Sodium-glucose co-transporter-2 inhibitors in Type 1 Diabetes: A Scoping Review

Abstract

Background. 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 (T1D) 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 T1D. Objectives. Our main goal was to systematically map the current knowledge on the efficacy and safety of SGLT2 inhibitor use in adults with T1D and present recent studies regarding the use of SGLT2 inhibitors in youth with T1D. Design. Using a scoping review approach, we searched MEDLINE to identify relevant clinical trials of SGLT2 inhibitors as adjunctive therapy to insulin in T1D published from 31-January-2012, to 31-January-2022. We included the most relevant, large-scale (> 300 participants), and long (>18 weeks) placebo controlled clinical trials of SGLT2 inhibitors as an add-on therapy to insulin in adults T1D. Additionally, we included all relevant pilot studies evaluating the use of SGLT2 inhibitors as add-on therapy to insulin in youths with T1D. Finally, we summarized data on glycaemic outcomes and potential safety concerns. Results. We identified eight placebo controlled clinical trials in adults with T1D meeting our inclusion criteria. Additionally, we identified two relevant pilot studies in youth with T1D. The clinical trials in adults with T1D confirmed the efficacy of SGLT2 inhibitors as add-on therapy to insulin. However, this was associated with an increased incidence of DKA versus placebo in all identified clinical trials. The two relevant pilot studies in youths with T1D showed promising results of SGLT2 inhibitor use as an add-on therapy to insulin, especially when combined with a fully closed-loop system. Conclusions. SGLT2 inhibitors, as an add-on therapy to insulin, improve glycaemic outcomes in adults with T1D with a potential cost of increasing the risk of DKA. The use of add-on SGLT2 inhibitors to insulin show promising results in youths with T1D. Moreover, SGLT2 inhibitors as add-on therapy in combination with closed-loop insulin therapy could provide additional benefits in improving glycemic control. The current role of SGLT2 inhibitors as an adjunct therapy to insulin in individuals with type 1 diabetes is yet to be determined.