Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: A 1-year randomized controlled trial

Abstract

OBJECTIVE - Mealtime amylin replacement with the human amylin analog pramlintide, as an adjunct to mealtime insulin replacement, reduces postprandial glucose excursions in patients with type 2 diabetes. The aim of the present study was to assess the long-term efficacy and safety of pramlintide in this patient population. RESEARCH DESIGN AND METHODS - In a 52-week, double-blind, placebo-controlled, parallel-group, multicenter study, 656 patients with type 2 diabetes (age 57 ± 10 years, diabetes duration 12 ± 7 years, BMI 34.0 ± 7.0 kg/m2, HbA1c 9.1 ± 1.2%, mean ± SD) treated with insulin (alone or in combination with sulfonylureas and/or metformin) were randomized to receive additional preprandial subcutaneous injections of either placebo or pramlintide (60 μg TID, 90 μg BID, or 120 μg BID). RESULTS - Treatment with pramlintide 120 μg BID led to a sustained reduction from baseline in HbA1c (-0.68 and -0.62% at weeks 26 and 52, respectively), which was significantly greater than that seen with placebo (P < 0.05). The proportion of patients achieving an HbA1c <8% was approximately twofold greater with pramlintide (120 μg BID) than with placebo (46 vs. 28%, P < 0.05). The glycemic improvement with pramlintide 120 μg BID was accompanied by a mean weight loss (-1.4 kg vs. +0.7 kg with placebo at week 52, P < 0.05) and occurred without an overall increase in the severe hypoglycemia event rate. The most common adverse event associated with pramlintide use was transient, mild-to-moderate nausea. CONCLUSIONS - Mealtime amylin replacement with pramlintide 120 μg BID, as an adjunct to insulin therapy, improves long-term glycemic and weight control in patients with type 2 diabetes.