Smokers are reporting something strange: they're losing interest in cigarettes after starting GLP-1 medications for weight loss or diabetes. Anecdotal? Not anymore. There are now at least six clinical trials actively investigating whether semaglutide and other GLP-1 receptor agonists can help people quit smoking — and the first results are already in.
This page tracks every registered trial, its status, design, and what the emerging data means. We update it as new results publish.
The Observational Signal That Started It All
Before any trial launched, a massive real-world study published in the Annals of Internal Medicine in July 2024 set the scientific community buzzing. Wang, Volkow, and colleagues at Case Western Reserve analyzed electronic health records from over 222,000 patients with type 2 diabetes and co-occurring tobacco use disorder.
The study compared semaglutide against seven other anti-diabetes medications: insulin, metformin, SGLT2 inhibitors, DPP-4 inhibitors, sulfonylureas, alpha-glucosidase inhibitors, and thiazolidinediones. In every head-to-head comparison, semaglutide was associated with fewer smoking-related medical visits. The hazard ratios ranged from 0.69 to 0.85, meaning a 15-31% lower risk depending on the comparator.
This was observational, not causal — but it provided the statistical firepower to justify the clinical trials now underway.
The Active Trial Landscape
Effects of Semaglutide on Nicotine Intake and Smoking Lapse
The first human laboratory study of its kind. UNC Chapel Hill randomized smokers to semaglutide or placebo, then measured actual nicotine intake and resistance to smoking lapse in controlled lab sessions. This wasn't asking people if they smoked less — it measured what they actually did.
This is the trial to watch. Published results will be the first RCT-level evidence for GLP-1 medications and nicotine intake in humans. PI: Dr. Christian Hendershot, who also led the landmark alcohol RCT.
Semaglutide for Post-Smoking Cessation Weight Management
A different angle: can semaglutide prevent the weight gain that makes so many quit attempts fail? Post-cessation weight gain is one of the most common reasons smokers relapse. This trial pairs semaglutide 2.4mg with nicotine patches and counseling.
ONSET: Impact of Semaglutide on Tobacco Use and Related Health Behaviors
The University of Oklahoma is running a uniquely designed trial that integrates molecular biology (epigenetics), continuous glucose monitoring, and smartphone-based ecological momentary assessment to capture real-time craving and use data.
Notably, this trial recruits smokers with no immediate desire to quit — testing whether semaglutide reduces smoking even in people who aren't trying to stop.
GLP1-SC: Semaglutide for Smoking Cessation in Patients With Diabetes
The Ottawa Heart Institute is launching a Phase 3 pilot specifically for diabetic smokers — the population with the most to gain from simultaneous glycemic control and tobacco cessation.
DAL: Daily Liraglutide for Nicotine Dependence
Not semaglutide specifically, but the same drug class. This trial tested liraglutide 3.0mg (Saxenda) in overweight/obese smokers paired with 32 weeks of behavioral counseling. As an earlier-generation GLP-1RA, liraglutide's results inform the entire field.
Why GLP-1s Might Work for Nicotine
The Habenular Circuit
GLP-1 receptors are expressed in the medial habenula — a brain region that processes aversive signals from nicotine. A 2017 study in Nature Neuroscience by Tuesta et al. demonstrated that GLP-1 signaling in habenular avoidance circuits directly modulates nicotine intake in animal models. When GLP-1 receptor activity increases, the brain's "stop signal" for nicotine becomes louder.
This is the same core mechanism implicated in GLP-1 medications reducing alcohol, opioid, and food cravings — a shared reward pathway that doesn't target any single substance but alters how the brain processes reward and satiety broadly.
A comprehensive review published in Endocrine in February 2026 synthesized the full evidence base for GLP-1 receptor agonists and smoking cessation. The authors concluded that while randomized clinical trial data is still forthcoming, the convergence of preclinical evidence, observational studies, and biologically plausible mechanisms justifies the ongoing investment in clinical trials.
What This Means (and Doesn't Mean)
No GLP-1 medication is FDA-approved for smoking cessation. The observational data is compelling but does not prove causation. Off-label use for smoking cessation is not clinically supported at this time. If you want to quit smoking, talk to your doctor about FDA-approved options like varenicline (Chantix), bupropion (Wellbutrin), and nicotine replacement therapy.
That said, the trajectory of this research is accelerating. Five years ago, zero trials were registered. Today, at least six are active or completed across four countries. The UNC trial results — expected to publish in 2026 — will be the first true RCT evidence. If positive, expect a rapid expansion of larger Phase 3 trials.
For the 480,000 Americans who die from smoking every year, a new pharmacological tool — even one that helps some smokers reduce rather than quit entirely — would be significant. And unlike existing cessation medications, GLP-1 agonists would address the weight gain that derails so many quit attempts, potentially doubling the impact.
Interested in GLP-1 Treatment?
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- Wang W, Volkow ND, et al. Association of Semaglutide With Tobacco Use Disorder in Patients With Type 2 Diabetes. Annals of Internal Medicine. 2024;177(8):1016-1027.
- Tuesta LM, et al. GLP-1 acts on habenular avoidance circuits to control nicotine intake. Nature Neuroscience. 2017;20(5):708-716.
- ClinicalTrials.gov. Effects of Semaglutide on Nicotine Intake. NCT05530577. University of North Carolina, Chapel Hill.
- ClinicalTrials.gov. Semaglutide for Post-Smoking Cessation Weight Management. NCT06173778. UT Health Houston.
- ClinicalTrials.gov. ONSET: Impact of Semaglutide on Tobacco Use. NCT06986993. University of Oklahoma.
- ClinicalTrials.gov. GLP1-SC: Semaglutide for Smoking Cessation in Diabetes. NCT07059377. Ottawa Heart Institute.
- ClinicalTrials.gov. Daily Liraglutide for Nicotine Dependence. NCT03712098.
- GLP-1 receptor agonists and smoking cessation: therapeutic promise beyond glycemia. Endocrine. February 2026.