Adjunctive Therapy with the Amylin Analogue Pramlintide Leads to a Combined Improvement in Glycemic and Weight Control in Insulin-Treated Subjects with Type 2 Diabetes

Abstract

The objective of this study was to assess the effect of mealtime amylin replacement with pramlintide on long-term glycemic and weight control in subjects with type 2 diabetes. This 52-week, randomized, placebo-controlled, multicenter, double-blind, dose-ranging study in 538 insulin-treated subjects with type 2 diabetes compared the efficacy and safety of 30-, 75-, or 150-microg doses of pramlintide, a synthetic analogue of the beta-cell hormone amylin, to placebo when injected subcutaneously three times daily (TID) with major meals. Pramlintide therapy led to a mean reduction in HbA1c of 0.9% and 1.0% from baseline to week 13 in the 75- and 150-microg dose groups, which was significant compared to placebo (p = 0.0004 and p = 0.0002, respectively). In the 150-microg dose group, there was a mean reduction in HbA1c of 0.6% from baseline to week 52 (p = 0.0068 compared to placebo). The greater reduction in HbA1c with pramlintide was achieved without increases in insulin use or severe hypoglycemia, and was accompanied by a significant (p < 0.05) reduction in body weight in all dose groups compared to placebo. Three times the proportion of subjects in the 150-microg pramlintide group compared to the placebo group achieved a concomitant reduction in both HbA1c and body weight from baseline to week 52 (48% versus 16%). The most common adverse event reported with pramlintide treatment was nausea, which was mild to moderate and dissipated early in treatment. The results from this study support the safety and efficacy of pramlintide administered three times a day with major meals, in conjunction with insulin therapy, for improving long-term glycemic and weight control in subjects with type 2 diabetes.

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].…”

The Impact of Diabetes and Associated Cardiometabolic Risk Factors on Members: Strategies for Optimizing Outcomes

“…46 A reduction in A1C of 0.5%-0.7% was achieved without increases in insulin use or significant increases in severe hypoglycemia 40 ( Figure 8). [46][47] It has also been shown that pramlintide decreases C-reactive protein and increases adiponectin, both of which are associated with inflammation and insulin resistance. The most common adverse event reported was mild to moderate nausea that dissipated early in treatment.…”

“…Pramlintide is administered 3 times a day with major meals in conjunction with insulin therapy to improve glycemic control. 47 Incretin-related therapies-GLP-1 is secreted in the small and large intestine in response to a meal along with glucose-dependent insulinotropic peptide (GIP). 48 Both regulate blood glucose by stimulating glucose-dependent insulin secretion, inhibiting gastric emptying, and inhibiting glucagon secretion.…”