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

ABSTRACT 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; I 2 92%, 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.