Safety and Short-Term Cardiorenal Effects of Initiating SGLT2 Inhibitors During Ramadan Fasting in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction

Abstract

Objectives: To evaluate the safety profile and short-term renal, electrolyte, and echocardiographic changes associated with initiating SGLT2 inhibitor therapy during Ramadan fasting in clinically stable, non-diabetic patients with HFrEF. Methodology: This prospective, non-randomized comparative study enrolled 140 clinically stable non-diabetic HFrEF patients who fasted during Ramadan 2024–2025. Participants were allocated to either initiation of an SGLT2 inhibitor (dapagliflozin 10 mg or empagliflozin 10 mg once daily) in addition to guideline-directed medical therapy (SGLT2 group, n=70) or guideline-directed therapy alone (control group, n=70). Structured weekly clinical follow-up was conducted throughout Ramadan. Renal function and electrolytes were assessed at baseline and post-Ramadan. Echocardiography was performed before and after fasting. Results: Baseline characteristics were comparable between groups. Urinary tract infections were more frequent in the SGLT2 group (41.4% vs 10%, P<0.001). No significant between-group differences were observed in creatinine, urea, sodium, potassium, or left ventricular ejection fraction (LVEF) at baseline or post-Ramadan (all P>0.05). Within the SGLT2 group, creatinine and urea increased modestly but significantly (P<0.001). Both groups demonstrated small but statistically significant reductions in sodium and potassium and modest improvement in LVEF after Ramadan (P<0.001). No cases of ketoacidosis, hospitalization, or fasting discontinuation occurred. Conclusion: Initiation of SGLT2 inhibitor therapy during Ramadan in clinically stable non-diabetic HFrEF patients was not associated with major short-term safety concerns under structured monitoring. Although urinary tract infections were more frequent, no clinically significant renal deterioration or severe adverse events were observed. These findings suggest feasibility of initiation during Ramadan, though interpretation should consider the observational design.