Emerging and Established Pharmacotherapies for Smoking Cessation: A Review

Tobacco use remains the leading preventable cause of death in the United States, with well-established links to cardiovascular morbidity and mortality. Despite the availability of pharmacologic and behavioral therapies, sustained smoking cessation remains a challenge for many individuals. This narrative review evaluates both established and emerging pharmacotherapies for smoking cessation, with a focus on recent evidence supporting cytisine and glucagon-like peptide-1 receptor agonists. Varenicline and combination nicotine replacement therapy continue to demonstrate the highest efficacy among first-line agents. Cytisine, a plant-derived partial nicotinic agonist, has shown effectiveness in early trials and may offer a favorable tolerability and cost profile. Glucagon-like peptide-1 receptor agonists, particularly exenatide, may reduce post-cessation weight gain and support abstinence in metabolically at-risk populations, though results require further validation. Behavioral interventions, including counseling and contingency management, enhance pharmacologic outcomes, particularly when combined. While current therapies improve quit rates, absolute abstinence remains modest, supporting the need for further research into combination regimens, precision medicine approaches, and long-term safety of emerging treatments.