Impact of Disease Duration on the Effects of Pramlintide in Type 1 Diabetes: A Post Hoc Analysis of Three Clinical Trials.

INTRODUCTION: Adjunctive mealtime use of the amylin analog pramlintide improves postprandial hyperglycemia in patients with type 1 diabetes. This post hoc analysis of three randomized trials evaluated whether disease duration affected responses to pramlintide.

METHODS: Patients received mealtime pramlintide 30 or 60 µg (n = 714) or placebo (n = 537) as an adjunct to insulin and were stratified into tertiles by diabetes duration at baseline. Efficacy and safety end points were assessed at week 26 using analysis of covariance and logistic regression models.

RESULTS: Disease durations for tertiles 1, 2, and 3 were 6.7, 16.5, and 29.9 years, respectively. In all tertiles, pramlintide resulted in greater reductions in glycated hemoglobin (HbA1c) and weight than placebo, with greater weight reductions and insulin sparing in tertiles 2 and 3. Insulin dose and weight increased in the placebo group in all tertiles. Baseline HbA1c was a predictor of HbA1c lowering in both treatment groups (P < 0.0001); higher daily insulin predicted a smaller percent increase in insulin dose for placebo (P = 0.01); and higher body weight predicted greater weight loss in both pramlintide- and placebo-treated patients (P < 0.05). Event rates for severe hypoglycemia were similar for pramlintide and placebo and increased with longer duration of diabetes for both groups. Nausea with pramlintide increased with longer disease duration.

CONCLUSION: Mealtime pramlintide resulted in greater reductions in HbA1c than placebo, regardless of diabetes duration at baseline. Longer disease duration appeared to augment insulin sparing and weight loss with pramlintide, with a potential for increased incidence of hypoglycemia and nausea.

FUNDING: The design and conduct of the study were supported by Amylin Pharmaceuticals, San Diego, CA, USA.