Abrupt Smoking Cessation Due to Sensory Aversion Following Tirzepatide Initiation

More than 1 billion people smoke cigarettes worldwide; roughly half are projected to die prematurely of tobacco-related disease.¹ Long-term abstinence rates remain low, especially among patients with psychiatric conditions,^2,3 and the reported average number of quit attempts before achieving long-term abstinence is 6.⁴ Although current medication-assisted treatments (MATs) for nicotine use disorder (NUD), including nicotine replacement therapy, bupropion, and varenicline, offer some benefit, return-to-use rates remain high.⁴ Emerging evidence shows that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may alter reward pathways and behaviors associated with the use of substances like nicotine,⁵ and abstinence rates reported in some studies are nearly double that of presently approved pharmacotherapy.⁶ We present a case of sudden, sustained smoking cessation associated with the initiation of tirzepatide and highlight a novel possible mechanism of action for this effect.

Case Report

A 53-year-old woman with a history of type 2 diabetes mellitus (T2DM), posttraumatic stress disorder, anxiety, depression, and hypertension and 36-pack/year smoking history presented for routine psychiatric follow-up. She reported a habit of smoking within minutes of waking up, which places her in the high category on the Fagerström Test for Nicotine Dependence.⁷ She had previously abstained for a year with varenicline treatment but relapsed after discontinuing the drug for its mood-altering side effect.

The patient was started on tirzepatide (a dual GLP-1RA and glucose-dependent insulinotropic polypeptide) for T2DM in 2023 and slowly titrated from 2.5 mg to the current 10-mg dose. Within 3 weeks of initiation, she noted that cigarettes suddenly tasted abnormal, described as “chemicals lit on fire.” She reported experiencing disgust with the smell of cigarettes and associated nausea and vomiting with each attempt to smoke.

Remarkably, she maintained abstinence for 2 years and counting. Despite periodic cravings, she could not tolerate the smell or taste of cigarettes. She acknowledged occasional but extremely rare vaping. In addition to smoking cessation, she reported a decrease in weight from 235 lb to 156 lb, attributed to the effects of tirzepatide. She considered tirzepatide the determining factor in her smoking cessation journey, stating “whatever craving receptor in my brain that wanted the cigarette was lowered after I started this medicine.”

Discussion

Several intriguing features of this case are worth highlighting. First, her prior cessation attempt and high baseline nicotine dependence are both poor prognostic indicators for abstinence, yet her abstinence of 2 years and counting exceeds expected return-to-use outcomes. Second, rather than the gradual effects seen with most MAT, the aversive effects of the GLP-1RA in her case were abrupt, a result of altered gustatory perception. Finally, the GLP-1RA induced significant weight loss. Though unsurprising, it is worth noting, as postcessation weight gain is a common phenomenon that causes patients to avoid initiating cessation, drives return to use, and is not meaningfully addressed by current MAT options for NUD.⁵

Available evidence supports the potential for application of GLP-1RAs in the treatment of NUD.^5,8 Regarding possible mechanisms, GLP-1 is synthesized by taste buds and modulates taste signaling, and GLP-1RAs have been found to alter gustatory sensation, providing a plausible mechanism for altered palatability of cigarettes.⁹ GLP-1RAs also act on mesolimbic dopamine pathways, modulating synaptic availability of dopamine and expression of dopamine reuptake transporters, thereby impacting motivation and reward behaviors and reducing nicotine reinforcement.⁵

Limitations of this case report include reliance on patient self-report without biochemical verification of abstinence. Weight loss and lifestyle changes could also be confounding. However, the temporal relationship, abrupt sensory aversion, and sustained abstinence strongly implicate tirzepatide as the driver of smoking cessation and prolonged abstinence for this patient.

This case underscores the possibility of a promising effect of tirzepatide and other GLP-1RAs on smoking cessation, and to our knowledge, it is the first to demonstrate sensory aversion as a possible causal mechanism. Although promising, further research is necessary to formally assess GLP-1RAs as potential therapy for NUD.

Article Information

Published Online: July 30, 2026. https://doi.org/10.4088/PCC.25cr04174
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(4):25cr04174
Submitted: December 21, 2025; accepted February 26, 2026.
To Cite: Ceesay OI, Rokusek B, Rasmussen J, et al. Abrupt smoking cessation due to sensory aversion following tirzepatide initiation. Prim Care Companion CNS Disord 2026;28(4):25cr04174.
Author Affiliations: College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska (Ceesay, Rokusek, Rasmussen, DeWolf); Department of Psychiatry, University of Nebraska Medical Center, Omaha, Nebraska (Ojha); College of Nursing, Seattle University, Seattle, Washington (Delsol).
Rashmi Ojha, MD is the senior author.
Corresponding Author: Omar I. Ceesay, RN, BSN, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska ([email protected]).
Financial Disclosure: None.
Funding/Support: None.
Acknowledgments: The authors would like to acknowledge Muhammed Ceesay, PharmD, Ohio State University Hospital, Columbus, Ohio; Afuthal Ssemakula, RN-BSN, PMH-BC, El Camino Hospital, San Mateo, California; Christine Delsol, MA, San Francisco, California; and Kenneth Costa (retired) for their review and editorial contribution prior to submission. The acknowledged individuals report no conflicts of interest.
Patient Consent: Consent was received from the patient to publish the case report, and information, including dates, has been de-identified to protect patient anonymity.