Sodium-Glucose Co-Transporter-2 Inhibitors in Type 1 Diabetes: A Scoping Review

With recent developments in diabetes technology, attaining adequate glucose control is more achievable than ever. Despite these improvements, a significant proportion of individuals with type 1 diabetes do not reach recommended glycaemic goals. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are glucose-lowering agents that inhibit the reabsorption of filtered glucose in the kidneys, thus promoting glucosuria. Because the glucose-lowering effect of SGLT2 inhibitors is achieved independently of insulin secretion, it has been speculated whether they could bridge the gap towards achieving glycaemic targets in individuals with type 1 diabetes.

Our main goal was to systematically map the current knowledge on the efficacy and safety of SGLT2 inhibitor use in adults with type 1 diabetes and present recent studies regarding the use of SGLT2 inhibitors in youth with type 1 diabetes. Using a scoping review approach, we searched MEDLINE to identify relevant clinical trials of SGLT2 inhibitors as adjunctive therapy to insulin in type 1 diabetes published from January 31, 2012, to January 31, 2022. We included the most relevant, large-scale, and long placebo-controlled clinical trials of SGLT2 inhibitors as an add-on therapy to insulin in adults with type 1 diabetes. Additionally, we included all relevant pilot studies evaluating the use of SGLT2 inhibitors as add-on therapy to insulin in youth with type 1 diabetes. We identified eight placebo-controlled clinical trials in adults with type 1 diabetes meeting our inclusion criteria and two relevant pilot studies in youth with type 1 diabetes. The clinical trials in adults with type 1 diabetes confirmed the efficacy of SGLT2 inhibitors as add-on therapy to insulin. However, this was associated with an increased incidence of diabetic ketoacidosis (DKA) versus placebo in all identified clinical trials. The two relevant pilot studies in youth with type 1 diabetes showed promising results of SGLT2 inhibitor use as an add-on therapy to insulin, especially when combined with a fully closed-loop system.

SGLT2 inhibitors, as an add-on therapy to insulin, improve glycaemic outcomes in adults with type 1 diabetes with a potential cost of increasing DKA risk. The use of add-on SGLT2 inhibitors to insulin shows promising results in youth with type 1 diabetes. Moreover, SGLT2 inhibitors as add-on therapy in combination with closed-loop insulin therapy could provide additional benefits in improving glycaemic control. The current role of SGLT2 inhibitors as an adjunct therapy to insulin in individuals with type 1 diabetes is yet to be determined.