Original Title: Tobacco use is the leading cause of preventable death in the United States.1

Tobacco remains the leading cause of preventable death in the United States.1 Despite well-known harms, its use is widespread domestically and worldwide: nearly 20% of U.S. adults use tobacco products, most commonly cigarettes (12%) and electronic cigarettes (5%).2 Up to 60% of people who smoke have tried to quit, underscoring nicotine’s high addictiveness and the challenges of cessation.3

Nicotine, the addictive compound in cigarettes, electronic cigarettes, and other nicotine products, is increasingly encountered as new delivery systems gain popularity.4 About 15% of U.S. adults report current or prior e-cigarette use,5 and although the full long-term harms remain under study, cardiovascular and respiratory risks are likely.6

Effective, evidence-based treatments exist for tobacco use disorder, including nicotine replacement therapy and the FDA-approved medications bupropion and varenicline.7 While most trials focus on traditional cigarettes, growing evidence supports off-label use of these medications for e-cigarette or other nicotine product cessation.8 Still, fewer than 10% of people who use tobacco or nicotine receive a prescription medication to aid quitting.9

GLP-1 receptor agonists have recently gained attention as a potential tool to address gaps in tobacco and nicotine use treatment. This final article in a three-part series examines current evidence for GLP-1 receptor agonists in treating tobacco and nicotine use disorder.

GLP-1 Receptor Agonists in Tobacco/Nicotine Use Disorder

Preclinical studies indicate GLP-1 receptor agonists can reduce tobacco or nicotine use.10,11 Animal data suggest these agents blunt nicotine’s rewarding and reinforcing effects and reduce nicotine-seeking behavior by modulating the mesolimbic dopamine pathway.12,13 This effect mirrors the way GLP-1 receptor agonists increase food satiety and may similarly increase nicotine satiety.14

Clinical evidence is emerging. Recent quasi-experimental and randomized trials suggest GLP-1 receptor agonists may reduce tobacco or nicotine use, particularly among people with type 2 diabetes mellitus (DM2).15

A cross-sectional pilot survey studied smoking in 48 people with DM2 after starting GLP-1 receptor agonist therapy, using the Fagerström Test for Nicotine Dependence.16 Overall smoking behaviors did not change significantly, but the subgroup prescribed semaglutide (n = 11) reported fewer cigarette cravings after starting the medication than before.16

An analysis of a nationwide electronic health record database compared medical encounters related to tobacco use disorder among people with diabetes who started semaglutide versus other antidiabetic medications.17 Semaglutide users had a significantly lower risk of tobacco-related medical encounters compared with other antidiabetic medications—most notably versus insulin (hazard ratio [HR], 0.68; 95% CI, 0.63–0.74)—and a smaller reduction versus other GLP-1 receptor agonists (HR, 0.88; 95% CI, 0.81–0.96).17 Semaglutide was also associated with fewer prescriptions for smoking cessation medications compared with other antidiabetic drugs, further suggesting a potential role for GLP-1 receptor agonists in treating tobacco and nicotine use.

Randomized controlled trials provide mixed but informative results. In a double-blind, placebo-controlled trial of 255 adults with moderate to severe tobacco use disorder, dulaglutide added to behavioral counseling and oral varenicline did not significantly increase abstinence at 12 weeks but did reduce the risk of post-cessation weight gain versus placebo.18 A 12-month follow-up found no difference in abstinence at 52 weeks (32% dulaglutide vs 32% placebo), and the weight benefit seen during the 12-week course was not sustained at one year.19

Another randomized trial enrolled 84 adults who smoked and were overweight or had prediabetes; participants received exenatide or placebo alongside a 21-mg nicotine patch and counseling. After 6 weeks, exenatide increased the likelihood of 7-day point-prevalence abstinence compared with placebo (risk ratio [RR], 1.70; 95% CI, 0.96–3.27), reduced cravings and withdrawal symptoms in those who abstained, and limited post-cessation weight gain.20

A secondary analysis by Yammine et al. explored which baseline characteristics predicted greater benefit from exenatide.21 Exenatide showed more pronounced benefits versus placebo for quitting among heavier smokers (>20 cigarettes/day), people without prediabetes or obesity, and those without depressive symptoms.21

Several clinical trials of GLP-1 receptor agonists for tobacco and nicotine use are currently underway, and their results will further inform practice.23

Conclusion

Tobacco and nicotine use remain common among U.S. adults and carry serious health risks. Post-cessation weight gain is a frequent barrier to sustained quitting,23 and GLP-1 receptor agonists may offer dual benefits—reducing tobacco and nicotine cravings while limiting weight gain. Clinicians should watch the growing evidence base: although use of GLP-1 receptor agonists for tobacco or nicotine use is currently off-label, early data are promising and these agents also offer cardiometabolic benefits for people affected by tobacco use.

Click here to read the full series.

This article originally appeared on Clinical Advisor

This article was adapted from an original report published on gastroenterologyadvisor.com. All rights belong to the original publisher.