{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T19:58:34Z","timestamp":1779047914598,"version":"3.51.4"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"UTHealth Center for Clinical and Translational Sciences"},{"name":"CTSA Scholar Award"},{"name":"PARTNERS Research Awards"},{"name":"Quinn Oncology Research Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Understanding predictors of smoking cessation medication efficacy facilitates the ability to enhance treatment effectiveness. In our pilot trial, exenatide, a glucagon-like peptide-1 receptor agonist, adjunct to nicotine patch improved smoking abstinence compared to nicotine patch alone. This secondary analysis explores potential baseline characteristics associated with differential treatment response to exenatide.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aims and Methods<\/jats:title>\n                  <jats:p>The parent trial randomized (1:1) 84 smokers with prediabetes and\/or overweight to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received nicotine patch (21 mg) and brief smoking cessation counseling, with biologically confirmed 7-day point prevalence abstinence at week 6 (end-of-treatment) deemed the primary outcome. Bayesian generalized linear modeling explored differential response to treatment as a function of baseline patient characteristics, including demographic, psychosocial, clinical, smoking-related, and genetic factors. Posterior probability (PP) \u2265 75% that an effect exists was taken as a minimum threshold of evidence in favor of model effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Exenatide showed stronger benefit versus placebo in participants who smoked &amp;gt;20 cigarettes per day (PP = 81.7%) and in those without prediabetes (PP = 76.0%) or obesity (PP = 94.4%). Exenatide\u2019s efficacy was observed only in individuals with no\/minimal depression symptoms but not in those with symptoms (PP = 91.2%). Finally, exenatide was more efficacious than placebo only in those with the CHRNA rs16969968 GG genotype (PP = 88.6%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The effect of exenatide on abstinence may be moderated by the number of cigarettes smoked daily, metabolic, psychological, and genetic factors. Larger prospective investigations are needed to confirm and extend these findings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications<\/jats:title>\n                  <jats:p>Understanding predictors of smoking cessation medication efficacy enhances the ability to improve treatment effectiveness. In our pilot trial, extended-release exenatide, a GLP-1 receptor agonist, adjunct to nicotine patch, improved smoking abstinence in smokers with prediabetes and\/or overweight. The current post-hoc analysis found that the effect of exenatide on smoking abstinence may be moderated by the number of cigarettes smoked daily, metabolic, psychological, and genetic factors. Larger investigations are needed to confirm and extend these findings.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ntr\/ntaf005","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T06:01:26Z","timestamp":1736402486000},"page":"1294-1300","source":"Crossref","is-referenced-by-count":12,"title":["Exploring Predictors of Treatment Response to GLP-1 Receptor Agonists for Smoking Cessation"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-8802","authenticated-orcid":false,"given":"Luba","family":"Yammine","sequence":"first","affiliation":[{"name":"Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0230-5222","authenticated-orcid":false,"given":"Constanza","family":"de Dios","sequence":"additional","affiliation":[{"name":"Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-3754","authenticated-orcid":false,"given":"Robert","family":"Suchting","sequence":"additional","affiliation":[{"name":"Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles E","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Clinical Research and Evidence-Based Medicine, UTHealth, McGovern Medical School , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2583-0233","authenticated-orcid":false,"given":"David A","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine , Houston, TX ,","place":["USA"]},{"name":"Department of Pharmacology and Chemical Biology, Baylor College of Medicine , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Consuelo","family":"Walss-Bass","sequence":"additional","affiliation":[{"name":"Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy M","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"2025070211164976600_CIT0001","author":"U.S. Department of Health and Human Services","journal-title":"Smoking Cessation: a Report of the Surgeon General 2020"},{"issue":"5","key":"2025070211164976600_CIT0002","first-page":"CD009329","article-title":"Pharmacological interventions for smoking cessation: an overview and network meta-analysis","volume":"2013","author":"Cahill","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"issue":"10","key":"2025070211164976600_CIT0003","doi-asserted-by":"crossref","first-page":"e77284","DOI":"10.1371\/journal.pone.0077284","article-title":"The glucagon-like peptide 1 analogue Exendin-4 attenuates the nicotine-induced locomotor stimulation, accumbal dopamine release, conditioned place preference as well as the expression of locomotor sensitization in mice","volume":"8","author":"Egecioglu","year":"2013","journal-title":"PLoS One."},{"issue":"5","key":"2025070211164976600_CIT0004","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/nn.4540","article-title":"GLP-1 acts on habenular avoidance circuits to control nicotine intake","volume":"20","author":"Tuesta","year":"2017","journal-title":"Nat Neurosci."