Abstract
Visit-to-visit variability in glycated hemoglobin (HbA1c) reflects long-term instability in glycemic control, potentially contributing to cardiovascular complications. However, the association between HbA1c variability and heart failure (HF) risk remains unclear. This meta-analysis aimed to quantify the relationship between HbA1c variability and the risk of incident HF in adults. A systematic search of PubMed, Embase, and Web of Science was conducted to identify relevant studies. Observational studies and post-hoc analyses of clinical trials evaluating the association between visit-to-visit HbA1c variability and incident HF were included. Random-effects models were employed to pool hazard ratios (HRs) with 95% confidence intervals (CIs), accounting for potential heterogeneity. A total of nine studies (n = 342,123) were included in the analysis. Overall, high HbA1c variability was associated with an increased risk of HF (pooled HR = 1.78, 95% CI: 1.39-2.27, p < 0.001; I² = 87%). Sensitivity analyses restricted to patients with type 2 diabetes (HR = 1.73, 95% CI: 1.35-2.22), high-quality studies (HR = 1.82, 95% CI: 1.32-2.50), or studies adjusting for mean HbA1c (HR = 1.68, 95% CI: 1.31-2.16) produced consistent results. Subgroup analyses indicated a stronger association in prospective cohorts (HR = 2.51) compared to retrospective or post-hoc studies (p for subgroup difference < 0.001). Meta-regression analysis revealed no significant modifying effects of age, sex, follow-up duration, or study quality (p all > 0.05). In conclusion, greater visit-to-visit HbA1c variability may be associated with an increased risk of incident HF, underscoring the prognostic importance of maintaining stable long-term glycemic control in patients with type 2 diabetes.