SGLT Inhibitors for Type 1 Diabetes: Proceed With Extreme Caution

Intensive insulin management is currently the only option for effective treatment of type 1 diabetes. Recent data from the T1D Exchange (T1DX) registry (1), which comprises leading U.S. diabetes treatment centers, show that despite the widespread availability of insulin analogs and increasing use of insulin pumps and continuous glucose monitoring systems, only about 20% of adult patients achieve the A1C target of <7% (53 mmol/mol) recommended by the American Diabetes Association (2). It is reasonable to assume that glycemic control of patients receiving care outside of major centers might be even worse. The T1DX registry has also shown that nearly 5% of adult participants experienced one or more episodes of diabetic ketoacidosis (DKA) within the past 12 months (3), and the Centers for Disease Control and Prevention recently reported a 6.3% annual increase in hospitalization rates for DKA from 2009 to 2014, with highest rates in persons aged <45 years (4). Moreover, the majority of patients are either overweight or obese, potentially increasing their risk of cardiovascular disease (1). There is clearly an unmet need for noninsulin adjunctive therapies that improve glycemic control without increasing the risk of hypoglycemia or contributing to weight gain, and it is noteworthy that among nearly 50,000 pediatric and adult participants in the T1DX registry in the U.S. and the Prospective Diabetes Follow-up (DPV) registry in Germany and Austria, two large consortia of diabetes centers, adjuvant medications are being used off-label by 5.4% of participants in T1DX and 1.6% in DPV (5). Sodium–glucose cotransporter 2 (SGLT2) inhibitors block the SGLT2 transporter in the proximal renal tubule resulting in glucosuria and natriuresis and are approved and indicated for type 2 diabetes. Dual SGLT1+2 inhibitors have the additional effect of inhibiting SGLT1 in the gastrointestinal tract, thereby delaying intestinal absorption of glucose and galactose. Owing to …