Proteomic changes upon treatment with semaglutide in individuals with obesity.

Maretty L, Gill D, Simonsen L, Soh K, Zagkos L, Galanakis M, Sibbesen J, Iglesias MT, Secher A, Valkenborg D, Purnell JQ, Knudsen LB, Tahrani AA, Geybels M

Nature medicine3 Jan 2025Cited by 75 (Europe PMC)

PMID39753963PMCIDPMC11750704DOI10.1038/s41591-024-03355-2PepBankPUB-39753963

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Summary

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA_1c at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering. A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities. This study showcases the potential of proteomics data gathered from randomized trials for providing insights into disease mechanisms and drug repurposing opportunities. These data also highlight the unmet need for, and importance of, examining proteomic changes in response to weight loss pharmacotherapy in future trials.

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

Results from this study3

3 results from studies that gave the peptide. 3 results from people.

01HumanObservational studyMechanism
In adults with overweight or obesity in STEP 1 and STEP 2, semaglutide had broad effects on the circulating proteome, in processes linked to body weight, glycemic control, lipid metabolism and inflammation.
In plain wordsIn adults with overweight or obesity, semaglutide changed many blood proteins, including proteins linked to weight, blood sugar, fats and inflammation.
Peptide
Semaglutide
Outcome
MixedCirculating proteome changes
Study
n: not reported in source
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645).
Show in the study text Report a problemFND-3975396301
02HumanObservational studyMechanism
In adults with overweight or obesity, several proteins were regulated by semaglutide after accounting for changes in body weight and HbA1c, suggesting effects beyond weight loss and glucose lowering.
In plain wordsIn adults with overweight or obesity, semaglutide changed some blood proteins even after weight loss and blood sugar changes were taken into account.
Peptide
Semaglutide
Outcome
MixedProtein regulation beyond weight and HbA1c change
Study
n: not reported in source
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA_1c at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645).
Show in the study text Report a problemFND-3975396302
03HumanObservational studyMechanism
In adults with overweight or obesity, semaglutide was linked to downregulation of specific proteins associated with cardiovascular disease risk.
In plain wordsIn adults with overweight or obesity, semaglutide was linked to lower levels of some proteins associated with heart disease risk.
Peptide
Semaglutide
Outcome
DecreaseDownregulation of proteins associated with cardiovascular disease risk
Study
n: not reported in source
Outcome group
Metabolic pathways and metabolomics · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645).
Show in the study text Report a problemFND-3975396303

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

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

Subjects

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