The Role of Adjunctive Exenatide Therapy in Pediatric Type 1 Diabetes

Overview

Journal Diabetes Care

Specialty Endocrinology

Date 2010 Mar 25

PMID 20332358

Citations 21

Authors

Vandana S Raman

Kimberly J Mason

Luisa M Rodriguez

Krishnavathana Hassan

Xiaoying Yu

Lisa Bomgaars

Rubina A Heptulla

Affiliations

Soon will be listed here.

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.

Citing Articles

Glucagon-like peptide-1 and impaired counterregulatory responses to hypoglycemia in type 1 diabetes.

Rocha G, de Melo F World J Diabetes. 2025; 16(2):99928.

PMID: 39959274 PMC: 11718485. DOI: 10.4239/wjd.v16.i2.99928.

Glucagon-like peptide-1 receptor agonists and type 1 diabetes: a potential game changer?.

Resnick O, Bril F, Beauchamp G Front Endocrinol (Lausanne). 2025; 15:1520313.

PMID: 39906033 PMC: 11790463. DOI: 10.3389/fendo.2024.1520313.

Mechanistic Pathways and Clinical Implications of GLP-1 Receptor Agonists in Type 1 Diabetes Management.

Delrue C, Speeckaert M Int J Mol Sci. 2024; 25(17).

PMID: 39273299 PMC: 11395482. DOI: 10.3390/ijms25179351.

Postprandial glucose metabolism in children and adolescents with type 1 diabetes mellitus: potential targets for improvement.

Maguolo A, Mazzuca G, Smart C, Maffeis C Eur J Clin Nutr. 2023; 78(2):79-86.

PMID: 37875611 DOI: 10.1038/s41430-023-01359-8.

hUCMSCs carrying exenatide prevent T1DM by improving intestinal microflora composition and islet tissue damage repair.

Wang W, Wang Y, Chi J, Tan X, Hu J, Ma X Mol Med. 2022; 28(1):155.

PMID: 36514009 PMC: 9746121. DOI: 10.1186/s10020-022-00526-0.

References

Nathan D, Genuth S, Lachin J, Cleary P, Crofford O, Davis M . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329(14):977-86. DOI: 10.1056/NEJM199309303291401. View

Nathan D, Cleary P, Backlund J, Genuth S, Lachin J, Orchard T . Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005; 353(25):2643-53. PMC: 2637991. DOI: 10.1056/NEJMoa052187. View

Rodriguez L, Mason K, Haymond M, Heptulla R . The role of prandial pramlintide in the treatment of adolescents with type 1 diabetes. Pediatr Res. 2007; 62(6):746-9. DOI: 10.1203/PDR.0b013e318159af8c. View

. Weight gain associated with intensive therapy in the diabetes control and complications trial. The DCCT Research Group. Diabetes Care. 1988; 11(7):567-73. DOI: 10.2337/diacare.11.7.567. View

Dupre J, Behme M, Hramiak I, McFarlane P, Williamson M, Zabel P . Glucagon-like peptide I reduces postprandial glycemic excursions in IDDM. Diabetes. 1995; 44(6):626-30. DOI: 10.2337/diab.44.6.626. View

Heptulla R, Rodriguez L, Bomgaars L, Haymond M . The role of amylin and glucagon in the dampening of glycemic excursions in children with type 1 diabetes. Diabetes. 2005; 54(4):1100-7. DOI: 10.2337/diabetes.54.4.1100. View

Dupre J, Behme M, McDonald T . Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes. J Clin Endocrinol Metab. 2004; 89(7):3469-73. DOI: 10.1210/jc.2003-032001. View

Nielsen L, Young A, Parkes D . Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept. 2004; 117(2):77-88. DOI: 10.1016/j.regpep.2003.10.028. View

Drucker D, Nauck M . The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006; 368(9548):1696-705. DOI: 10.1016/S0140-6736(06)69705-5. View

10.

Steil G, Rebrin K, Darwin C, Hariri F, Saad M . Feasibility of automating insulin delivery for the treatment of type 1 diabetes. Diabetes. 2006; 55(12):3344-50. DOI: 10.2337/db06-0419. View

11.

Drucker D . Enhancing the action of incretin hormones: a new whey forward?. Endocrinology. 2006; 147(7):3171-2. DOI: 10.1210/en.2006-0494. View

12.

Edelman S, 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(2):175-89. DOI: 10.1089/15209150260007390. View

13.

. 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(9131):854-65. View

14.

Aaboe K, Krarup T, Madsbad S, Holst J . GLP-1: physiological effects and potential therapeutic applications. Diabetes Obes Metab. 2008; 10(11):994-1003. DOI: 10.1111/j.1463-1326.2008.00853.x. View