Pramlintide lowered glucose excursions and was well-tolerated in adolescents with type 1 diabetes: results from a randomized, single-blind, placebo-controlled, crossover study

J Pediatr. 2009 Sep;155(3):369-73. doi: 10.1016/j.jpeds.2009.03.012. Epub 2009 May 21.

Abstract

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 microg) 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-microg dose, 93 +/- 9 pg/mL; 30-microg dose, 202 +/- 21 pg/mL) occurred approximately 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-microg dose, 4 +/- 7 pg(*)h/mL; 30-microg dose, 5 +/- 7 pg(*)h/mL; placebo, 35 +/- 9 pg(*)h/mL; glucose: 15-microg dose, 129 +/- 43 mg(*)h/dL; 30-microg dose, 132 +/- 37 mg(*)h/dL; placebo, 217 +/- 56 mg(*)h/dL). Acetaminophen C(max) decreased with pramlintide; median T(max) was delayed by approximately 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amyloid / administration & dosage*
  • Blood Glucose / drug effects
  • Child
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Glucagon / blood
  • Glucagon / drug effects
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin / administration & dosage
  • Insulin / analogs & derivatives
  • Insulin Lispro
  • Islet Amyloid Polypeptide
  • Male
  • Single-Blind Method
  • Treatment Outcome

Substances

  • Amyloid
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Insulin Lispro
  • Islet Amyloid Polypeptide
  • Glucagon
  • pramlintide