Pramlintide lowered glucose excursions and was well-tolerated in adolescents with type 1 diabetes: results from a randomized, single-blind, placebo-controlled, crossover study.
OBJECTIVE
To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of pramlintide in treating adolescents with type 1 diabetes.


METHODS
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.
Chase
H Peter
HP
Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO 80045-6511, USA. peter.chase@ucdenver.edu
Lutz
Karen
K
Pencek
Richard
R
Zhang
Bei
B
Porter
Lisa
L
D000293:Adolescent; D000682:Amyloid / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects; D002648:Child; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005934:Glucagon / Q000097:blood / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives; D061268:Insulin Lispro; D058228:Islet Amyloid Polypeptide; D008297:Male; D016037:Single-Blind Method; D016896:Treatment Outcome
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D058228:Islet Amyloid Polypeptide; D005934:Glucagon; C105254:pramlintide