Glucagon-like peptide-1 receptor agonist and new-onset diabetes in overweight/obese individuals with prediabetes: A systematic review and meta-analysis of randomized trials

Glucagon-like peptide-1 receptor agonist (GLP-1RA) is incretin-based therapy that possessed significant glucose lowering and weight loss properties. The present study aims to analyze the efficacy of GLP-1RA in the management of overweight/obese individuals with prediabetes. A thorough search was carried out on the Cochrane Library, ClinicalTrials.gov, Scopus, and Medline databases until April 3rd, 2024, using a mix of pertinent keywords. This review incorporates randomized clinical trials (RCTs) concerning the efficacy of GLP-1RA for prediabetes. The primary outcome was regression to normoglycemia and/or progression to type 2 diabetes (T2D). We used random-effect models to examine the odds ratio (OR) and mean difference (MD). A total of eight RCTs were incorporated. The results of our meta-analysis indicated that GLP-1RA therapy was associated with higher odds of regression to normoglycemia (OR 4.80; 95%CI: 3.40–6.77, p < 0.00001, I2 = 67 %) and lower risk of progression into T2D (OR 0.27; 95%CI: 0.18–0.42, p < 0.00001, I2 = 0 %) in overweight/obese individuals with prediabetes. Administration of GLP-1RA was also associated with higher reduction in HbA1c (MD -0.28 %; p < 0.00001), fasting glucose (MD -0.45 mmol/L; p < 0.00001), and BMI (MD -1.71 kg/m2; p < 0.00001) in comparison to placebo. However, the administration of GLP-1RA was associated with higher incidence of total adverse events (TAEs), treatment discontinuation due to AEs, hypoglycemia, and gastrointestinal AEs. This study indicates that while GLP-1RA is a potent therapeutic agent for prediabetes, its adverse effects are concerning, thereby precluding its recommendation as a prediabetes therapy.