Semaglutide on liver fibrosis and heart outcomes in patients at high risk of liver fibrosis: a prespecified analysis of the SELECT randomized trial.

Meyhöfer SM, Cariou B, Cercato C, Colhoun HM, Deanfield J, Long MT, Jeppesen OK, Lincoff AM, Lingvay I, Plutzky J, Newsome PN, Nicholls SJ and 4 more

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Quiroga M, Santini F, Sanyal AJ, Kahn SE

Nature medicine2 Apr 2026Cited by 4 (Europe PMC)

PMID41928037PMCIDPMC13190271DOI10.1038/s41591-026-04281-1PepBankPUB-41928037

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Summary

In the SELECT trial, once-weekly subcutaneous semaglutide reduced major adverse cardiovascular events (MACE) by 20% versus placebo in patients with atherosclerotic cardiovascular disease and obesity but without diabetes. We examined semaglutide in SELECT patients at high risk for substantial liver fibrosis in a prespecified secondary analysis. Liver biochemical tests and steatosis risk according to fatty liver index were assessed over 104 weeks. Subgroup analyses of the primary MACE (a composite endpoint including cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) outcome used baseline Fibrosis-4 scores ≥ 1.3, age-specific (≥1.3 ( 2.67. MACE was reduced by 26% (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63-0.88; P = 0.0004), 21% (HR 0.79; 95% CI 0.63-0.98; P = 0.035) and 34% (HR 0.66; 95% CI 0.39-1.10; P = 0.11), respectively. Semaglutide led to a 28% greater decrease in fatty liver index versus placebo (HR 0.72; 95% CI 0.71-0.73; P < 0.0001). In conclusion, semaglutide reduced MACE versus placebo in patients at risk for substantial liver fibrosis, as seen in the overall SELECT population. ClinicalTrials.gov registration no. NCT03574597.

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

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

01HumanRandomized controlled trialEfficacy outcome
In patients with atherosclerotic cardiovascular disease and obesity at high risk of liver fibrosis (Fibrosis-4 of 1.3 or more), semaglutide reduced MACE by 26% versus placebo.
In plain wordsIn people with heart disease, obesity and a higher risk of liver scarring, semaglutide cut major heart events by 26% compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseMACE in Fibrosis-4 >=1.3 subgroup
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Measurements
MACE reduction
26%
Fibrosis-4 >=1.3
Hazard ratio
0.74 HR
Fibrosis-4 >=1.3
Source sentences
Summary
MACE was reduced by 26% (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63-0.88; P = 0.0004)
2 context sentences(design, population, supporting numbers)
Summary · context
Subgroup analyses of the primary MACE (a composite endpoint including cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) outcome used baseline Fibrosis-4 scores ≥ 1.3, age-specific (≥1.3 ( 2.67.
Summary · context
We examined semaglutide in SELECT patients at high risk for substantial liver fibrosis in a prespecified secondary analysis.
Show in the study text Report a problemFND-4192803701
02HumanRandomized controlled trialEfficacy outcome
In patients with atherosclerotic cardiovascular disease and obesity with age-specific high Fibrosis-4 scores, semaglutide reduced MACE by 21% versus placebo.
In plain wordsIn people with heart disease, obesity and an age-adjusted higher risk of liver scarring, semaglutide cut major heart events by 21% compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseMACE in age-specific Fibrosis-4 subgroup
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Measurements
MACE reduction
21%
age-specific Fibrosis-4
Hazard ratio
0.79 HR
age-specific Fibrosis-4
Source sentences
Summary
21% (HR 0.79; 95% CI 0.63-0.98; P = 0.035)
2 context sentences(design, population, supporting numbers)
Summary · context
Subgroup analyses of the primary MACE (a composite endpoint including cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) outcome used baseline Fibrosis-4 scores ≥ 1.3, age-specific (≥1.3 ( 2.67.
Summary · context
We examined semaglutide in SELECT patients at high risk for substantial liver fibrosis in a prespecified secondary analysis.
Show in the study text Report a problemFND-4192803702
03HumanRandomized controlled trialEfficacy outcome
In patients with atherosclerotic cardiovascular disease and obesity with Fibrosis-4 above 2.67, the 34% MACE reduction with semaglutide versus placebo was not statistically significant.
In plain wordsIn people with heart disease, obesity and the highest liver scarring risk, the 34% drop in heart events with semaglutide was not statistically significant.
Peptide
Semaglutide
Outcome
No significant changeMACE in Fibrosis-4 >2.67 subgroup
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Measurements
MACE reduction
34%
Fibrosis-4 >2.67
Hazard ratio
0.66 HR
Fibrosis-4 >2.67
Source sentences
Summary
34% (HR 0.66; 95% CI 0.39-1.10; P = 0.11)
2 context sentences(design, population, supporting numbers)
Summary · context
Subgroup analyses of the primary MACE (a composite endpoint including cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) outcome used baseline Fibrosis-4 scores ≥ 1.3, age-specific (≥1.3 ( 2.67.
Summary · context
We examined semaglutide in SELECT patients at high risk for substantial liver fibrosis in a prespecified secondary analysis.
Show in the study text Report a problemFND-4192803703
04HumanRandomized controlled trialEfficacy outcome
In patients at high risk of liver fibrosis, semaglutide produced a 28% greater decrease in fatty liver index than placebo over 104 weeks.
In plain wordsIn people at high risk of liver scarring, semaglutide lowered the fatty liver index 28% more than placebo over 104 weeks.
Peptide
Semaglutide
Outcome
DecreaseFatty liver index change
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated · subcutaneous · 104 weeksAs given in this study (human).
Measurements
Fatty liver index decrease
28%
versus placebo
Source sentences
Summary
Semaglutide led to a 28% greater decrease in fatty liver index versus placebo (HR 0.72; 95% CI 0.71-0.73; P < 0.0001).
2 context sentences(design, population, supporting numbers)
Summary · context
Liver biochemical tests and steatosis risk according to fatty liver index were assessed over 104 weeks.
Summary · context
We examined semaglutide in SELECT patients at high risk for substantial liver fibrosis in a prespecified secondary analysis.
Show in the study text Report a problemFND-4192803704

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

Registered trials2

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

2 trials · 1 not yet recruiting · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

Not yet recruitingPhase not statedNCT07567378

CARTIZ Registry: Cartilage, Arthropathy and Imaging Under Tirzepatide in Zone-stratified Cohorts - A Four-Institute Mexican Observational Registry

JULIO GRANADOS MONTIELn = 30est. May 2026 to est. May 2029

Psoriatic Arthritis · Osteoarthitis · Knee · Diabetes (DM) · Type 2 Diabetes Mellitus (T2DM) · Obesity (Disorder) · Insulin Resistance Syndrome · Metabolic Syndrome · Heart Failure · Preserved Ejection Fraction · Coronary Artery Disease · Atrial Fibrillation (AF) · Non Alcholic Fatty Liver Disease · Sarcopenia · Pericardium

Trial page ClinicalTrials.govUpdated 12 May 2026

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 page ClinicalTrials.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.

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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