Advances in Anti-obesity Pharmacotherapy: Current Treatments, Emerging Therapies, and Challenges

Obesity is a major public health concern linked to health risks such as hypertension, hyperlipidemia, type 2 diabetes mellitus (T2DM), stroke, metabolic syndrome, asthma, and cancer. It is among the leading causes of morbidity and mortality worldwide caused by an unhealthy diet and lack of physical activity, but genetic or hormonal factors may also contribute. Over a third of adults in the United States are obese. Pharmacological agents have been designed to reduce weight gain caused by excessive calorie intake and low physical activity. They work by inhibiting the absorption of dietary fat or stimulating the secretion of satiety hormones. These drugs include lipase inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. However, the current weight-loss strategies do not effectively treat genetic-related diseases, such as generalized lipodystrophy, Bardet-Biedl syndrome, and proopiomelanocortin (POMC) deficiency. Emerging therapies for these gene mutations have been developed targeting leptin and melanocortin-4 receptors (MC4Rs), restoring the normal function of leptin or melanocortin-4 receptors regulating energy balance and appetite. Leptin analogs and MC4R agonists are novel therapies that target genetic or hormonal causes of obesity. This article provides a comprehensive review of anti-obesity medications (AOMs). In this review, we discuss the clinical trials, efficacy, United States FDA-approved indication, contraindications, and serious side effects of different classes of drugs, including lipase inhibitors, GLP-1 agonists, leptin analogs, and MC4R agonists.