Adjunctive Exenatide Therapy in Pediatric Type 1 Diabetes

Adjunctive exenatide therapy reduces post-prandial hyperglycemia in adolescents with Type 1 diabetes….

Exenatide improves post-prandial glycemic excursions in Type 2 diabetes. This could benefit Type 1 diabetes as well. The study aimed to determine an effective and safe glucose-lowering adjuvant exenatide dose in adolescents with Type 1 diabetes. 

Eight subjects completed a three-part double-blinded randomized controlled study of pre-meal exenatide. Two doses of exenatide (1.25 and 2.5 mcg) were compared to insulin monotherapy. Prandial insulin dose was reduced by 20%. Gastric emptying and hormones were analyzed for 300 min post-meal.

Treatment with both doses of exenatide vs. insulin monotherapy significantly reduced glucose excursions over 300 minutes (p<0.0001). Exenatide administration failed to suppress glucagon but delayed gastric emptying (p<0.004). Subjects were 17+1 yrs (range 15.8-18), had diabetes for 5+3.3 yrs, weighed 67+8.7 kg, had a BMI of 23.8+2.1, HbA1c 7.4+0.7 %, and total daily insulin dose of 0.9+0.2 units/kg/day. Postprandial hyperglycemia was reduced with 1.25 mcg and 2.5 mcg with adjunctive exenatide versus insulin monotherapy.  

Glucagon and C-peptide concentrations were not statistically different between studies using exenatide vs. insulin alone (p<0.1, p<0.06 respectively). GLP-1 was lower with 2.5 mcg exenatide compared to insulin (p<0.0001) but not with 1.25 mcg exenatide (p<0.2). 

Insulin levels were lower between exenatide groups vs. insulin alone (p<0.0001) as expected with a 20% reduction in insulin. 

Our study demonstrates reduction in postprandial glucose after exenatide injection in adolescents with Type 1 diabetes. These effects were associated with delayed gastric emptying and the results are consistent with published studies in adults. However, as opposed to previous reports, glucagon suppression was not noted with exenatide and it could be due to the small sample size of the study. 

Both exenatide doses were comparable in reducing post-prandial glucose excursions and hence the lower dose could be tested as an initial dose and titrated to response and tolerability in a larger cohort of subjects. Caution must be exercised if blood glucose is low to omit exenatide or use lowered insulin and/or exenatide dose. 

From the results it was concluded that adjunctive exenatide therapy reduces post-prandial hyperglycemia in adolescents with Type 1 diabetes. This reduction in glucose excursion occurs despite reduction in insulin dose. The researchers suggest that exenatide has therapeutic potential as adjunctive therapy in Type 1 diabetes.