estimated treatment difference
0.033 TBRmax
FDG
Source sentences
Summary
No significant treatment differences were observed between semaglutide and placebo for change in plaque inflammation at week 26 with either tracer; TBR_max of FDG (estimated treatment difference [ETD]: 0.033, 95% confidence interval [CI]: -0.118;0.184) and [⁶⁸Ga]DOTATATE (ETD: 0.045, 95% CI: -0.314;0.404).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with T2D and CVD were randomized to double-blinded once-weekly subcutaneous semaglutide 1.0 mg or placebo.
Show in the study text Report a problemFND-4034541301
02HumanRandomized controlled trialEfficacy outcome
In people with type 2 diabetes and cardiovascular disease, semaglutide did not change carotid plaque inflammation measured by [68Ga]DOTATATE TBRmax at week 26 compared with placebo.
In plain wordsIn people with type 2 diabetes and heart disease, semaglutide did not change artery plaque inflammation seen on DOTATATE scans more than placebo did.
Peptide
Semaglutide
Outcome
No significant changeChange in carotid plaque inflammation at week 26 ([68Ga]DOTATATE TBRmax)
Study
n = 101
Comparator
Placebo
Outcome group
Inflammation markers · Cardiovascular
Studied dose
1.0 mg · subcutaneous · 26 weeksAs given in this study (human).
Measurements
Estimated treatment difference
0.045 TBRmax
DOTATATE
Source sentences
Summary
No significant treatment differences were observed between semaglutide and placebo for change in plaque inflammation at week 26 with either tracer; TBR_max of FDG (estimated treatment difference [ETD]: 0.033, 95% confidence interval [CI]: -0.118;0.184) and [⁶⁸Ga]DOTATATE (ETD: 0.045, 95% CI: -0.314;0.404).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with T2D and CVD were randomized to double-blinded once-weekly subcutaneous semaglutide 1.0 mg or placebo.
Show in the study text Report a problemFND-4034541302

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 1NCT04032197

A Research Study of How Semaglutide Works in People With Disease Affecting the Heart and/or Blood Vessels and Type 2 Diabetes

Novo Nordisk A/Sn = 10112 Aug 2019 to 6 Jun 2023

Diabetes Mellitus, Type 2

Trial page ClinicalTrials.govUpdated 29 Apr 2025

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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