Can GLP-1 Medications Help You Quit Smoking?

Semaglutide users are reporting reduced desire to smoke. We analyze the real-world evidence, active clinical trials, and the brain science behind the effect.

The Annals of Internal Medicine Study

In August 2024, researchers from Case Western Reserve University and the National Institute on Drug Abuse published findings that sparked widespread interest in GLP-1s for tobacco addiction. The study, published in the Annals of Internal Medicine, used electronic health records from over 220,000 smokers with type 2 diabetes.

The researchers compared semaglutide to seven other diabetes medications: insulins, metformin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas, thiazolidinediones, and other GLP-1 receptor agonists. Semaglutide outperformed all of them on tobacco-related outcomes.

What the Study Actually Measured

The researchers tracked three specific outcomes over 12 months:

• Medical encounters for tobacco use disorder diagnosis — fewer among semaglutide users
• Prescriptions for smoking cessation medications — significantly lower in the semaglutide group
• Smoking cessation counseling — reduced need in semaglutide patients

The interpretation: People on semaglutide needed less medical intervention for their smoking. This could mean they were smoking less, had fewer cravings, or both.

"The lower risks for TUD-related measures at follow-up for patients who were prescribed semaglutide are consistent with preclinical and preliminary clinical evidence in support of its potential beneficial effects." — Wang et al., Annals of Internal Medicine, 2024

The Brain Science: Why It Might Work

GLP-1 receptors aren't just in your gut — they're also expressed in brain regions that control reward and addiction. Research has identified GLP-1 receptors in the:

• Ventral tegmental area (VTA) — the dopamine-producing hub of the brain's reward system
• Nucleus accumbens — where dopamine creates feelings of pleasure and reward
• Habenula — a key region in nicotine's aversive effects

When GLP-1 receptors in these areas are activated, they appear to dampen the dopamine surge that makes addictive substances feel rewarding. The drug doesn't block the receptors nicotine targets — it modulates the reward you feel from smoking.

Active Clinical Trials

The real-world data has prompted several formal clinical trials. Here are the key ones:

Why Semaglutide Might Be Different

Earlier GLP-1 drugs showed mixed results in addiction trials. Exenatide trials for alcohol use disorder were largely negative. So why the optimism about semaglutide?

• Higher receptor binding affinity — Semaglutide binds more tightly to GLP-1 receptors than older drugs like exenatide
• Longer duration — Once-weekly dosing maintains consistent brain levels vs. twice-daily exenatide
• Greater weight loss — Fear of weight gain is a major barrier to quitting smoking; semaglutide directly addresses this
• Brain penetration — Evidence suggests semaglutide reaches reward-related brain regions more effectively

The Weight Gain Factor

One often-overlooked reason GLP-1s might help with smoking cessation: they solve the weight gain problem.

Post-cessation weight gain (PCWG) is a major reason people relapse or don't try to quit. The average person gains 4-5 kg after quitting smoking. For many, this is unacceptable. Semaglutide could theoretically:

• Reduce the reward from smoking (dopamine pathway effects)
• Prevent weight gain that often follows quitting
• Remove a major psychological barrier to attempting cessation

Current FDA Status

No GLP-1 receptor agonist is FDA-approved for smoking cessation.

Currently approved smoking cessation medications include:

• Varenicline (Chantix)
• Bupropion (Zyban/Wellbutrin)
• Nicotine replacement therapy (patches, gum, lozenges)

If ongoing clinical trials show positive results, pharmaceutical companies would need to submit data to the FDA for a new indication. This process typically takes years.

Should You Ask Your Doctor?

If you're already taking semaglutide for diabetes or weight loss and notice reduced smoking urges, that's consistent with what many patients report and what the data suggests.

However, getting a semaglutide prescription specifically for smoking cessation would be off-label use. Some considerations:

• Insurance likely won't cover it for smoking cessation alone
• Proven alternatives exist — varenicline has robust clinical trial data
• Side effects are significant — nausea, vomiting, diarrhea are common
• The evidence is preliminary — observational, not randomized controlled trials

That said, if you have obesity or diabetes AND want to quit smoking, discussing semaglutide with your doctor could address multiple goals with one medication.