The role of adjunctive exenatide therapy in pediatric type 1 diabetes

Vandana S Raman, Kimberly J Mason, Luisa M Rodriguez, Krishnavathana Hassan, Xiaoying Yu, Lisa Bomgaars, Rubina A Heptulla, Vandana S Raman, Kimberly J Mason, Luisa M Rodriguez, Krishnavathana Hassan, Xiaoying Yu, Lisa Bomgaars, Rubina A Heptulla

Abstract

Objective: Exenatide improves postprandial glycemic excursions in type 2 diabetes. Exenatide could benefit type 1 diabetes as well. We aimed to determine an effective and safe glucose-lowering adjuvant exenatide dose in adolescents with type 1 diabetes.

Research design and methods: Eight subjects completed a three-part double-blinded randomized controlled study of premeal exenatide. Two doses of exenatide (1.25 and 2.5 microg) were compared with insulin monotherapy. Prandial insulin dose was reduced by 20%. Gastric emptying and hormones were analyzed for 300 min postmeal.

Results: Treatment with both doses of exenatide versus insulin monotherapy significantly reduced glucose excursions over 300 min (P < 0.0001). Exenatide administration failed to suppress glucagon but delayed gastric emptying (P < 0.004).

Conclusions: Adjunctive exenatide therapy reduces postprandial hyperglycemia in adolescents with type 1 diabetes. This reduction in glucose excursion occurs despite reduction in insulin dose. We suggest that exenatide has therapeutic potential as adjunctive therapy in type 1 diabetes.

Trial registration: ClinicalTrials.gov NCT00456300.

Figures

Figure 1
Figure 1
Glucose (A), breath analysis (B), glucagon (C), GLP-1 (D), C-peptide (E), and insulin (F) concentrations with insulin monotherapy (•), 1.25 μg (■) and 2.5 μg of exenatide (□) after a mixed meal.

References

    1. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977–986
    1. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B: Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005;353:2643–2653
    1. Edelman SV, Weyer C: Unresolved challenges with insulin therapy in type 1 and type 2 diabetes: potential benefit of replacing amylin, a second beta-cell hormone. Diabetes Technol Ther 2002;4:175–189
    1. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854–865
    1. Weight gain associated with intensive therapy in the Diabetes Control and Complications Trial. The DCCT Research Group. Diabetes Care 1988;11:567–573
    1. Steil GM, Rebrin K, Darwin C, Hariri F, Saad MF: Feasibility of automating insulin delivery for the treatment of type 1 diabetes. Diabetes 2006;55:3344–3350
    1. Drucker DJ: Enhancing the action of incretin hormones: a new whey forward? Endocrinology 2006;147:3171–3172
    1. Aaboe K, Krarup T, Madsbad S, Holst JJ: GLP-1: physiological effects and potential therapeutic applications. Diabetes Obes Metab 2008;10:994–1003
    1. Nielsen LL, Young AA, Parkes DG: Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept 2004;117:77–88
    1. Drucker DJ, Nauck MA: The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368:1696–1705
    1. Heptulla RA, Rodriguez LM, Bomgaars L, Haymond MW: The role of amylin and glucagon in the dampening of glycemic excursions in children with type 1 diabetes. Diabetes 2005;54:1100–1107
    1. Rodriguez LM, Mason KJ, Haymond MW, Heptulla RA: The role of prandial pramlintide in the treatment of adolescents with type 1 diabetes. Pediatr Res 2007;62:746–749
    1. Dupré J, Behme MT, McDonald TJ: Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes. J Clin Endocrinol Metab 2004;89:3469–3473
    1. Dupre J, Behme MT, Hramiak IM, McFarlane P, Williamson MP, Zabel P, McDonald TJ: Glucagon-like peptide I reduces postprandial glycemic excursions in IDDM. Diabetes 1995;44:626–630

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever