SGLT2 Inhibitors in the Management of Type 1 Diabetes (T1D): An Update on Current Evidence and Recommendations

SGLT2i (sodium glucose transporter type 2 inhibitors) are pharmacological agents that act by inhibiting the SGLT2, by reducing the renal plasma glucose threshold and inducing glycosuria, resulting in a blood glucose lowering effect. In recent years, studies demonstrating some additional positive effects of SGLT2i also in the treatment of T1D have increased progressively. The SGLT2i dapagliflozin and sotagliflozin have been temporarily licensed for use by the European Medical Agency (EMA) as an adjunct to insulin therapy in adults with T1D with a body mass index of 27 kg/m2 or higher. However, in the meantime, the US Food and Drug Administration (FDA) Endocrinologic and Metabolic Drugs Advisory Committee was divided, citing concerns about the main side effects of SGLT2i, especially diabetic ketoacidosis (DKA). The aim of this manuscript was to conduct an update on current evidence and recommendations of the reported use of SGLT2i in the treatment of T1D in humans. Preclinical studies, clinical trial and real world data suggest benefits in glycaemia control and nefro-cardiovascular protection, even though several studies have documented an important increase in the risk of DKA, a serious and life-threatening adverse event of these agents. SGLT2i potentially addresses some of the unmet needs associated with T1D by improving glycaemic control with weight loss and without increasing hypoglycemia, by reducing glycaemic variability. However, due to side effects, EMA recommendation for SGLT2 use on T1D was withdrawn. Further studies will be needed to determine the safety of this therapy in T1D and to define the type of patient who can benefit most from these medications.