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A Double-Blind, Placebo-Controlled Trial Assessing Pramlintide Treatment in the Setting of Intensive Insulin Therapy in Type 1 Diabetes

¹ Division of Diabetes/Metabolism, San Diego VA Medical Center, San Diego, California
² Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado
³ Amylin Pharmaceuticals, San Diego, California

Address correspondence and reprint requests to Orville Kolterman, MD, Senior Vice President Clinical/Regulatory Affairs, Amylin Pharmaceuticals, 9360 Towne Centre Dr., San Diego, CA 92121. E-mail: okolterman{at}amylin.com

OBJECTIVE—To assess safety, efficacy, and tolerability of pramlintide dose escalation with proactive mealtime insulin reduction, followed by insulin optimization, in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—This 29-week, double-blind, placebo-controlled study randomized 296 patients to pramlintide or placebo as an adjunct to insulin. During initiation, pramlintide was escalated from 15 to 60 µg/meal (15-µg increments) with recommended reductions (30–50%) in mealtime insulin. Insulin was subsequently adjusted to optimize glycemic control. End points included safety and change in HbA_1c (A1C), postprandial glucose, insulin, weight, and tolerability.

RESULTS—Baseline A1C was 8.1% for both groups and at week 29 had decreased comparably (pramlintide –0.5% [95% CI –0.61 to –0.33]; placebo –0.5% [–0.63 to –0.35]). Pramlintide treatment significantly reduced postprandial glucose excursions (incremental area under the curve [AUC]_0–3h: pramlintide –175 ± 40, placebo –64 ± 38 mg · h^–1 · dl^–1; P < 0.0005) and weight (pramlintide –1.3 ± 0.30, placebo +1.2 ± 0.30 kg; P < 0.0001). At week 29, insulin dose decreased by 28 and 4% in pramlintide- and placebo-treated groups, respectively. Nausea, reported by 63 and 36% of patients in pramlintide and placebo groups (P < 0.01), respectively, was predominately mild to moderate in intensity. Severe hypoglycemia rates were low in both groups (pramlintide 0.57 ± 0.09, placebo 0.30 ± 0.06 event rate/patient-year; P < 0.05), with increased rates observed in patients remaining at 30 µg pramlintide.

CONCLUSIONS—Pramlintide dose escalation with reduced mealtime insulin was effective during therapy initiation in patients with type 1 diabetes. While both groups experienced equivalent A1C reductions relative to placebo, pramlintide-treated patients experienced reductions in postprandial glucose excursions and weight, not achievable with insulin therapy alone.

Abbreviations: AUC, area under the curve • CSII, continuous subcutaneous insulin infusion • MDI, multiple daily injection

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