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 < .05) and the insulin and glucagon assay values were lower ( P < .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 < .0001) and lunch ( P < .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.

Background:Diabetes ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM). Reducing DKA admissions in children with T1DM requires a coordinated, comprehensive management plan. We aimed to decrease DKA admissions, 30-day readmissions, and length of stay (LOS) for DKA admissions.Methods:A multipronged intervention was designed in 2011 to reach all patients: (1) increase insulin pump use and basal-bolus regimen versus sliding scales, (2) transform educational program, (3) increased access to medical providers, and (4) support for patients and families. A before-after study was conducted comparing performance outcomes in years 2007-2010 (preintervention) to 2012-2014 (postintervention) using administrative data and Wilcoxon rank sum and Fischer exact tests.Results:DKA admissions decreased by 44% postintervention (16.7 vs 9.3 per 100 followed patient-years; P = .006), unique patient 30-day readmissions decreased from 20% to 5% postintervention (P = .001), and median LOS significantly decreased postintervention (P < .0001). Although not an original goal of the study, median hemoglobin A1C of a subset of the population transitioned from sliding scale decreased, 10.3% to 8.9% (P < .02).Conclusions:When clinical and widespread program interventions were used, significant reductions in DKA hospitalizations, 30-day readmissions, and LOS occurred for pediatric T1DM. Continuous performance improvement efforts are needed for improving DKA outcomes.

Sitagliptin may be considered as an adjunct therapy in a closed-loop setting. Larger studies are needed to determine the role of oral agents like sitagliptin to lower postprandial hyperglycemia with closed loop.