GLP-1 Drug Exenatide Nearly Doubled Smoking Quit Rates When Added to the Nicotine Patch | Research

The takeaway

Adding the GLP-1 drug exenatide to the nicotine patch nearly doubled quit rates and reduced post-cessation weight gain by 5.6 pounds in a pilot trial of overweight smokers.

46.3% vs 26.8% quit rate
Exenatide plus nicotine patch nearly doubled smoking abstinence compared to patch alone, with 5.6 lbs less weight gain

What the researchers found

When added to the nicotine patch, exenatide (a GLP-1 receptor agonist) nearly doubled smoking quit rates: 46.3% of the exenatide group achieved abstinence versus 26.8% on placebo (risk ratio 1.70, posterior probability 96.5%). Exenatide also reduced cravings in the overall sample and withdrawal symptoms among those who quit.

Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (posterior probability 97.4%), addressing one of the most common barriers to quitting — weight gain. Adverse events were higher in the exenatide group (9.5% vs 2.3%) but the treatment was generally tolerable.

Why it matters

Smoking remains the leading cause of preventable death, and current quit medications have modest success rates. This trial is among the first to test a GLP-1 drug for smoking cessation in humans, building on animal studies showing GLP-1 receptor agonists reduce nicotine's rewarding effects. The dual benefit — higher quit rates plus less weight gain — makes this approach especially compelling since fear of gaining weight keeps many smokers from trying to quit.

The numbers in context

n=84; 46.3% vs 26.8% abstinence; RR=1.70; 5.6 lbs less weight gain; 2 mg exenatide weekly; 21 mg nicotine patch; 6 weeks; PP=96.5% for abstinence; PP=97.4% for weight; AEs 9.5% vs 2.3%

How the study worked

This was a pilot randomized controlled trial. Eighty-four prediabetic and/or overweight smokers were randomly assigned 1:1 to receive either once-weekly exenatide (2 mg subcutaneous injection) or placebo. All participants also received a 21 mg nicotine patch and brief smoking cessation counseling. Abstinence was verified by expired carbon monoxide levels (≤5 ppm) at 6 weeks. The study used Bayesian statistical analysis to quantify evidence for treatment effects.

Who was studied

84 prediabetic and/or overweight adult smokers

What this study cannot tell us

This was a small pilot study with only 84 participants and a short 6-week treatment period. The sample was limited to prediabetic and/or overweight smokers, so results may not generalize to all smokers. Longer follow-up is needed to determine whether quit rates persist. Adverse events were more common with exenatide. The study was not powered for definitive conclusions — larger confirmatory trials are needed.

How to read the evidence

This is a randomized controlled trial, which is a strong study design, but it's a small pilot study (84 participants) with a short 6-week duration. The Bayesian analysis provides strong posterior probabilities but the study was not designed to be definitive. Moderate evidence that warrants larger confirmatory trials.

When this study was published

Published in 2021, this is recent and relevant research. It predates the explosion of interest in GLP-1 drugs for non-metabolic conditions but is part of the same trend.

The bigger picture

This trial is part of a growing body of research suggesting GLP-1 drugs affect the brain's reward system beyond just food. Anecdotal reports of reduced interest in alcohol, nicotine, and other substances among GLP-1 users have prompted formal studies. If larger trials confirm these results, GLP-1 agonists could become a new tool in addiction medicine — not just for weight loss and diabetes.

Questions still open

Would newer, more potent GLP-1 drugs like semaglutide show even stronger effects on smoking cessation?
Do the quit-rate benefits persist beyond the 6-week treatment window, or do smokers relapse when the drug is stopped?
What is the mechanism by which GLP-1 receptor activation reduces the rewarding effects of nicotine in the brain?

Common questions

Can GLP-1 drugs help you quit smoking?

This pilot study suggests they might. Exenatide, a GLP-1 receptor agonist, nearly doubled quit rates when added to the nicotine patch. Animal studies show GLP-1 drugs reduce nicotine's rewarding effects in the brain, and this is among the first human trials to test that theory. However, larger studies are needed to confirm these early results.

Why do people gain weight when they quit smoking?

Nicotine suppresses appetite and increases metabolism. When people stop smoking, their appetite returns and metabolism slows, leading to an average weight gain of 5-10 pounds. This study found that exenatide — which also suppresses appetite — offset this effect, with quitters gaining 5.6 pounds less than those on placebo.

Read the original research

Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: A Pilot Randomized Controlled Trial.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 23(10), 1682-1690

View on PubMed ↗Publisher’s paper ↗

Citation

Yammine, Luba; Green, Charles E; Kosten, Thomas R; de Dios, Constanza; Suchting, Robert; Lane, Scott D; Verrico, Christopher D; Schmitz, Joy M. (2021). Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: A Pilot Randomized Controlled Trial.. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 23(10), 1682-1690. https://doi.org/10.1093/ntr/ntab066