Study Finds Semaglutide Can Reduce Risk of Tobacco-Related Healthcare Use

Rong Xu, PhD
Credit: Case Western Reserve University

Use of semaglutide (Ozempic; Wegovy) could reduce the urge to smoke and contribute to a reduction in medical encounters related to tobacco use, according to an analysis of real-world data from more than 220,000 people with type 2 diabetes.

A series of 7 emulation target trials, results indicate use of semaglutide was associated with reductions in medical encounters for tobacco use disorder ranging from 12% to 32% relative to other antidiabetes medications. Although the full mechanism of action for GLP-1 receptor agonists is not known, results from the current study led investigators to support further research into use of semaglutide as an aid in curbing the impact of tobacco use disorder in some patients.¹

“While there are effective medications to support people if they wish to stop smoking, not everyone responds to them,” said Rong Xu, PhD, biomedical informatics professor and director of the Case Western Reserve School of Medicine’s Center for Artificial Intelligence in Drug Discovery.² “As a result of the high relapse rates, alternative medications to help people stop smoking are needed.”

Few medical therapies have seen the same upswing in attention and demand as semaglutide in recent years, driven primarily by revelations of its weight loss benefits in people with obesity. Still, with the first approval coming less than a decade ago, long-term data on use has accrued in real-time, including its apparent benefits on substance use disorders. In May 2024, a study among patients with obesity and no history of alcohol use disorder led by Xu concluded use of semaglutide was associated with a 50% to 60% lower risk for both incidence and recurrent of alcohol use disorder at 12 months relative to other antiobesity medications.^3,4

In the current study, investigators sought to build on this work by comparing the use of semaglutide against other antidiabetes medications for risk of tobacco use disorder-related medical encounters among patients with type 2 diabetes and tobacco user disorder from the TriNetX database. Leveraging the database, investigators designed 7 target emulation trials among patients with comorbid type 2 diabetes and tobacco use disorder comparing semaglutide against 7 other antidiabetes medication classes or agents for incidence of tobacco use disorder-related health care measures at 12 months.¹

Investigators defined tobacco use disorder-related health care measures as medical encounters for diagnosis of tobacco use disorder, smoking cessation medication prescriptions, and smoking cessation counseling. For the purpose of analysis, risk was assessed using Cox proportional hazards and Kaplan–Meier survival analyses. Of note, the 7 other antidiabetes medications of interest were insulins, metformin, DPP-4 inhibitors, SGLT2 inhibitors, sulfonylureas, thiazolidines, and other GLP-1 receptor agonists.¹

Investigators' initial search of the database during the period of interest yielded more than 490,000 records. Upon application of inclusion criteria and exclusion of those with coprescription of medications of interest, data from 222,942 new users of antidiabetes medications was included in the study. Of these, 5967 were new users of semaglutide and 216,975 were new users of other antidiabetes medications. Investigators pointed out comparison groups were “largely” well-balanced after propensity-score matching.¹

Results of the study indicate use of semaglutide was associated with a significant reduction in risk for medical encounters for tobacco use disorder diagnosis relative to other antidiabetes medications, with this reduction most apparent relative to insulins (hazard ratio [HR], 0.68; 95% CI, 0.63 to 0.74) and least apparent, but remaining statistically significant, relative to other GLP-1 receptor agonists (HR, 0.88; 95% CI, 0.81 to 0.96).¹

Additional analysis suggested semaglutide was associated with a significant reduction in risk for medical encounters for tobacco use disorder diagnosis relative to other antidiabetes medications, with this reduction most apparent relative to insulins (HR, 0.32; 95% CI, 0.28 to 0.38) and least apparent relative to other GLP-1 receptor agonists (HR, 0.62; 95% CI, 0.52 to 0.74). Further analysis offered evidence of a reduction in risk for smoking cessation counseling for semaglutide use compared with other antidiabetes medications, but this only achieved statistical significance reductions in comparison to insulins, metformin, and DPP-4 inhibitors. Investigators highlighted subgroup analyses revealed similar findings when assessing outcomes among those with and without concomitant obesity.¹

Investigators called out multiple limitations within their study to consider when interpreting results. These included but were not limited to this inherent with retrospective observational studies of electronic health record data, such as unmeasured or uncontrolled confounders and biases as well as overdiagnosis, underdiagnosis, and misdiagnosis.¹

“Although our results may be consistent with the hypothesis that semaglutide might be beneficial for smoking cessation, study limitations preclude firm conclusions and should not be interpreted to justify clinicians’ use of semaglutide off-label for smoking cessation. This will need to be examined in randomized clinical trials,” wrote investigators.¹

References:

1. Wang W, Volkow ND, Berger NA, et al. Association of semaglutide with tobacco use disorder in patients with type 2 diabetes: target trial emulation using real-world data. Ann Intern Med. Published online July 30, 2024. doi:10.7326/M23-2718
2. Case Western Reserve University. New study shows popular diabetes and weight-loss drugs associated with lower risk for tobacco-use disorder. Newswise. July 29, 2024. Accessed July 29, 2024. https://www.newswise.com/articles/new-study-shows-popular-diabetes-and-weight-loss-drugs-associated-with-lower-risk-for-tobacco-use-disorder.
3. Campbell P, Iapoce C. 10 years of obesity: A Decade of Advancement and challenges. HCP Live. June 23, 2023. Accessed July 29, 2024. https://www.hcplive.com/view/10-years-of-obesity-a-decade-of-advancement-and-challenges.
4. Wang W, Volkow ND, Berger NA, Davis PB, Kaelber DC, Xu R. Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population [published correction appears in Nat Commun. 2024 Jun 18;15(1):5177. doi: 10.1038/s41467-024-49655-6]. Nat Commun. 2024;15(1):4548. Published 2024 May 28. doi:10.1038/s41467-024-48780-6