INTRODUCTION: Obesity is a chronic disease and a major global health challenge. Apart from bariatric surgery, which is costly and not without risk, there are currently no successful long-term treatment options for obesity. The history of pharmacological agents for obesity has been turbulent with many examples of drugs being removed from the market due to significant side effects. Orlistat and sibutramine (the latest drugs on the market) provide only modest weight loss and are both associated with high attrition rates due to intolerable side effects. Furthermore, sibutramine was recently withdrawn from the market. There is a need for the development of safe and efficacious drug treatments for obesity. AREAS COVERED: This review covers the history of leptin therapy as an orphan drug, leptin-replacement therapy as a treatment for obesity, preclinical studies showing the efficacy of leptin/amylin combination and finally, the very promising early clinical findings using pramlintide/meteleptin combination therapy in overweight to obese individuals. EXPERT OPINION: Combination pharmacological therapy, such as pramlintide/metreleptin, for the treatment of obesity is very promising and is supported by encouraging weight loss results and improvement in metabolic makers in early-phase clinical studies. However, the latest randomized clinical trial on pramlintide/metreleptin was recently stopped due to safety concerns.
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