In this small, randomised crossover study from McGill University, Canada, the authors evaluated the effects of low-dose empagliflozin (2.5 mg or 5.0 mg) as an adjunct to hybrid closed-loop insulin delivery in adults with type 1 diabetes who were unable to achieve HbA1c ≤53 mmol/mol when using either an insulin pump or a commercial closed-loop system.
Thirty-nine adults were assigned to placebo and empagliflozin 2.5 or 5.0 mg in a randomised order, with washout periods between study arms. The closed-loop system comprised a Dexcom G6 CGM device, a customised Tandem t:slim insulin pump and a smartphone containing the insulin dosing algorithms being developed at McGill. Participants entered their mealtime carbohydrate content into the system, which calculated prandial bolus doses automatically according to pre-calculated insulin:carbohydrate ratios, as well as premeal insulin levels and insulin on board. Participants could also deliver manual correction boluses.
Several participants withdrew from the study as their glycaemic control improved when using the closed-loop system on its own, leaving 24 participants who completed all three interventions. The primary outcome, mean time in range 3.9–10.0 mmol/L, was significantly higher in the empagliflozin 2.5 mg and 5.0 mg arms (71.6% and 70.2%, respectively), compared with placebo (59.0%). Results were consistent across daytime and night-time. Numerically, the lower dose of empagliflozin seemed to have the best effects on glycaemic control, although statistical comparisons between the two doses were not performed. A small but significant increase in time spent in hypoglycaemia (7 minutes per day) was observed with empagliflozin compared with placebo.
The incidence of ketone levels ≥1.5 mmol/L were rare and were all related to catheter malfunction. None resulted in ketoacidosis or required urgent care. The most common side effects of empagliflozin were thirst, increased urination and nausea, and two cases of genital mycotic infection and one of urinary tract infection occurred in two women. No serious adverse events occurred.
The study is limited by its short duration of the study interventions and the use of a research-based closed-loop system rather than a commercial one. Despite these limitations, the authors conclude that low-dose empagliflozin can improve glycaemic control in people using closed-loop therapy.