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Updated: Aug 22, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
11:10

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Published on: November 16, 2011

Cardiometabolic Effects of Dual GLP-1 and Glucagon Receptor Agonists: A Systematic Review and Meta-analysis of

Johann Roessler1, Michael A Nauck2, Arash Haghikia1

  • 1Cardiology and Rhythmology, University Hospital St Josef-Hospital Bochum, Ruhr University Bochum, Bochum, Germany.

Diabetes Care
|August 21, 2026
PubMed
Abstract

Insights

Dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonists significantly reduce body weight and improve cardiometabolic risk factors. These agents show greater triglyceride reduction compared to selective GLP-1R agonists.

Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology
  • Cardiovascular Disease Research

Background:

  • Selective glucagon-like peptide-1 receptor (GLP-1R) agonists are established for weight reduction and cardiometabolic risk factor improvement.
  • The impact of dual GLP-1R and glucagon receptor (GCGR) agonism on these cardiometabolic effects requires clarification.

Purpose of the Study:

  • To assess the effects of dual GLP-1R/GCGR agonists on cardiometabolic risk factors.
  • To compare the efficacy of dual agonists versus selective GLP-1R agonists in a meta-analysis of randomized controlled trials.

Main Methods:

  • A random-effects meta-analysis of randomized controlled trials (RCTs) was conducted.
  • Searches included MEDLINE, Embase, and CENTRAL databases up to June 21, 2026.
  • Primary outcome: placebo-corrected change in body weight; Secondary outcomes: changes in waist circumference, lipids, HbA1c, and hemodynamics.

Main Results:

  • Sixteen RCTs with 6,611 participants were included.
  • Dual GLP-1R/GCGR agonists significantly reduced body weight by -7.44% compared to placebo.
  • Dual agonists demonstrated greater triglyceride reduction (-0.28 mmol/L) versus selective GLP-1R agonists.

Conclusions:

  • Dual GLP-1R/GCGR agonists consistently improve cardiometabolic risk factors.
  • These agents may offer metabolic benefits exceeding those of selective GLP-1R agonists.
  • Further large-scale outcome studies are warranted to confirm these findings.

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