Adults with type 1 diabetes spent more time in range with empagliflozin 2.5 mg or 5 mg as an adjunctive therapy to hybrid closed-loop insulin therapy compared with placebo, according to a speaker.

“We look at large trials assessing hybrid closed-loop therapy in type 1 diabetes and 34% to 69% of the participants do not actually achieve the target HbA1c post-intervention,” Melissa-Rosina Pasqua, MD, an endocrinologist and PhD candidate at the McGill University Health Center Research Institute in Montreal, said during a presentation at the International Conference on Advanced Technologies & Treatments for Diabetes. “When we look at other ways to reduce HbA1c, SGLT2 inhibitors as an adjunct to insulin therapy have been shown to reduce HbA1c in type 1 diabetes. The caveat is there is risk for diabetic ketoacidosis, particularly euglycemic. … The objective of our study was to assess the effect of low-dose empagliflozin on glucose control in adults with type 1 diabetes on a hybrid closed-loop system who did not otherwise get the target time in range of 70% or more.”

Researchers conducted a double-blind, crossover, randomized controlled trial enrolling 24 adults with type 1 diabetes and a baseline HbA1c between 7% and 10.5% (50% men; mean age, 33 years). The trial consisted of three 14-day intervention periods in which participants received empagliflozin 2.5 mg (Jardiance, Boehringer Ingelheim/Eli Lilly), empagliflozin 5 mg or placebo as an adjunct to hybrid closed-loop insulin therapy. The order of therapies was randomly sequenced. Continuous glucose monitoring outcomes were obtained during the last 10 days of each intervention period. Morning ketone levels were collected daily.

At the conclusion of the study, adults had a 71.6% time in range with empagliflozin 2.5 mg and a 70.2% time in range with empagliflozin 5 mg compared with a 59% time in range with placebo (P < .0001). The associations were not affected by time of day, as adults had a higher time in range with either empagliflozin dose compared with placebo during both daytime and nighttime.

Time in hypoglycemia did not differ between those receiving empagliflozin 2.5 mg and placebo. Adults had a higher time in hypoglycemia with empagliflozin 5 mg than placebo (1.5% vs. 1%; P = .0051). However, the association of higher time in hypoglycemia with empagliflozin 5 mg compared with placebo was only significant during daytime hours (1.1% vs. 0.7%; P = .0065).

Participants used 54 insulin U per day with empagliflozin 2.5 mg and 52.9 U with empagliflozin 5 mg compared with 59.2 U with placebo. Morning ketone levels were similar with both empagliflozin doses and placebo.

No serious adverse events were reported during the study and there were no episodes of DKA or severe hypoglycemia.

“There were some limitations,” Pasqua said. “It was a short, small study. We powered for time in range, we didn’t power necessarily for ketone data.”

In addition, Pasqua noted the cohort had a mean BMI of 28.8 kg/m² and insulin requirements that suggested they were mostly low-risk participants. She said studies are being planned to further explore the impact of empagliflozin on time in range in a larger cohort of adults with type 1 diabetes.