Pharmacologic strategies that reverse prediabetes may help reduce progression to type 2 diabetes. A systematic review and meta-analysis published in Diabetes Metabolism: Research and Reviews evaluated the effectiveness of GLP-1 RAs in restoring normoglycemia in adults with prediabetes and obesity.

The analysis included 8 randomized controlled trials enrolling 14,564 participants. All participants had obesity in addition to prediabetes. Trials compared GLP-1 RAs with placebo, and outcomes focused on reversion to normoglycemia. Study characteristics, participant features, and intervention duration were assessed, and overall certainty of evidence was graded.

Across the pooled population, GLP-1 RAs increased normoglycemia restoration compared with placebo, with an odds ratio of 4.62 (95% CI, 2.85 to 7.49; P < 0.00001). Semaglutide was associated with significant benefit (odds ratio 4.87; 95% CI, 2.61 to 9.09; P < 0.00001), as was liraglutide (odds ratio 5.43; 95% CI, 1.34 to 22.04; P = 0.02). Exenatide did not demonstrate a significant effect.

Heterogeneity across studies was high (I² 92%) and was attributed to geographic differences and post-intervention follow-up in semaglutide-based trials, as well as limited subgroup analyses in liraglutide-based trials. Sex-specific analyses suggested greater effectiveness of semaglutide in men and liraglutide in women. The overall quality of evidence was rated as low, indicating the need for further studies evaluating long-term outcomes and broader patient populations.