CoChat
Sign Up
Cited by 20Smoking Behavior and CessationPharmacology and Obesity TreatmentSubstance Abuse Treatment and Outcomes

Glucagon-like peptide-1 analogues: a new way to quit smoking? (SKIP)—a structured summary of a study protocol for a randomized controlled study

Open access
Lengsfeld, Sophia, Burkard, Thilo, Meienberg, Andrea, Jeanloz, Nica, Coynel, David, Vogt, Deborah R., Hemkens, Lars G., Speich, Benjamin +4 more·2023·Trials
DOI 10.1186/s13063-023-07164-9PMC PMC10120253
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Cigarette smoking is the leading preventable cause of premature death. Despite dedicated programmes, quit rates remain low due to barriers such as nicotine withdrawal syndrome or post-cessation weight gain. Glucagon-like peptide-1 (GLP-1) analogues reduce energy intake and body weight and seem to modulate addictive behaviour. These GLP-1 properties are of major interest in the context of smoking cessation. The aim of this study is to evaluate the GLP-1 analogue dulaglutide as a new therapy for smoking cessation. Methods: This is a placebo-controlled, double-blind, parallel group, superiority, single-centre randomized study including 255 patients. The intervention consists of a 12-week dulaglutide treatment phase with 1.5 mg once weekly or placebo subcutaneously, in addition to standard of care (behavioural counselling and pharmacotherapy with varenicline). A 40-week non-treatment phase follows. The primary outcome is the point prevalence abstinence rate at week 12. Smoking status is self-reported and biochemically confirmed by end-expiratory exhaled carbon monoxide measurement. Further endpoints include post-cessational weight gain, nicotine craving analysis, glucose homeostasis and long-term nicotine abstinence. Two separate substudies assess behavioural, functional and structural changes by functional magnetic resonance imaging and measures of energy metabolism (i.e. resting energy expenditure, body composition). Discussion: Combining behavioural counselling and medical therapy, e.g. with varenicline, improves abstinence rates and is considered the standard of care. We expect a further increase in quit rates by adding a second component of medical therapy and assume a dual effect of dulaglutide treatment (blunting nicotine withdrawal symptoms and reducing post-cessational weight gain). This project is of high relevance as it explores novel treatment options aimed at preventing the disastrous consequences of nicotine consumption and obesity. Trial registration: ClinicalTrials.gov NCT03204396. Registered on June 26, 2017.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s13063-023-07164-9

Cites

12 of 12 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Nicotine influences the central nervous system by modulating appetite-regulating peptides such as GLP-1 and hypocretin-1, which play crucial roles in hunger and satiety signals.

    “Furthermore, nicotine also influences the central nervous system by modulating appetite-regulating peptides such as glucagon-like peptide- 1 (GLP-1) and hypocretin-1, which play crucial roles in hunger and satiety signals [21, 22].”

    From Smoking and its impact on eating behavior: A review (2026) · cites this paper as [21]

    The Introduction, Background and rationale (page not specified), describes GLP-1 as involved in appetite and satiation and says preclinical studies suggest nicotine activates GLP-1 neurons. It does not discuss hypocretin-1 or show that nicotine modulates both named peptides in hunger and satiety signaling; the nicotine–GLP-1 evidence is also qualified as preclinical. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Smokers may use smoking instead of eating to cope with stress, leading to decreased food intake and body weight; after smoking cessation, these individuals may be more susceptible to weight gain when eating is used to cope with stress.

    “Literature has shown that smokers may use smoking instead of eating to cope with stress, leading to decreased food intake and body weight. However, after smoking cessation, these individuals may be more susceptible to weight gain when eating is used to cope with stress (Stress eating) [21].”

    From Smoking and its impact on eating behavior: A review (2026) · cites this paper as [21]

    The Introduction (Background and rationale; page not provided) reports that people who quit smoking gain an average of 4–5 kg within 12 months. It does not say that smokers use cigarettes instead of food to cope with stress, that this decreases food intake or weight, or that stress eating explains weight gain after cessation. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 40

