Edelman S et al. (2006) A double-blind, placebo-controlled trial assessing pramlintide treatment in the setting of intensive insulin therapy in type 1 diabetes. Diabetes Care 29: 2189–2195

Amylin, a pancreatic hormone cosecreted with insulin, is involved in the regulation of postprandial blood glucose levels. The amylin analog pramlintide is used as a supplement to insulin treatment in patients with type 1 diabetes, because it improves control of hyperglycemia; in the initial trials, however, pramlintide also increased nausea and the risk of severe hypoglycemia. In a double-blind, randomized trial, Edelman and colleagues assessed whether the effect of pramlintide could be optimized by administering gradually increasing doses of pramlintide while simultaneously reducing doses of mealtime insulin, which was not done in previous studies.

In total, 296 adult patients who had used intensive insulin therapy for at least 1 year were randomly allocated to receive either pramlintide or placebo while continuing their insulin regime. Pramlintide treatment was started at a dose of 15 µg per meal, followed by a gradual increase (by 15 µg per meal per week, over 4 weeks) to 60 µg per meal, which was used throughout the 25-week maintenance period. Meanwhile, the insulin dose was adjusted according to blood glucose levels, which were monitored by the patients. Pramlintide substantially reduced postprandial elevations of glucose levels during the 29-week trial compared with placebo. Mean body weight and mealtime insulin doses were also markedly reduced in the pramlintide group compared with the placebo group. In both groups, patients experienced only mild or moderate nausea and nonsevere hyperglycemia.

The authors conclude that gradual dose escalation of pramlintide increases its tolerability, while the concomitant reduction of insulin dose increases the safety of the protocol compared to that used in previous trials, and results in favorable glycemic and body weight changes.