Proteomic Changes Upon Treatment with Semaglutide in Individuals with Obesity

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2025 Jan 3

PMID 39753963

Authors

Lasse Maretty

Dipender Gill

Lotte Simonsen

Keng Soh

Loukas Zagkos

Michael Galanakis

Jonas Sibbesen

Miquel Triana Iglesias

Anna Secher

Dirk Valkenborg

Jonathan Q Purnell

Lotte Bjerre Knudsen

Abd A Tahrani

Milan Geybels

Affiliations

Soon will be listed here.

Abstract

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 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.

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