title: Adjuvant Liraglutide and Insulin Versus Insulin Monotherapy in the Closed-Loop System in Type 1 Diabetes: A Randomized Open-Labeled Crossover Design Trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, Division of Endocrinology and Diabetes, Children's Hospital at Montefiore, Bronx, NY, USA.
authors.forename: Jeniece Trast
authors.initials: JT
authors.lastname: Ilkowitz
authors.affiliation: Department of Pediatrics, Division of Endocrinology and Diabetes, Children's Hospital at Montefiore, Bronx, NY, USA.
authors.forename: Ranjitha
authors.initials: R
authors.lastname: Katikaneni
authors.affiliation: Medtronic, Northridge, CA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Cantwell
authors.affiliation: Department of Pediatrics, Division of Endocrinology and Diabetes, Children's Hospital at Montefiore, Bronx, NY, USA.
authors.forename: Neesha
authors.initials: N
authors.lastname: Ramchandani
authors.affiliation: Department of Pediatrics, Division of Endocrinology and Diabetes, Children's Hospital at Montefiore, Bronx, NY, USA Division Chief, Pediatric, Endocrinology and Diabetes, Albert Einstein College of Medicine, Children's Hospital at Montefiore, NY, USA rheptull@montefiore.org.
authors.forename: Rubina A
authors.initials: RA
authors.lastname: Heptulla
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D005934:Glucagon / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D015994:Incidence; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D007332:Insulin Infusion Systems; D000069450:Liraglutide / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; D005934:Glucagon
keywords: closed loop; glucagon like peptide-1; liraglutide; type 1 diabetes