The Association Between Reversion of Prediabetes to Normoglycemia and Incident Cardiovascular Disease and Mortality: A Systematic Review and Meta-Analysis.
BACKGROUND Prediabetes affects approximately 470 million adults worldwide and is an established risk factor for cardiovascular disease. Whether reversion from prediabetes to normoglycemia reduces cardiovascular risk 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 through February 2026 for cohort studies and post-hoc analyses of randomized trials comparing cardiovascular outcomes in adults who reverted from prediabetes to normoglycemia versus persistent prediabetes. Hazard ratios were pooled using a DerSimonian-Laird random-effects model, with Hartung-Knapp-Sidik-Jonkman (HKSJ) sensitivity analysis. Heterogeneity was assessed using I2. Publication bias was evaluated using Egger's test. RESULTS Seven studies (71,143 participants; follow-up 2-30 years) were included. Reversion to normoglycemia was associated with significantly lower composite cardiovascular events (HR 0.72, 95% CI 0.57-0.90; P = 0.004; I2 = 76.1%) and cardiovascular mortality (HR 0.69, 95% CI 0.51-0.95; P = 0.023; I2 = 65.5%). No significant association was found for all-cause mortality (HR 0.95, 95% CI 0.88-1.02; P = 0.169). The 95% prediction interval for the primary outcome ranged from 0.37 to 1.39. Leave-one-out sensitivity analysis confirmed result stability. Egger's test showed no publication bias (P = 0.36). CONCLUSION 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 wide prediction interval warrant cautious interpretation.