Automated Insulin Delivery with SGLT2i Combination Therapy in Type 1 Diabetes

Abstract

Background: Use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as adjunct therapy to insulin in type 1 diabetes (T1D) has been previously studied. In this study, we present data from the first free-living trial combining low-dose SGLT2i with commercial automated insulin delivery (AID) or predictive low glucose suspend (PLGS) systems. Methods: In an 8-week, randomized, controlled crossover trial, adults with T1D received 5 mg/day empagliflozin (EMPA) or no drug (NOEMPA) as adjunct to insulin therapy. Participants were also randomized to sequential orders of AID (Control-IQ) and PLGS (Basal-IQ) systems for 4 and 2 weeks, respectively. The primary endpoint was percent time-in-range (TIR) 70–180 mg/dL during daytime (7:00–23:00 h) while on AID (NCT04201496). Findings: A total of 39 subjects were enrolled, 35 were randomized, 34 (EMPA; n = 18 and NOEMPA n = 16) were analyzed according to the intention-to-treat principle, and 32 (EMPA; n = 16 and NOEMPA n = 16) completed the trial. On AID, EMPA versus NOEMPA had higher daytime TIR 81% versus 71% with a mean estimated difference of +9.9% (confidence interval [95% CI] 0.6–19.1); p = 0.04. On PLGS, the EMPA versus NOEMPA daytime TIR was 80% versus 63%, mean estimated difference of +16.5% (95% CI 7.3–25.7); p < 0.001. One subject on SGLT2i and AID had one episode of diabetic ketoacidosis with nonfunctioning insulin pump infusion site occlusion contributory. Interpretation: In an 8-week outpatient study, addition of 5 mg daily empagliflozin to commercially available AID or PLGS systems significantly improved daytime glucose control in individuals with T1D, without increased hypoglycemia risk. However, the risk of ketosis and ketoacidosis remains. Therefore, future studies with SGLT2i will need modifications to closed-loop control algorithms to enhance safety.

New therapies towards a better glycemic control in youths with type 1 diabetes

“…Garcia-Tirado et al [ 106 ] compared the use of EMPA versus no use in an AID or a PLGM setting. In both types of technical treatment, the intervention group had a significant higher TIR compared to no EMPA while the AID arm had a higher TIR also without the drug (PLGM 80% vs. 63%, +16.5%; p < 0.001; AID 81% vs 71% +9.9% p = 0.04) But also in this “protected” setting of a clinical trial one euDKA occurred.…”

Participant Experiences of Low-Dose Empagliflozin Use as Adjunct Therapy to Hybrid Closed Loop: Findings From a Randomized Controlled Trial

“…In particular, a study of longer duration may have been required to see incidents of ketosis or diabetic ketoacidosis, as was seen in a similar open-label trial using empagliflozin 5 mg as an adjunct to automated insulin delivery, where one case of ketoacidosis was observed. 11 Dedicated future qualitative studies would thus be warranted.…”

“…6,8,9 Short studies, however, have shown that SGLT inhibitors as an adjunct to this technology can increase time in the target range with reduced insulin requirements and without increasing hypoglycemia. 10 -12…”

Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes: A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective

“…A recently published free-living, placebo-controlled, cross-over study of 8 weeks duration investigating 5 mg of empagliflozin as an adjunct to advanced continuous subcutaneous insulin infusion (CSII) therapy, using either an automated insulin delivery (AID) system or a predictive low glucose suspend (PLGS) system in 39 individuals with T1D, demonstrated a significantly improved time in glycemic range in both trial arms (AID: time in glycemic range was 81% with empagliflozin versus 71% without empagliflozin; PLGS: 80% versus 63%). The risk of hypoglycemia was comparable; DKA occurred in one participant receiving empagliflozin and this was associated with a nonfunctioning insulin pump [76].…”