},{"issue":"10","key":"2025070211164976600_CIT0005","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1093\/ntr\/ntab066","article-title":"Exenatide adjunct to nicotine patch facilitates smoking cessation and may reduce post-cessation weight gain: a pilot randomized controlled trial","volume":"23","author":"Yammine","year":"2021","journal-title":"Nicotine Tob Res"},{"key":"2025070211164976600_CIT0006","doi-asserted-by":"crossref","first-page":"101865","DOI":"10.1016\/j.eclinm.2023.101865","article-title":"Effect of dulaglutide in promoting abstinence during smoking cessation: a single-centre, randomized, double-blind, placebo-controlled, parallel group trial","volume":"57","author":"Lengsfeld","year":"2023","journal-title":"EClinicalMedicine"},{"issue":"12","key":"2025070211164976600_CIT0007","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1038\/s41591-023-02634-8","article-title":"GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders","volume":"29","author":"Leggio","year":"2023","journal-title":"Nat Med."},{"issue":"8","key":"2025070211164976600_CIT0008","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1111\/add.14208","article-title":"Factors associated with the efficacy of smoking cessation treatments and predictors of smoking abstinence in EAGLES","volume":"113","author":"West","year":"2018","journal-title":"Addiction."},{"issue":"6","key":"2025070211164976600_CIT0009","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1002\/cpt.1971","article-title":"Genetic variant in CHRNA5 and response to varenicline and combination nicotine replacement in a randomized placebo-controlled trial","volume":"108","author":"Chen","year":"2020","journal-title":"Clin Pharmacol Ther."},{"key":"2025070211164976600_CIT0010","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.drugalcdep.2015.06.022","article-title":"Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation","volume":"154","author":"Chen","year":"2015","journal-title":"Drug Alcohol Depend."},{"issue":"9","key":"2025070211164976600_CIT0011","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1111\/j.1360-0443.1991.tb01879.x","article-title":"The fagerstrom test for nicotine dependence: a revision of the fagerstrom tolerance questionnaire","volume":"86","author":"Heatherton","year":"1991","journal-title":"Br J Addict."},{"issue":"1-3","key":"2025070211164976600_CIT0012","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.jad.2008.06.026","article-title":"The PHQ-8 as a measure of current depression in the general population","volume":"114","author":"Kroenke","year":"2009","journal-title":"J Affect Disord."},{"key":"2025070211164976600_CIT0013","volume-title":"A Language and Environment for Statistical Computing","author":"R Development Core Team","year":"2023"},{"key":"2025070211164976600_CIT0014","first-page":"28","article-title":"brms: an R package for bayesian multilevel models using Stan","volume-title":"J Stat Software.","author":"B\u00fcrkner","year":"2017"},{"issue":"19","key":"2025070211164976600_CIT0015","doi-asserted-by":"crossref","first-page":"e159863","DOI":"10.1172\/jci.insight.159863","article-title":"Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial","volume":"7","author":"Klausen","year":"2022","journal-title":"JCI Insight"},{"issue":"1","key":"2025070211164976600_CIT0016","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/jdi.12543","article-title":"Varenicline in smokers with diabetes: a pooled analysis of 15 randomized, placebo-controlled studies of varenicline","volume":"8","author":"Tonstad","year":"2017","journal-title":"J Diabetes Invest"},{"issue":"1","key":"2025070211164976600_CIT0017","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1370\/afm.36","article-title":"Diabetic patients who smoke: are they different","volume":"2","author":"Solberg","year":"2004","journal-title":"Ann Fam Med."},{"issue":"3","key":"2025070211164976600_CIT0018","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/s12160-016-9869-6","article-title":"Depression and smoking cessation: evidence from a smoking cessation clinic with 1-year follow-up","volume":"51","author":"Stepankova","year":"2016","journal-title":"Ann Behav Med."},{"issue":"4","key":"2025070211164976600_CIT0019","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1007\/s43440-021-00274-8","article-title":"Insights into a possible role of glucagon-like peptide-1 receptor agonists in the treatment of depression","volume":"73","author":"Detka","year":"2021","journal-title":"Pharmacol Rep."},{"issue":"9","key":"2025070211164976600_CIT0020","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.jacc.2024.06.001","article-title":"Efficacy of semaglutide by sex in obesity-related heart failure with preserved ejection fraction: STEP-HFpEF trials","volume":"84","author":"Verma","year":"2024","journal-title":"J Am Coll Cardiol."}],"container-title":["Nicotine and Tobacco Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ntr\/advance-article-pdf\/doi\/10.1093\/ntr\/ntaf005\/61382773\/ntaf005.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ntr\/article-pdf\/27\/7\/1294\/61382773\/ntaf005.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ntr\/article-pdf\/27\/7\/1294\/61382773\/ntaf005.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T15:17:02Z","timestamp":1751469422000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ntr\/article\/27\/7\/1294\/7945832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":20,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,1,9]]},"published-print":{"date-parts":[[2025,6,23]]}},"URL":"https:\/\/doi.org\/10.1093\/ntr\/ntaf005","relation":{},"ISSN":["1469-994X"],"issn-type":[{"value":"1469-994X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,1,9]]}}}