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, placebocontrolled, parallel-group, multicenter study, 656 patients with type 2 diabetes (age 57 Ϯ 10 years, diabetes duration 12 Ϯ 7 years, BMI 34.0 Ϯ 7.0 kg/m 2 , HbA 1c 9.1 Ϯ 1.2%, mean Ϯ 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 g TID, 90 g BID, or 120 g BID).RESULTS -Treatment with pramlintide 120 g BID led to a sustained reduction from baseline in HbA 1c (Ϫ0.68 and Ϫ0.62% at weeks 26 and 52, respectively), which was significantly greater than that seen with placebo (P Ͻ 0.05). The proportion of patients achieving an HbA 1c Ͻ8% was approximately twofold greater with pramlintide (120 g BID) than with placebo (46 vs. 28%, P Ͻ 0.05). The glycemic improvement with pramlintide 120 g BID was accompanied by a mean weight loss (Ϫ1.4 kg vs. ϩ0.7 kg with placebo at week 52, P Ͻ 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 g BID, as an adjunct to insulin therapy, improves long-term glycemic and weight control in patients with type 2 diabetes. Diabetes Care 26:784 -790, 2003

Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes

“…Several randomised, double-blind, placebo-controlled longterm trials on patients with type 2 diabetes have shown that the addition of pramlintide to pre-existing insulin regimens led to a further improvement in glycaemic control that was consistently accompanied by weight loss [34,35]. In recent pooled analyses of two long-term type 2 diabetes studies, 26 weeks of treatment with pramlintide (120 μg twice daily) led to a significant, placebo-corrected reduction in body weight that was progressive in nature, evident in subjects who did not report nausea, and most pronounced in subjects who were severely obese at baseline (averaging ∼3 kg in subjects with an entry BMI of >35 kg/m 2 ) [36].…”

“…A dose of 120 μg was chosen because it has been widely studied in long-term trials [33][34][35], it has been shown to elicit a sustained reduction in body weight [33][34][35][36], and is intended for clinical use in insulin-treated subjects with type 2 diabetes. The preload meal consisted of 125 g of banana blended with 150 ml of low-fat (2%) milk and 150 ml of water (estimated energy content ∼189 kcal; 6 g protein, 36 g carbohydrate, 3 g fat), and was consumed within 3 min.…”

“…Consistent with the observed glucoregulatory actions of amylin in rodents, clinical studies in insulin-treated patients with diabetes have shown that pramlintide reduces postprandial glucose excursions by suppressing glucagon secretion and slowing gastric emptying [30][31][32]. In long-term (6-12 months) clinical studies of insulin-treated type 1 or type 2 diabetic patients, adjunctive treatment with pramlintide lowered HbA 1 c levels and produced a significant and sustained reduction in body weight, particularly in those patients who were overweight at baseline [33][34][35][36].…”

Pramlintide: Clinical Strategies for Success

“…14,15 The efficacy of pramlintide as an adjunct to mealtime insulin has been demonstrated in both type 1 and type 2 diabetic patients in several long-term, double-blind, placebo-controlled trials. [17][18][19][20][21][22][23][24] In the type 1 diabetic population, after 6 months of treatment with pramlintide (30 or 60 μg, three to four times daily), the mean reduction in A1C from a baseline of ~8.9% was 0.4% (P < 0.05) compared to a reduction of 0.1% in the placebo group. On average, pramlintide patients lost 1.1 kg (P < 0.05) in body weight, as opposed to a 0.6 kg weight gain in the placebo group.…”

Obesity treatment: novel peripheral targets

“…A stable analogue of amylin, named pramlintide (Symlin; Amylin Pharmaceuticals, San Diego, CA, USA), is Obesity: peripheral targets licensed in the USA for use as an adjunct to insulin treatment in both Type 1 and Type 2 diabetes mellitus, and its use in patients with these diseases is associated with modest weight loss [181][182][183][184]. In addition, small-scale trials of its efficacy as an obesity treatment have demonstrated that it may also be of use in patients without diabetes, both as monotherapy and in combination with a leptin receptor agonist [185,186].…”