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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
Summary
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.
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