Is pramlintide a safe and effective adjunct therapy for patients with type 1 diabetes?

BACKGROUND Islet amyloid polypeptide ( IAPP) is a glucoregulatory hormone that maintains postprandial glucose homeostasis. The addition of IAPP to treatment regimens could, therefore, improve glycemic control in patients with diabetes. OBJECTIVE To assess the efficacy and safety of pramlintide ( an IAPP analog) for the treatment of patients with type 1 diabetes whose glucose levels are poorly controlled by intensive insulin therapy. DESIGN AND INTERVENTION Patients with type 1 diabetes were enrolled in this 29-week, double-blind, placebo-controlled, multicenter, randomized trial. Inclusion criteria included age >= 18 years, treatment with multiple daily injections or continuous sub cutaneous infusion of insulin for > 1 year, glycated hemoglobin (HbA(1c)) levels 7.5 - 9.0%, and no episodes of severe hypoglycemia for 6 months before enrollment. Patients receiving oral antidiabetic medications and antiobesity agents were excluded. Participants were randomly allocated to receive pramlintide or placebo, administered 3 - 4 times daily before meals. The starting dose of 15 mu g per meal was increased incrementally to a maximum dose of 60 mu g per meal during the 4-week initiation period. The mealtime insulin dose was reduced by 30 - 50% during this period. The pramlintide dose remained fixed throughout the 25-week maintenance period, but the insulin dose was adjusted to maintain glycemic targets. Study visits were weekly during the initiation period and monthly thereafter. Postprandial glucose levels were measured in a subset of the participants after a standardized meal test. OUTCOME MEASURES The primary outcome measure was the incidence of adverse events. Secondary outcome measures included the change from baseline in HbA(1c) levels, postprandial glucose levels, insulin dose, and body weight. RESULTS At enrollment, the pramlintide and placebo groups comprised 148 and 147 patients, respectively. Although adverse events were generally mild or moderate, the occurrence of adverse events resulted in eight withdrawals from the pramlintide group and three withdrawals from the placebo group. Reduced appetite, nausea and vomiting were more common in the pramlintide group than the placebo group. Both groups experienced a similar incidence of hypoglycemia, although the incidence was increased in the subgroup of patients who received 30 mu g pramlintide. When compared with placebo, the mean incremental postprandial glucose level was reduced in the group treated with pramlintide ( P = 0.0002). Patients in the pramlintide group were more likely to achieve the American Diabetes Association glycemic targets than those in the placebo group; however, the mean change in HbA1c level was similar in the two groups. At study end, the daily insulin dose was reduced by similar to 12% in the pramlintide group but increased by similar to 1% in the placebo group. Patients treated with pramlintide also experienced an appreciable weight loss, whereas patients in the placebo group had a mean weight gain. CONCLUSION The addition of pramlintide to intensive insulin therapy improved glycemic control in patients with type 1 diabetes.