Pramlintide as an Adjunct to Basal Insulin: Effects on Glycemic Control and Weight in Patients with Type 2 Diabetes Mellitus

Background: Pramlintide is a synthetic analogue of the β-cell hormone amylin. When used as an adjunct to mealtime insulin, it reduces postprandial glucose concentrations, glycosylated hemoglobin (AIC) values, and weight. Due to its effects on postprandial glucose, pramlintide may also provide similar benefits when used as an adjunct to basal insulin in the absence of mealtime insulin in patients with type 2 diabetes mellitus (DM).Objective: The current post hoc analyses examined the efficacy and tolerability of pramlintide as an adjunct to basal insulin in a subset of patients with type 2 DM in 2 clinical trials.Methods: Post hoc analyses of 2 subgroups of patients with type 2 DM treated with pramlintide and basal insulin (with or without oral agents) with no mealtime insulin are reported. One subgroup of patents was from a 52-week, randomized, double-blind, placebo-controlled study; a second subgroup of patients was from an uncontrolled, open-label study. Mean (SE) changes from baseline in A1C, postprandial glucose, weight, and insulin dose are reported. Tolerability was also assessed.Results: Baseline characteristics (mean SD]) of the placebo-controlled study were as follows: pramlintide—n = 18; age, 59 (11) years; A1C, 9.4% (1.3%); weight, 88.4 (16.5) kg; body mass index (BMI), 31.8 (6.1) kg/m²; placebo—n = 11; age, 56 (9) years; A1C, 9.4% (1.6%); weight, 92.0 (13.4) kg; and BMI, 31.2 (5.1) kg/m². Baseline characteristics (mean SD]) of the patients from the open-label study were as follows: N = 10; age, 60 (12) years; A1C, 8.1% (1.3%); weight, 109.2 (26.6) kg; and BMI, 35.7 (8.1) kg/m². In the placebo-controlled study, pramlintide treatment (120 μg BID) as an adjunct to basal insulin (neutral protamine Hagedorn, lente, or ultralente) resulted in mean (SE) reductions in A1C (pramlintide, -1.16% 0.22%]; placebo, -0.48% 0.18%]; P < 0.05) and weight (pramlintide, -2.3 1.0] kg; placebo, -0.9 1.0] kg) compared with placebo. Similarly, in the open-label study, pramlintide treatment (120 μg before major meals) as an adjunct to insulin glargine resulted in mean (SE) reductions from baseline in AIC (-0.81% 0.26%]; 95% CI, -1.40 to -0.22) and weight (-2.8 1.0] kg; 95% CI, -5.12 to -0.47). In addition, mean postprandial glucose excursions, ascertained by self-monitoring of blood glucose readings, were reduced after each meal. In both subgroups, pramlintide was generally well tolerated, and there were no episodes of severe hypoglycemia.Conclusion: The improvements in glycemic control and weight in these post hoc analyses warrant further clinical investigation into the use of pramlintide as a potential next therapeutic step in patients with type 2 DM treated with basal insulin.