OBJECTIVE: To evaluate the weight-loss effects of pramlintide. DATA SOURCES: A literature search was conducted in MEDLINE (1950-October week 4, 2009), International Pharmaceutical Abstracts (1970-October 2009), and Evidence Based Medicine Database (1991-2009 week 44) to identify relevant publications. Key words searched included pramlintide, weight loss, obesity, and overweight. Additional data sources were obtained through a bibliographic review of selected articles. STUDY SELECTION/DATA EXTRACTION: All studies conducted on humans and published in English that examined the effects of pramlintide on body weight as a primary or secondary endpoint were selected for analysis. DATA SYNTHESIS: Pramlintide is a human amylin analog approved by the Food and Drug Administration for use in conjunction with insulin therapy in patients with type 1 or 2 diabetes. In addition to its glucoregulatory actions, pramlintide has been shown to increase satiety and, therefore, decrease caloric intake via a central mechanism. Several studies show that this translates into statistically significant weight loss in overweight or obese patients with type 1 or 2 diabetes; patients with type 1 diabetes lost up to 1.7 kg over 1 year with pramlintide 60 microg 3 times daily, while patients with type 2 diabetes experienced a placebo-subtracted weight loss of up to 3.7 kg after 16 weeks of pramlintide 120-240 microg administered 3 times daily. Preliminary trials assessing the use of pramlintide for weight loss in obese patients without diabetes have demonstrated weight loss of up to 8 kg after 1 year. In all studies, the drug was generally well tolerated, with nausea being the most commonly reported adverse effect. CONCLUSIONS: Based on preliminary evidence, pramlintide facilitates modest weight loss in obese or overweight patients with and without diabetes. However, current trials were limited by inconsistent study design, dosing, and patient population.