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Background:   The closed-loop (CL) system delivers insulin in a glucose-responsive manner and optimal postprandial glycemic control is difficult to achieve with the algorithm and insulin available. We hypothesized that adjunctive therapy with liraglutide, a once-daily glucagon-like peptide-1 agonist, would be more effective in normalizing postprandial hyperglycemia versus insulin monotherapy in the CL system, in patients with type 1 diabetes.Methods:   This was a randomized, controlled, open-label, crossover design trial comparing insulin monotherapy versus adjuvant subcutaneous liraglutide 1.2 mg and insulin, using the CL system in 15 patients. Blood glucose (BG), insulin, and glucagon concentrations were analyzed.Results:   The liraglutide arm was associated with overall decreased mean BG levels ( P = .0002). The average BG levels from 8:00 pm (day 1) to 9:00 pm (day 2) were lower in the liraglutide arm (144.6 ± 36.31 vs 159.7 ± 50.88 mg/dl respectively; P = .0002). Two-hour postbreakfast and lunch BG profiles were better in the liraglutide arm ( P &lt; .05) and the insulin and glucagon assay values were lower ( P &lt; .0001). Postprandially, the area under the curve (AUC) for 2-hour postbreakfast and lunch BG levels were significant ( P = .01, P = .03) and the AUC for glucagon, postbreakfast ( P &lt; .0001) and lunch ( P &lt; .05), was also significant. The incidence of hypoglycemia did not differ between arms ( P = .83, Fisher’s exact test). Overall, adjunct liraglutide therapy plus CL was well tolerated even with expected side effects.Conclusion:   This is a proof-of-concept study showing liraglutide can be a potential adjunctive therapy in addition to CL with insulin to reduce postprandial hyperglycemia in type 1 diabetes.

Adjuvant Liraglutide and Insulin Versus Insulin Monotherapy in the Closed-Loop System in Type 1 Diabetes