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Glucagon-Like Peptide-1 Receptor Agonists: Their Potential Role in Prediabetes
Theodoros Panou1, Evanthia Gouveri1, Djordje S Popovic2,3
1Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
Summary
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show promise in managing prediabetes, reducing type 2 diabetes mellitus (T2DM) progression and improving glycemic control. While beneficial, effects on normoglycemia are not fully sustained after drug cessation.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Pharmacology
Background:
- Prediabetes significantly elevates the risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease.
- Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for T2DM and obesity treatment, with emerging evidence for prediabetes.
- Limited but promising data exist regarding the efficacy of GLP-1RAs in prediabetes management.
Purpose of the Study:
- To review the current evidence on the use of GLP-1RAs in individuals with prediabetes.
- To evaluate the impact of GLP-1RAs on T2DM progression, glycemic control, and cardiovascular outcomes in prediabetes.
- To assess the safety profile and potential benefits for associated conditions like MASLD.
Main Methods:
- Systematic review of existing studies and clinical trial data on GLP-1RAs (liraglutide, semaglutide, tirzepatide) in prediabetes.
- Analysis of outcomes including T2DM incidence, glycated haemoglobin (HbA1c), fasting glucose, weight, insulin sensitivity, and cardiovascular events.
- Evaluation of safety data, focusing on adverse effects and potential benefits for liver health.
Main Results:
- GLP-1RAs demonstrated reduced T2DM incidence and delayed progression compared to control groups.
- Significant improvements were observed in normoglycaemia, HbA1c levels, fasting glucose, and weight loss.
- Benefits included enhanced insulin sensitivity, improved beta-cell function, and reduced cardiovascular risk, particularly with tirzepatide. Liver dysfunction improvements were noted.
- Gastrointestinal adverse effects were the most common, generally mild-to-moderate. Normoglycemic effects showed partial sustainability post-withdrawal.
Conclusions:
- GLP-1RAs show significant potential in managing prediabetes by mitigating T2DM progression and improving metabolic parameters.
- While effective, the long-term sustainability of normoglycemia requires further investigation, alongside the full spectrum of cardiovascular and liver benefits.
- Larger randomized controlled trials are necessary to definitively establish the role and optimal use of GLP-1RAs in prediabetes care.
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