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Updated: Sep 9, 2025

Multidisciplinary Approach to Obesity Management: A Case Report
05:10

Multidisciplinary Approach to Obesity Management: A Case Report

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Cardiovascular and kidney outcomes of GLP-1 receptor agonists in adults with obesity: A target trial emulation study

Huilin Tang1,2, Yiwen Lu1,3, Bingyu Zhang1,3

  • 1The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Diabetes, Obesity & Metabolism
|August 28, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduced cardiovascular, kidney, and mortality risks in adults with obesity but no diabetes, compared to other anti-obesity medications (AOMs). Mental health also improved with GLP-1RA use.

Area of Science:

  • Endocrinology
  • Cardiology
  • Nephrology
  • Pharmacology

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are known for cardiovascular and renal benefits in type 2 diabetes.
  • Real-world data on GLP-1RA effects in individuals with obesity but without diabetes are limited.

Purpose of the Study:

  • To evaluate the cardiovascular and kidney outcomes associated with GLP-1RAs compared to other anti-obesity medications (AOMs).
  • To assess the impact of GLP-1RAs on mortality, mental health, and safety in adults with obesity and no history of diabetes.

Main Methods:

  • A target trial emulation study using TriNetX electronic health records from July 2021 to May 2025.
  • Inclusion of adults with obesity and no diabetes history who initiated GLP-1RAs (liraglutide, semaglutide, tirzepatide) or other AOMs.
  • Propensity score matching (1:1) and Cox models to analyze outcomes including MACE, MAKE, mortality, mental health conditions, and safety events.

Main Results:

  • Over 140,000 matched pairs showed GLP-1RA use was linked to lower risks of major adverse cardiovascular events (MACE) (HR 0.76) and major adverse kidney events (MAKE) (HR 0.64).
  • GLP-1RA initiators had significantly reduced all-cause mortality (HR 0.49) and improved mental health outcomes, including depression and suicidal ideation.
  • No increased risks for acute pancreatitis, hypoglycemia, or gastrointestinal symptoms were observed with GLP-1RAs.

Conclusions:

  • In adults with obesity but no diabetes, GLP-1RAs demonstrated significant benefits in reducing cardiovascular, kidney, and mortality risks compared to other AOMs.
  • GLP-1RAs also showed a positive impact on mental health outcomes in this population.
  • The findings support the use of GLP-1RAs for comprehensive health benefits beyond weight management in non-diabetic obese individuals.
Keywords:
GLP‐1 receptor agonistsanti‐obesity medicationmajor adverse cardiovascular eventsmajor adverse kidney events

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