Long-term glycemic variability and the risk of heart failure: a meta-analysis

Long-term glycemic variability (GV) has emerged as a potential cardiovascular risk factor beyond average glycemic levels. However, its association with the risk of heart failure (HF) remains unclear. This meta-analysis evaluated the relationship between long-term GV and the incidence of HF in adults.

We systematically searched PubMed, Embase, and Web of Science from inception to January 31, 2025, for observational studies assessing the association between long-term GV-measured by variability indices of hemoglobin A1c (HbA1c) or fasting plasma glucose-and HF risk. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models by incorporating the influence of heterogeneity.

Eleven datasets from 10 studies involving 4,229,377 adults were included. Compared with participants with low GV, those with high long-term GV had a significantly increased risk of incident HF (HR = 1.69; 95% CI [1.38-2.06]; p < 0.001; I² = 92%). The association remained consistent in sensitivity analyses restricted to patients with type 2 diabetes, high-quality studies, and studies adjusting for mean hemoglobin A1c (HbA1c) levels (HR = 1.96, 1.78, and 1.95, respectively; all p < 0.001). Subgroup analyses revealed consistent findings across GV metrics, geographic regions, study designs, mean age, sex distribution, follow-up duration, and study quality (p for subgroup difference > 0.05). No significant publication bias was detected (Egger's test, p = 0.29).

High long-term GV is independently associated with an increased risk of HF. These findings underscore the clinical relevance of GV monitoring in cardiovascular risk assessment, including risk stratification for the incidence of HF.