Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes

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, HbA_1c 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 HbA_1c (−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 HbA_1c <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.