Pramlintide Lowered Glucose Excursions and Was Well-Tolerated in Adolescents with Type 1 Diabetes: Results from a Randomized, Single-Blind, Placebo-Controlled, Crossover Study

Objectives To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of pramlintide in treating adolescents with type 1 diabetes. Study design Twelve subjects (9 females, 3 males, age 12 to 17 years; A1C, 8.4%; body mass index, 25 kg/m(2)) were randomized to pramlintide (15 or 30 mu g) or placebo administered before a standardized breakfast. Insulin lispro (50% of usual mealtime dose) was injected separately. Acetaminophen (1000 mg) was administered orally to provide an indicator of gastric emptying rate. Results In 9 evaluable subjects, plasma pramlintide concentrations increased dose-proportionately; mean peak plasma concentration (C-max) (15-mu g dose, 93 +/- 9 pg/mL; 30-mu g dose, 202 +/- 21 pg/mL) occurred similar to 0.3 h (median time to peak concentration) after administration. Pramlintide reduced incremental area under the concentration curve (AUC(0-3h)) for glucagon and glucose versus placebo (glucagon: 15-mu g dose, 4 +/- 7 pg*h/mL; 30-mu g dose, 5 +/- 7 pg*h/mL; placebo, 35 +/- 9 pg*h/mL; glucose: 15-mu g dose, 129 +/- 43 mg*h/dL; 30-mu g dose, 132 +/- 37 mg*h/dL; placebo, 217 +/- 56 mg*h/dL). Acetaminophen C-max decreased with pramlintide; median T-max was delayed by similar to 2.6- to 3.8-fold. Pramlintide was well tolerated, and no treatment-related adverse events occurred. Conclusions Pramlintide reduced postprandial glucagon and glucose excursions and slowed gastric emptying in adolescents with type 1 diabetes, with no treatment-related adverse events. Long-term studies evaluating the efficacy and safety of pramlintide in adolescents are warranted. (J Pediatr 2009;155:369-73).