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/m²) were randomized to pramlintide (15 or 30 μg) 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-μg dose, 93 ± 9 pg/mL; 30-μg dose, 202 ± 21 pg/mL) occurred ∼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-μg dose, 4 ± 7 pg^∗h/mL; 30-μg dose, 5 ± 7 pg^∗h/mL; placebo, 35 ± 9 pg^∗h/mL; glucose: 15-μg dose, 129 ± 43 mg^∗h/dL; 30-μg dose, 132 ± 37 mg^∗h/dL; placebo, 217 ± 56 mg^∗h/dL). Acetaminophen C_max decreased with pramlintide; median T_max was delayed by ∼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.

AUC, Area under the concentration curve, C_max, Peak plasma concentration, CI, Confidence interval, CV, Coefficient of variation, CL/F, Apparent clearance, DCCT, Diabetes Control and Complications Trial, GLP-1, Glucagon-like peptide-1, LS, Least squares, SE, Standard error, t_1/2, Terminal elimination half-life, T_max, Time to first peak concentration, V/F, Apparent volume of distribution