NICOTINE-SEEKING behaviours and activity in the brain’s reward pathway are dampened through the activation of glucose-like peptide-1 receptors, a 2026 systematic review has found.
Exenatide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), performed the best in enhancing abstinence from nicotine.
GLP-1RA Benefits in Nicotine Abstinence
Investigating the implications that GLP-1RAs hold for nicotine use disorder, researchers analysed 12 studies: eight human and four preclinical.
Among the human studies, exenatide showed the most robust efficacy in enhancing abstinence from nicotine, as well as reducing craving and weight gain.
Whilst it conferred metabolic benefits, dulaglutide did not improve abstinence.
Semaglutide exhibited indirect behavioural benefits in real-world observational data.
Researchers emphasised the promising neurobehavioural and metabolic effects of GLP-1RAs, particularly exenatide and semaglutide, in smoking cessation.
They highlighted the potential of their dual mechanism effect to address limitations in current pharmacotherapies.
Dr Shatavisa Mukherjee, School of Tropical Medicine, Kolkata, India, said: “GLP-1RAs may represent a new class of cessation adjuncts that align addiction treatment with cardiometabolic risk reduction—most immediately for smokers with obesity or diabetes.
“Translation into broad tobacco-control practice will definitely hinge on durability of abstinence effects, tolerability, cost, and access, so policy should prioritize targeted implementation and definitive pragmatic trials rather than immediate guideline expansion.
“Broadly speaking, this work signals a shift towards integrating tobacco treatment within chronic disease management frameworks, encouraging clinicians and policymakers to view smoking cessation not as a standalone behavioural goal, but as part of comprehensive cardiometabolic risk reduction strategies embedded within routine care.”
Tobacco Use: Public Health Threat
Tobacco use remains the leading preventable cause of morbidity and mortality worldwide.
According to WHO, tobacco kills up to half of its users who don’t quit, totalling more than 7 million people annually, including an estimated 1.6 million non-smokers who are exposed to second-hand smoke.
Smokers also generally gain weight when they quit smoking, another challenge that GLP-1RAs may help address.
Current therapies for nicotine use disorder include nicotine replacement products such as patches, gum, lozenges, inhalators, and mouth and nasal sprays, as well as oral treatments that reduce cravings, including varenicline and bupropion.
Researchers emphasised that current treatments used to help people quit smoking in the long-term provide suboptimal abstinence.
References
Bhaduri G et al. GLP-1 receptor agonists and smoking cessation: therapeutic promise beyond glycemia. Endocrine. 2026;91(1):82.
World Health Organization. Tobacco. 2025. Available at: https://www.who.int/news-room/fact-sheets/detail/tobacco. Last accessed: 5 March 2026.
U.S. Food & Drug Administration. How smoking can increase risk for and affect diabetes. 2024. Available at: https://www.fda.gov/tobacco-products/health-effects-tobacco-use/how-smoking-can-increase-risk-and-affect-diabetes. Last accessed: 5 March 2026.
NHS England. NHS stop smoking services help you quit. 2022. Available at: https://www.nhs.uk/live-well/quit-smoking/nhs-stop-smoking-services-help-you-quit/. Last accessed: 5 March 2026.
Featured image: Nopphon on Adobe Stock
