Effi cacy and Harms of the Hypoglycemic Agent Pramlintide in Diabetes Mellitus

PURPOSE We conducted a study to examine the effi cacy, 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 random-ized controlled trials (RCTs) fulfi lling 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 ful-fi lled inclusion criteria. All trials were conducted with adults, and none was lon-ger than 52 weeks. In type 1 diabetes with intensive insulin therapy, pramlintide was as effective as placebo in lowering glycated hemoglobin (HbA1c) levels in one trial. Pramlintide was somewhat more effective than placebo in patients using conventional insulin therapy, with a between-group difference in HbA1c levels of 0.2 % to 0.3 % (2 studies). In patients with type 2 diabetes, pramlintide was more effective at reducing HbA1c levels than placebo when added to fl exibly dosed glargine (without prandial insulin) and when added to fi xed-dose insulin therapies, with or without oral hypoglycemic agents (between-group differences in HbA1c 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 HbA1c 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 HbA1c levels in the range of 0.2 % to 0.4%. Further research is needed to determine pramlint-ide’s durability of hypoglycemic effect, as well as effects on patient-reported outcomes, morbidity, mortality, and long-term harms