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Cardiovascular changes produce unfavorable outcomes including arterial hypertension and diabetes, which are related to the increased risk of heart failure (HF). The latter is highly prevalent in the setting of glucose metabolism dysregulation and high hemodynamic load, and identifying predictors of the incidence of HF with preserved ejection fraction (HFpEF) requires a research and is a clinical need. Toward this end, the variability in glucose regulation represents a novel dynamic way to comprehend and study the impact of glycemia. The results of the published study highlight the independent association of glycated hemoglobin A1c variability with the development of HFpEF in hypertensive diabetic patients. Based on the above, the effect of diverse antidiabetic therapies on glycemic control variability and overall management of these patients to reduce the risk of HFpEF remain essential for the modern cardiologist.