SGLT2i Improves Glycemic Control in Patients With Congenital Severe Insulin Resistance

Insulin-resistant diabetes in Rabson-Mendenhall syndrome (RMS) is relatively unresponsive to first-line antidiabetic treatments, including metformin and insulin. We report 2 patients with RMS treated with 2 different sodium-glucose cotransporter inhibitors 2: empagliflozin in an 11-year-old boy and dapagliflozin in a 12-year-old girl. In the first patient, we began empagliflozin at 2.5 mg/day and increased the dose to 10 mg/day over 3 months. During treatment with empagliflozin, the amount of time during which the patient maintained serum glucose in the 70 to 180 mg/dL target range increased by 2 hours per day. Hemoglobin A1C dropped from >14% to 11.9%, urinary calcium increased almost twofold, and beta-hydroxybutyrate remained <2.5 mmol/L. Because glycemic control did not further improve with dose escalation, we reverted to the 2.5 mg/day dose. We initiated dapagliflozin in a second patient at 5 mg/day and witnessed a reduction of hemoglobin A1C from 8.5% to 6.2% after 6 months and a mild increase in urinary excretion of phosphorus but not calcium. Insulin levels fell by >50%. In 2 patients with RMS, empagliflozin and dapagliflozin were well tolerated and improved glycemic control without significantly increasing ketonemia. Renal calcium excretion should be carefully monitored.