Researchers designed a randomized controlled trial to test whether the GLP-1 receptor agonist exenatide can help overweight or prediabetic smokers quit by reducing cravings and withdrawal symptoms.
First human RCT of GLP-1 for smokingThis trial represents one of the earliest formal randomized clinical trials testing whether a GLP-1 receptor agonist can help people quit smoking — a concept now gaining widespread attention.
What the researchers found
This is a study protocol, not a results paper. The planned trial will randomize 90 prediabetic and/or overweight smokers 1:1 to exenatide extended-release or placebo, both combined with transdermal nicotine replacement therapy (NRT) and behavioral counseling.
Outcomes include smoking abstinence (verified by expired CO ≤5 ppm), craving (Questionnaire of Smoking Urges), and withdrawal symptoms (Wisconsin Scale), assessed weekly during 6 weeks of treatment and at 1 and 4 weeks post-treatment. Cue-induced craving will be measured using virtual reality exposure at baseline and 3 weeks. The hypothesis is that exenatide will increase complete abstinence rates and reduce craving and withdrawal above standard NRT alone.
Why it matters
Smoking remains the leading preventable cause of death, and existing cessation medications have modest success rates. If GLP-1 drugs can reduce nicotine cravings and withdrawal through their effects on brain reward circuits, they could become a powerful new tool for smoking cessation — especially for the many smokers who are also overweight or prediabetic and could benefit from the metabolic effects simultaneously. This trial represents the first human test of this concept.
How the study worked
Double-blind, placebo-controlled, randomized clinical trial. Ninety treatment-seeking smokers who are prediabetic and/or overweight will be enrolled. Participants receive either exenatide once weekly or placebo, plus standard nicotine patches and behavioral counseling. Assessments occur weekly for 6 treatment weeks and at 1 and 4 weeks post-treatment. Virtual reality cue exposure is used to assess triggered cravings.
What this study cannot tell us
As a protocol paper, no results are presented. The planned sample size of 90 is relatively small for a smoking cessation trial. Enrolling only overweight/prediabetic smokers limits generalizability to all smokers. Exenatide is an older GLP-1 RA with less potent effects than newer agents like semaglutide, so the results may underestimate the potential of the drug class. The 4-week post-treatment follow-up is short for assessing sustained abstinence.
How to read the evidence
This is a study protocol describing a planned randomized controlled trial. No results are included. The trial design (double-blind, placebo-controlled, with biochemical verification of abstinence) is rigorous, but the evidence is prospective — the actual findings have not yet been reported in this paper.
When this study was published
Published in 2018, this protocol predates the recent surge of interest in GLP-1 drugs for addiction. It was prescient in proposing this application. Results from this or similar trials would now be of extremely high interest given the growing evidence linking GLP-1 agonists to reduced addictive behaviors.
The bigger picture
This 2018 protocol was ahead of its time. In the years since, the discovery that GLP-1 drugs reduce alcohol consumption and potentially other addictive behaviors has become one of the hottest topics in addiction medicine. Exenatide (derived from Gila monster venom peptide exendin-4) was the first GLP-1 RA to reach market, and this trial represents one of the earliest formal attempts to test the addiction-reducing hypothesis in humans. The concept has since expanded to include alcohol, opioids, and other substances.
Questions still open
- Would newer, more potent GLP-1 agonists like semaglutide show even stronger effects on smoking cessation than exenatide?
- Does the smoking cessation effect of GLP-1 drugs depend on their metabolic/weight loss effects, or is it mediated through independent brain reward pathways?
- Could GLP-1 drugs be combined with existing cessation medications (varenicline, bupropion) for even greater efficacy?
Common questions
Why would a diabetes drug help people quit smoking?
Did the trial show that exenatide helps with quitting smoking?
Read the original research
Exenatide once weekly for smoking cessation: study protocol for a randomized clinical trial.
Medicine, 97(2), e9567
Citation
Yammine, Luba; Kosten, Thomas R; Cinciripini, Paul M; Green, Charles E; Meininger, Janet C; Minnix, Jennifer A; Newton, Thomas F. (2018). Exenatide once weekly for smoking cessation: study protocol for a randomized clinical trial.. Medicine, 97(2), e9567. https://doi.org/10.1097/MD.0000000000009567