Pharmacological Management of Obesity: An Evidence-Based Review of Emerging Anti-Obesity Drugs and Their Clinical Applications

Obesity is now recognized as a chronic, relapsing neurohormonal disease rather than a failure of willpower, yet effective pharmacological treatment has only recently become available. The last decade has witnessed a revolution driven by gut-derived incretin hormones. This review provides a comprehensive overview of emerging anti-obesity drugs, from molecular mechanism to clinical application and future outlook. Semaglutide and tirzepatide exert their effects through central appetite regulation, delayed gastric emptying, and improved insulin sensitivity. In clinical trials, they have achieved unprecedented weight loss of up to 20.9%, with a substantial proportion of patients reaching ≥15% reduction in body weight. Importantly, cardiovascular outcome data now support a role for these drugs in risk reduction, with semaglutide showing significant reductions in MACE in high-risk patients with obesity. The safety profile is favorable, dominated by mild to moderate nausea and gastrointestinal symptoms that wane over time. Despite efficacy, major challenges persist. Treatment costs exceed $1000 per month in many regions, access is inequitable, and discontinuation leads to regain of approximately two-thirds of lost weight within one year. Novel agents in development aim to address these gaps. Oral GLP-1 receptor agonists and triple agonists targeting GIP, GLP-1, and glucagon receptors promise greater convenience and efficacy. Concurrently, advances in AI and digital biomarkers may enable precision prescribing and proactive dose adjustment. Ultimately, the integration of these new pharmacotherapies with lifestyle intervention and behavioral support represents the future standard of care for obesity.

Semaglutide and tirzepatide, Gastrointestinal, GIP

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