SGLT2 Inhibition in Type 1 Diabetes with Diabetic Kidney Disease: Potential Cardiorenal Benefits Can Outweigh Preventable Risk of Diabetic Ketoacidosis

The aim of this review is to summarize existing research investigating the use of sodium glucose cotransporter-2 (SGLT2) inhibitors in patients with type 1 diabetes mellitus (T1DM) while highlighting potential strategies to mitigate the risk of diabetic ketoacidosis (DKA).SGLT2 inhibitors have been studied in patients with T1DM in phase 3 clinical trials such as the inTandem, DEPICT, and EASE trials, which demonstrated consistent reductions in HbA1c. Secondary analyses of these trials have also reported potential kidney protective effects that are independent of improved glycemic control. However, trials in patients with type 2 diabetes mellitus (T2DM) have found an increased risk of DKA with SGLT2 inhibitors, a serious concern in patients with T1DM. SGLT2 inhibitors provide cardiovascular benefits and kidney protection in patients with T2DM and are a promising therapeutic option for patients with T1DM due to overlapping pathophysiological mechanisms. However, SGLT2 inhibitors increase the risk of DKA, and there is currently a lack of research investigating the beneficial effects of SGLT2 inhibitors in patients with T1DM. Preventative measure for DKA would have to be implemented and the risks would need to be carefully balanced with the benefits offered by SGLT2 inhibitors. Additional research will also be required to determine the kidney protective effects of SGLT2 inhibitors in patients with T1DM and diabetic kidney disease and to quantify the risk of DKA after the implementation of preventative measures, proper patient education, and ketone monitoring.