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Effectiveness of GLP-1 RAs in Restoring Normoglycemia in Patients With Prediabetes: An Updated Systematic Review and

Georgios I Tsironikos1, Vasiliki Tsolaki2, George Zakynthinos3

  • 1Department of Research for General Medicine and Primary Health Care, Faculty of Medicine, University of Ioannina, University Campus, Ioannina, Greece.

Diabetes/Metabolism Research and Reviews
|December 16, 2025
PubMed
Abstract

Insights

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) like semaglutide and liraglutide can reverse prediabetes to normoglycemia in individuals with obesity. These medications show significant effectiveness, guiding clinical practice for prediabetes management.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Prediabetes affects a significant portion of the population, increasing cardiovascular risk.
  • Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have emerged as potential therapeutic agents for prediabetes.
  • Existing randomized control trials (RCTs) on GLP-1 RAs for prediabetes require synthesis to inform clinical practice.

Purpose of the Study:

  • To conduct a systematic review and meta-analysis on the effectiveness of GLP-1 RAs in reversing prediabetes to normoglycemia.
  • To assess the practical application of GLP-1 RAs in managing prediabetes.
  • To evaluate the impact of GLP-1 RAs based on patient and study characteristics.

Main Methods:

  • Systematic literature search of RCTs in PubMed and Cochrane Library.
  • Meta-analysis focusing on study and participant characteristics.
  • GRADE assessment of the overall quality of evidence.

Main Results:

  • GLP-1 RAs significantly restored normoglycemia compared to placebo in 14,564 participants with prediabetes and obesity (OR 4.62).
  • Semaglutide (2.4 mg weekly) and liraglutide (1.8-3.0 mg daily) were effective, while exenatide was not.
  • Effectiveness was observed regardless of age, intervention duration, or cardiovascular disease status; semaglutide showed higher efficacy in men, liraglutide in women.

Conclusions:

  • Semaglutide and liraglutide show promise in reversing prediabetes to normoglycemia in patients with co-existing obesity.
  • Further research is warranted for normal-weight individuals with prediabetes.
  • Additional studies are needed to explore the post-intervention effects of semaglutide and the efficacy of liraglutide in men.
Keywords:
GLP‐1 RAsdiabetesimpaired fasting glucoseimpaired glucose toleranceprediabetes

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