Reducing the need for carbohydrate counting in type 1 diabetes using closed‐loop automated insulin delivery (artificial pancreas) and empagliflozin: A randomized, controlled, non‐inferiority, crossover pilot trial

Abstract

Aim To assess whether adding empagliflozin to closed‐loop automated insulin delivery could reduce the need for carbohydrate counting in type 1 diabetes (T1D) without worsening glucose control. Materials and Methods In an open‐label, crossover, non‐inferiority trial, 30 adult participants with T1D underwent outpatient automated insulin delivery interventions with three random sequences of prandial insulin strategy days: carbohydrate counting, simple meal announcement (no carbohydrate counting) and no meal announcement. During each sequence of prandial insulin strategies, participants were randomly assigned empagliflozin (25 mg/day) or not, and crossed over to the comparator. Mean glucose for carbohydrate counting without empagliflozin (control) was compared with no meal announcement with empagliflozin (in the primary non‐inferiority comparison) and simple meal announcement with empagliflozin (in the conditional primary non‐inferiority comparison). Results Participants were aged 40 ± 15 years, had 27 ± 15 years diabetes duration and HbA1c of 7.6% ± 0.7% (59 ± 8 mmol/mol). The system with no meal announcement and empagliflozin was not non‐inferior (and thus reasonably considered inferior) to the control arm (mean glucose 10.0 ± 1.6 vs. 8.5 ± 1.5 mmol/L; non‐inferiority p = .94), while simple meal announcement and empagliflozin was non‐inferior (8.5 ± 1.4 mmol/L; non‐inferiority p = .003). Use of empagliflozin on the background of automated insulin delivery with carbohydrate counting was associated with lower mean glucose, corresponding to a 14% greater time in the target range. While no ketoacidosis was observed, mean fasting ketones levels were higher on empagliflozin (0.22 ± 0.18 vs. 0.13 ± 0.11 mmol/L; p < .001). Conclusions Empagliflozin added to automated insulin delivery has the potential to eliminate the need for carbohydrate counting and improves glycaemic control in conjunction with carbohydrate counting, but does not allow for the elimination of meal announcement.

Strategically Playing with Fire: SGLT Inhibitors as Possible Adjunct to Closed-Loop Insulin Therapy

“…89 Though postprandial glucose levels were not reported for Haidar et al (see Table 2), the daytime time-in-range and standard deviation were significantly reduced in the empagliflozin 25 mg group on HCL compared to placebo on HCL. 86 In Biester et al 85 the areas under the curve for both meals were reduced in the dapagliflozin group compared to placebo, as was standard deviation of glucose.…”

“…Two studies have used dapagliflozin and empagliflozin as adjunct to closed-loop therapy. 85,86 In the study described in Biester et al 85 dapagliflozin 10 mg BID (2 doses) was used as adjunct to fully closed-loop; participants were given 2 mixed meal tests 6 hours apart without meal announcement. The TIR with dapagliflozin was 68% compared to 50% in the placebo arm ( P < .001), and required 22% less insulin.…”

“…In Haidar et al 86 empagliflozin 25 mg daily as adjunct to closed-loop therapy was assessed for alleviation of carbohydrate counting via 3 arms: full carbohydrate counting, simple meal announcement, or no meal announcement. The simple meal announcement with empagliflozin resulted in a daytime mean glucose of 8.5 mmol/L and daytime TIR of 68%, which was non-inferior to full carbohydrate counting alone (TIR 70% with mean glucose 8.5 mmol/L, non-inferiority P = .007).…”

Hybrid Closed-loop to Manage Gastroparesis in People With Type 1 Diabetes: a Case Series

“…Studies investigating the use of fully closed-loop systems in T1D have shown this to be a safe and effective approach to achieving target glucose outside post-prandial periods, however mitigation of post-prandial hyperglycemia remains a challenge. [45][46][47] Further studies are ongoing (NCT04877730, NCT04545567) to investigate fully closed-loop, and with the advent of faster acting insulins and dual-hormone systems, fully closed-loop therapy for T1D may become a reality in the near future.…”

Adjunctive Therapies to Optimize Closed-loop Glucose Control

“…Of note, mean fasting ketones levels were higher in participants when on empagliflozin (3.96 ± 3.24 vs. 2.34 ± 1.98 mg/dl; P < .001), but there was no occurrence of ketoacidosis. 53 Overall, strong evidence for the use of SGLT2 inhibitors as an adjunctive therapy to CL glucose control is limited, and the increased risk of ketoacidosis presents a great concern.…”