The Association Between Reversion of Prediabetes to Normoglycemia and Incident Cardiovascular Disease and Mortality: A Systematic Review and Meta-Analysis

OBJECTIVE: Prediabetes affects ∼470 million adults worldwide and is an established risk factor for cardiovascular disease. Whether reversion from prediabetes to normoglycemia reduces the risk of cardiovascular disease remains uncertain. We conducted a systematic review and meta-analysis to quantify this association with major cardiovascular events, cardiovascular mortality, and all-cause mortality. METHODS: We searched PubMed, Embase, CENTRAL, Web of Science, and Scopus to February 2026 for cohort studies and post hoc analyses of randomized trials comparing cardiovascular outcomes in adults who reverted from prediabetes to normoglycemia vs those with persistent prediabetes. Hazard ratios were pooled using a DerSimonian-Laird random-effects model, with Hartung-Knapp-Sidik-Jonkman sensitivity analysis. Heterogeneity was assessed using I². Publication bias was evaluated using Egger's test. RESULTS: Seven studies (71,143 participants; follow-up 2 to 30 years) were included. Reversion to normoglycemia was associated with significantly lower composite cardiovascular events (HR 0.72, 95% CI 0.57 to 0.90; p=0.004; I²=76.1%) and cardiovascular mortality (HR 0.69, 95% CI 0.51 to 0.95; p=0.023; I²=65.5%). No significant association was found for all-cause mortality (HR 0.95, 95% CI 0.88 to 1.02; p=0.169). The 95% prediction interval for the primary outcome ranged from 0.37 to 1.39. Leave-one-out sensitivity analysis confirmed the stability of the results. Egger's test revealed no publication bias (p=0.36). CONCLUSIONS: Reversion from prediabetes to normoglycemia is associated with significant reductions in cardiovascular events and cardiovascular mortality, supporting early identification and management of prediabetes as a cardiovascular prevention strategy. The observational nature of the evidence and the wide prediction interval warrant cautious interpretation.