(DCP076) LOW-DOSE EMPAGLIFLOZIN AS ADJUNCT TO HYBRID CLOSED-LOOP INSULIN THERAPY IN SUB-OPTIMALLY CONTROLLED ADULTS WITH TYPE 1 DIABETES: A RANDOMIZED CROSSOVER CONTROLLED TRIAL

Background: SGLT inhibitors have both benefits and risks as adjunct to type 1 diabetes therapy. The primary aim was to assess whether low doses of empagliflozin as adjunct to hybrid closed-loop therapy improve glycemia compared to placebo in adults with type 1 diabetes who are not able to achieve targets with the system alone.

METHODS AND RESULTS: A double-blind, crossover, randomized controlled trial was performed in sub-optimally controlled (HbA1c 7.0-10.5%) adults who were not able to achieve a target time-in-range (3.9-10.0 mmol/L) ≥ 70% after 14 days of hybrid closed-loop therapy. Three 14-day interventions were performed with placebo, empagliflozin 2.5 mg, or empagliflozin 5 mg, as adjunct to the McGill Artificial Pancreas. Participants were assigned in a 1:1:1:1:1:1 ratio with blocked randomization. The primary outcome was percentage of target time-in-range. Other analyses include glycemic outcomes based on CGM, non-glycemic outcomes (e.g. point-of-care ketone testing, insulin dosing), and patient-reported outcomes. Analysis was by intention to treat and a p-value of less than 0.05 was regarded as significant. This trial is registered, NCT04450563.
24 participants completed the study (50% male, age 33 ± 14 yrs, HbA1c 8.1 ± 0.5%). The mean (standard deviation) percentage of target time-in-range was 59.0 (9.0) % for placebo, 71.6 (9.7) % for empagliflozin 2.5 mg, and 70.2 (8.0) % for empagliflozin 5 mg (p < 0.0001 between empagliflozin 2.5 mg and placebo, and empagliflozin 5 mg and placebo). Mean daily capillary ketone levels were not different between arms. There were no statistical differences in scores for the following quality-of-life questionnaires between interventions: Diabetes Distress Scale, Fear of Hypoglycemia Questionnaire, INSPIRE questionnaire. The qualitative analysis of semi-structured interviews done after the trial revealed there was a relatively positive experience to low-dose empagliflozin use in the trial, and that adjunctive therapy is of interest to those who conducted the study. There were no serious adverse events, diabetic ketoacidosis, or severe hypoglycemia in any intervention.

Conclusion: Empagliflozin 2.5 mg and 5 mg increased the target time-in-range on hybrid closed-loop therapy by 11–13 percentage points compared to placebo, in those who otherwise were unable to attain glycemic targets. Future studies are required to assess long-term efficacy and safety.