Efficacy and harms of the hypoglycemic agent pramlintide in diabetes mellitus

PURPOSE: We conducted a study to examine the efficacy, effectiveness, and harms of pramlintide as adjunct therapy in adults and children with type 1 or type 2 diabetes. METHODS: We searched multiple bibliographic databases to January 2010, the US Food and Drug Administration Web site, and other sources to identify randomized controlled trials (RCTs) fulfilling inclusion criteria. Syntheses were qualitative because data were too heterogeneous for meta-analysis. RESULTS: Three published RCTs in type 1 diabetes and 4 in type 2 disease fulfilled inclusion criteria. All trials were conducted with adults, and none was longer than 52 weeks. In type 1 diabetes with intensive insulin therapy, pramlintide was as effective as placebo in lowering glycated hemoglobin (HbA_1c) levels in one trial. Pramlintide was somewhat more effective than placebo in patients using conventional insulin therapy, with a between-group difference in HbA_1c levels of 0.2% to 0.3% (2 studies). In patients with type 2 diabetes, pramlintide was more effective at reducing HbA_1c levels than placebo when added to flexibly dosed glargine (without prandial insulin) and when added to fixed-dose insulin therapies, with or without oral hypoglycemic agents (between-group differences in HbA_1c were approximately 0.4%). Weight loss was observed with pramlintide in both type 1 and type 2 diabetes, whereas placebo-treated patients tended to gain weight. Pramlintide-treated patients experienced more frequent nausea and severe hypoglycemia compared with patients treated with placebo. CONCLUSIONS: Pramlintide was somewhat more effective than placebo as adjunct therapy for improving HbA_1c levels and weight in adults with type 1 diabetes on conventional insulin therapy, or type 2 diabetes and inadequate glycemic control with their current therapies, with between-group differences in HbA_1c levels in the range of 0.2% to 0.4%. Further research is needed to determine pramlintide's durability of hypoglycemic effect, as well as effects on patient-reported outcomes, morbidity, mortality, and long-term harms.