The Role of Adjunctive Exenatide Therapy in Pediatric Type 1 Diabetes

Vandana S. Raman, MD; Kimberly J. Mason, RN; Luisa M. Rodriguez, MD; Krishnavathana Hassan, MD; Xiaoying Yu, MS; Kisa Bomgaars, MD; Rubina A. Heptulla, MD

Disclosures

Diabetes Care. 2010;33(6):1294-1296. 

In This Article

Abstract and Introduction

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 μg) 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.

Introduction

Intensive insulin therapy delays/prevents complications associated with type 1 diabetes.[1,2] However, insulin monotherapy fails to achieve normoglycemia.[3] Postprandial hyperglycemia and hypoglycemia[4,5] continue to create impediments to management. Even the closed-loop system fails to normalize postprandial hyperglycemia.[6] Additional therapies to insulin are needed to achieve optimal glycemic control.

Glucagon-like peptide (GLP)-1 is an incretin secreted in response to nutrient ingestion.[7] Physiological GLP-1 enhances insulin secretion, delays gastric emptying, and suppresses glucagon. But because of its short half-life,[8] it is unsuitable for clinical application.

Exenatide is a long-acting GLP-1 receptor agonist and acts similarly to native GLP-1.[9] Exenatide is effective in decreasing postprandial hyperglycemia in type 2 diabetes.[10] However, there are few studies using exenatide in type 1 diabetes and none in adolescents. The objective of our study was to examine the effect of adjuvant premeal exenatide and insulin on postprandial glucose in type 1 diabetes and establish an effective and safe glucose-lowering dose.

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