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Study · Randomized controlled trial · 2026

6 results

Effect of Semaglutide on the Inflammatory Biomarker High-Sensitivity CRP in Patients With Established Cardiovascular Disease and Overweight or Obesity in SELECT: A Prespecified Secondary Analysis.

Plutzky J, Bogdański P, Colhoun HM, Dağdelen S, Deanfield JE, Emerson SS, Hovingh GK, Kahn SE, Ekström K, Latkovskis G, Lehrke M, Hardt-Lindberg S and 8 more

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Lingvay I, Nicholls SJ, Kalayci Oral T, Terns PP, Rasmussen S, Ridker PM, Ryan DH, Lincoff AM

Circulation18 Aug 2026

PMID42610271 (opens in a new tab)PMCIDPMC13574348 (opens in a new tab)DOI10.1161/circulationaha.125.074482 (opens in a new tab)PepBankPUB-42610271
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Summary

BackgroundIn SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity), among 17 604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes, randomization to the glucagon-like peptide-1 receptor agonist semaglutide significantly reduced the primary outcome of major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) compared with placebo (mean follow-up, 39.8 months). Inflammation, as indicated by plasma hsCRP (high-sensitivity C-reactive protein) level, is implicated as a biomarker predicting cardiovascular risk in obesity and atherosclerotic cardiovascular disease. SELECT provides a unique opportunity to study the relationship among hsCRP, obesity, weight loss, and MACE outcomes in semaglutide versus placebo groups.MethodsIn this prespecified SELECT substudy, we evaluated whether baseline hsCRP levels predicted MACE risk and examined the relationships between changes in hsCRP levels and time to first MACE, baseline body weight, weight loss, and other clinical measures among treatment groups over time (104, 208 weeks) using multiple approaches, including Cox modeling.ResultsBaseline hsCRP level, which was similar in the semaglutide (geometric mean 1.96 mg/L) and placebo (geometric mean 1.91 mg/L) groups, was prognostic of future MACE. The risk of MACE increased across baseline hsCRP level <2, 2-<10, and ≥10 mg/L subgroups, including significant associations with cardiovascular and all-cause death. Semaglutide reduced hsCRP levels (-37.8% [104 weeks]) and risk of MACE across all hsCRP subgroups. Greater reductions in ratio-to-baseline hsCRP with semaglutide were associated with greater weight loss, but preceded major weight loss, evident by 4 and 8 weeks, and occurred among those without weight loss. Semaglutide-associated changes in hsCRP were independent of low-density lipoprotein cholesterol levels, statin use, and atherosclerotic cardiovascular disease entry criteria. hsCRP reductions were found to be prognostic of decreased risk of MACE. Modeling suggests decreased inflammation as contributing in part to the benefits seen with semaglutide in SELECT.ConclusionsIn SELECT, hsCRP data at baseline and in response to treatment with semaglutide support inflammation as a potential prognostic factor associated with cardiovascular risk in these generally well-treated patients with atherosclerotic cardiovascular disease and overweight or obesity but not diabetes. These findings suggest that the MACE reduction observed with semaglutide versus placebo in SELECT may have partially involved a decrease in inflammation.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03574597.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In adults with atherosclerotic cardiovascular disease and overweight or obesity without diabetes, semaglutide reduced hsCRP levels at 104 weeks versus placebo.

    In plain wordsIn adults with heart disease and overweight or obesity, semaglutide lowered the inflammation marker hsCRP more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreasehsCRP change at 104 weeks
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Measurements

    hsCRP change
    −37.8%
    104 weeks

    Source sentences

    Summary
    Semaglutide reduced hsCRP levels (-37.8% [104 weeks])
    1 context sentence
    Summary · context
    among 17 604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes
  2. 02HumanRandomized controlled trialEfficacy outcome

    In adults with atherosclerotic cardiovascular disease and overweight or obesity without diabetes, semaglutide reduced MACE risk across all baseline hsCRP subgroups versus placebo.

    In plain wordsIn adults with heart disease and overweight or obesity, semaglutide lowered the risk of major heart events at every starting hsCRP level, compared with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseMACE risk across hsCRP subgroups
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    and risk of MACE across all hsCRP subgroups.
    1 context sentence
    Summary · context
    among 17 604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes
  3. 03HumanRandomized controlled trialMechanism

    In semaglutide-treated adults in SELECT, greater hsCRP reductions were associated with greater weight loss.

    In plain wordsIn adults taking semaglutide, bigger drops in the inflammation marker hsCRP were linked to more weight loss.

    Peptide
    Semaglutide
    Outcome
    Not applicableAssociation of hsCRP reduction with weight loss
    Study

    n: not reported in source

    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Greater reductions in ratio-to-baseline hsCRP with semaglutide were associated with greater weight loss
    1 context sentence
    Summary · context
    among 17 604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes
  4. 04HumanRandomized controlled trialMechanism

    In semaglutide-treated adults in SELECT, hsCRP reductions preceded major weight loss and occurred among those without weight loss.

    In plain wordsIn adults taking semaglutide, the inflammation marker hsCRP fell before major weight loss and also in people who did not lose weight.

    Peptide
    Semaglutide
    Outcome
    DecreaseTiming of hsCRP reduction relative to weight loss
    Study

    n: not reported in source

    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    but preceded major weight loss, evident by 4 and 8 weeks, and occurred among those without weight loss.
    1 context sentence
    Summary · context
    among 17 604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes
  5. 05HumanRandomized controlled trialMechanism

    In adults in SELECT, semaglutide-associated changes in hsCRP were independent of LDL cholesterol levels, statin use and atherosclerotic cardiovascular disease entry criteria.

    In plain wordsIn adults taking semaglutide, the drop in hsCRP did not depend on LDL cholesterol levels or statin use.

    Peptide
    Semaglutide
    Outcome
    No significant changeIndependence of hsCRP change from LDL cholesterol, statin use and entry criteria
    Study

    n: not reported in source

    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Semaglutide-associated changes in hsCRP were independent of low-density lipoprotein cholesterol levels, statin use, and atherosclerotic cardiovascular disease entry criteria
    1 context sentence
    Summary · context
    among 17 604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes
  6. 06HumanRandomized controlled trialMechanism

    In adults in SELECT, hsCRP reductions were prognostic of decreased MACE risk.

    In plain wordsIn adults in this trial, a bigger drop in the inflammation marker hsCRP was linked to a lower risk of major heart events.

    Peptide
    Semaglutide
    Outcome
    DecreasePrognostic value of hsCRP reduction for MACE
    Study

    n: not reported in source

    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    hsCRP reductions were found to be prognostic of decreased risk of MACE.
    1 context sentence
    Summary · context
    among 17 604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes

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 · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT03574597

Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity

Novo Nordisk A/Sn = 17,60424 Oct 2018 to 29 Jun 2023

Overweight · Obesity

Trial pageClinicalTrials.govUpdated 30 Aug 2024

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.

  1. Version 2Current

    11 Oct 2026, 00:04 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:06 UTC

    First added · source update from Europe PMC

Subjects

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