A Randomized Study and Open-Label Extension Evaluating the Long-Term Efficacy of Pramlintide as an Adjunct to Insulin Therapy in Type 1 Diabetes

Abstract

OBJECTIVE -To assess the effect of mealtime amylin replacement with pramlintide on long-term glycemic and weight control in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS-In a 52-week, double-blind, placebocontrolled, multicenter study, 480 patients with type 1 diabetes were randomized to receive preprandial injections of placebo or 30 g pramlintide q.i.d., in addition to existing insulin regimens. At week 20, pramlintide-treated patients were re-randomized to 30 or 60 g pramlintide q.i.d. if decreases from baseline in HbA 1c were Ͻ1% at week 13. Of the 342 patients who completed the 52-week study, 236 individuals (ϳ70%) elected to participate in a 1-year openlabel extension in which all patients received 30 or 60 g pramlintide q.i.d..RESULTS -Treatment with pramlintide led to a mean reduction in HbA 1c of 0.67% from baseline to week 13 that was significantly (P Ͻ 0.0001) greater than the placebo reduction (0.16%), and a significant placebo-corrected treatment difference was sustained through week 52 (P ϭ 0.0071). The greater HbA 1c reduction was associated with an average weight loss, rather than weight gain, and was not accompanied by an increased overall event rate of severe hypoglycemia. In the open-label extension, mean HbA 1c levels decreased rapidly in patients receiving pramlintide for the first time and remained at reduced levels in patients who continued pramlintide treatment. The most common adverse events reported by the pramlintide group were mild nausea and anorexia, which both occurred during the initial weeks of treatment and dissipated over time.CONCLUSIONS -Mealtime pramlintide treatment as an adjunct to insulin improved longterm glycemic control without inducing weight gain or increasing the overall risk of severe hypoglycemia in patients with type 1 diabetes. Diabetes Care 25:724 -730, 2002

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

“…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].…”

IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants

“…In humans, pramlintide reduces food intake in both T1D and control subjects (Asmar et al 2010) and induces sustained weight loss in T1D subjects (Whitehouse et al 2002, Ratner et al 2005, Edelman et al 2006. However, given the modest phenotype of IAPPdeficient animals, physiologically IAPP is likely a minor contributor to overall satiety and may act to fine-tune the more robust effects of other satiety signals.…”

Alpha cell function in type 1 diabetes

“…Pramlintide can significantly decrease post-meal glucagon levels in type 1 diabetes mellitus and trials have also shown that pramlintide reduces glucose variability by delaying gastric emptying. [51][52][53][54][55] …”