A Comparative Study of Safety Outcomes of Sodium Glucose Cotransporter-2 Inhibitors and Loop Diuretics Among Diabetic Patients Using Real-world Data

Sodium glucose cotransporter-2 (SGLT2) inhibitors and loop diuretics can cause volume depletion. However, the long-term safety of the concurrent use of both agents has not been widely evaluated. We conducted a retrospective observational cohort study to evaluate the safety of SGLT2 inhibitors with loop diuretics vs SGLT2 inhibitors alone among diabetic patients. The primary endpoint was a composite of volume-depletion adverse events at 1 month and 12 months. Of the 400 patients included, 98 received SGLT2 inhibitors with a loop diuretic and 302 received SGLT2 inhibitors alone. The concurrent use of SGLT2 inhibitors and loop diuretics was tolerated at 1 month; however, it resulted in a significant increase in volume-depletion events at 12 months (10.2% vs 1.7%; aHR = 7.03, 95% CI (1.80-27.37), P-value = 0.005). In conclusion, the long-term concurrent use of SGLT2 inhibitors and loop diuretics increases the risk of volume depletion, warranting frequent monitoring.