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

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1-RAs) effectiveness in normalising prediabetes has been evaluated in recent randomised control trials (RCTs), but the data has not been synthesised to guide everyday clinical management. OBJECTIVE: To perform an updated Systematic Review (SR) and Meta-Analysis (MAs) for GLP-1 RAs' effectiveness in reversing prediabetes to normoglycemia and assess their action in clinical practice. MATERIAL AND METHODS: Search for eligible RCTs in PubMed and Cochrane Library Central Register of Controlled Trials. A SR and MA with special emphasis on studies' and participants' characteristics. GRADE assessment of overall evidence. RESULTS: All 14,564 participants in 8 RCTs had obesity disease additionally to prediabetes. GLP-1 RAs restored normoglycemia compared to placebo (OR 4.62, 95% CI 2.85, 7.49; p-value < 0.00001). Both semaglutide (OR 4.87, 95% CI 2.61, 9.09; p-value < 0.00001) and liraglutide (OR 5.43, 95% CI 1.34, 22.04; p-value 0.02) were effective but not exenatide. The assessed semaglutide's weekly dosage of 2.4 mg (mg) was effective and significance concerns studies performed across the world without post-intervention duration, and independent of cardiovascular disease (CVD). Either 1.8 mg or 3.0 mg of liraglutide daily is effective and 3.0 mg maintains post-intervention effectiveness. Semaglutide was more effective in men and liraglutide in women. They are both effective independent of patients' mean age, and intervention's duration. Heterogeneity was large (Q 84.42, p-value < 0.00001; I92%, 95% CI 77, 97%), attributed to the countries' performance and post-intervention follow-up in semaglutide-based RCTs and any subgroup analysis in liraglutide-based RCTs. The overall quality of evidence was low. CONCLUSIONS: Semaglutide and liraglutide may reverse prediabetes to normoglycemia in patients with prediabetes and obesity disease. Further research is needed for normal-weight patients with prediabetes, for semaglutide's post-intervention effect, and for liraglutide in men.