  1. [1]Chan AW Tetzlaff JM Gøtzsche PC Altman DG Mann H Berlin JA SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials BMJ 2013 346 e7586 10.1136/bmj.e7586 23303884 PMC3541470 · DOI · Paper page
  2. [2]Jha P Ramasundarahettige C Landsman V Rostron B Thun M Anderson RN 21st-century hazards of smoking and benefits of cessation in the United States N Engl J Med 2013 368 4 341 350 10.1056/NEJMsa1211128 23343063 · DOI · Paper page
  3. [3]Rigotti NA Strategies to help a smoker who is struggling to quit JAMA 2012 308 15 1573 1580 10.1001/jama.2012.13043 23073954 PMC4562427 · DOI
  4. [5]Stead LF Koilpillai P Fanshawe TR Lancaster T Combined pharmacotherapy and behavioural interventions for smoking cessation Cochrane Database Syst Rev 2016 3 Cd008286 27009521 PMC10042551
  5. [7]Henningfield JE Miyasato K Jasinski DR Abuse liability and pharmacodynamic characteristics of intravenous and inhaled nicotine J Pharmacol Exp Ther 1985 234 1 1 12 4009494
  6. [8]Siahpush M Singh GK Tibbits M Pinard CA Shaikh RA Yaroch A It is better to be a fat ex-smoker than a thin smoker: findings from the 1997–2004 National Health Interview Survey-National Death Index linkage study Tob Control 2014 23 5 395 402 10.1136/tobaccocontrol-2012-050912 23574644 · DOI
  7. [9]Tian J Venn A Otahal P Gall S The association between quitting smoking and weight gain: a systematic review and meta-analysis of prospective cohort studies Obes Rev 2015 16 10 883 901 10.1111/obr.12304 26114839 · DOI
  8. [10]O'Hara P Connett JE Lee WW Nides M Murray R Wise R Early and late weight gain following smoking cessation in the Lung Health Study Am J Epidemiol 1998 148 9 821 830 10.1093/oxfordjournals.aje.a009706 9801011 · DOI
  9. [12]Yeh HC Duncan BB Schmidt MI Wang NY Brancati FL Smoking, smoking cessation, and risk for type 2 diabetes mellitus: a cohort study Ann Intern Med 2010 152 1 10 17 10.7326/0003-4819-152-1-201001050-00005 20048267 PMC5726255 · DOI
  10. [13]Harris KK Zopey M Friedman TC Metabolic effects of smoking cessation Nat Rev Endocrinol 2016 12 5 299 308 10.1038/nrendo.2016.32 26939981 PMC5021526 · DOI
  11. [14]Hu Y Zong G Liu G Wang M Rosner B Pan A Smoking cessation, weight change, type 2 diabetes, and mortality N Engl J Med 2018 379 7 623 632 10.1056/NEJMoa1803626 30110591 PMC6165582 · DOI
  12. [15]Aubin HJ Farley A Lycett D Lahmek P Aveyard P Weight gain in smokers after quitting cigarettes: meta-analysis BMJ 2012 345 e4439 10.1136/bmj.e4439 22782848 PMC3393785 · DOI · Paper page
  13. [16]Parsons AC Shraim M Inglis J Aveyard P Hajek P Interventions for preventing weight gain after smoking cessation Cochrane Database Syst Rev 2009 1 Cd006219 19160269
  14. [17]Herrmann C Göke R Richter G Fehmann HC Arnold R Göke B Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients Digestion 1995 56 2 117 126 10.1159/000201231 7750665 · DOI · Paper page
  15. [18]Gutniak M Orskov C Holst JJ Ahrén B Efendic S Antidiabetogenic effect of glucagon-like peptide-1 (7–36)amide in normal subjects and patients with diabetes mellitus N Engl J Med 1992 326 20 1316 1322 10.1056/NEJM199205143262003 1348845 · DOI · Paper page
  16. [21]Merchenthaler I Lane M Shughrue P Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system J Comp Neurol 1999 403 2 261 280 10.1002/(SICI)1096-9861(19990111)403:2<261::AID-CNE8>3.0.CO;2-5 9886047 · DOI
  17. [22]Alvarez E Roncero I Chowen JA Thorens B Blázquez E Expression of the glucagon-like peptide-1 receptor gene in rat brain J Neurochem 1996 66 3 920 927 10.1046/j.1471-4159.1996.66030920.x 8769850 · DOI · Paper page
  18. [24]Engel JA Jerlhag E Role of appetite-regulating peptides in the pathophysiology of addiction: implications for pharmacotherapy CNS Drugs 2014 28 10 875 886 10.1007/s40263-014-0178-y 24958205 PMC4181507 · DOI
  19. [25]Morganstern I Barson JR Leibowitz SF Regulation of drug and palatable food overconsumption by similar peptide systems Curr Drug Abuse Rev 2011 4 3 163 173 10.2174/1874473711104030163 21999690 PMC6713271 · DOI
  20. [26]Yammine L Kosten TR Pimenova M Schmitz JM Cigarette smoking, type 2 diabetes mellitus, and glucagon-like peptide-1 receptor agonists as a potential treatment for smokers with diabetes: an integrative review Diabetes Res Clin Pract 2019 149 78 88 10.1016/j.diabres.2019.01.033 30735771 · DOI
  21. [28]Egecioglu E Engel JA Jerlhag E 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 PLoS ONE 2013 8 10 e77284 10.1371/journal.pone.0077284 24204788 PMC3799694 · DOI · Paper page
  22. [29]Yammine L Green CE Kosten TR de Dios C Suchting R Lane SD Exenatide adjunct to nicotine patch facilitates smoking cessation and may reduce post-cessation weight gain: a pilot randomized controlled trial Nicotine Tob Res 2021 23 10 1682 1690 10.1093/ntr/ntab066 33831213 PMC8517504 · DOI
  23. [30]Heatherton TF Kozlowski LT Frecker RC Fagerström KO The Fagerström test for nicotine dependence: a revision of the Fagerström Tolerance Questionnaire Br J Addict 1991 86 9 1119 1127 10.1111/j.1360-0443.1991.tb01879.x 1932883 · DOI · Paper page
  24. [31]Fagerstrom K Determinants of tobacco use and renaming the FTND to the Fagerstrom test for cigarette dependence Nicotine Tob Res 2012 14 1 75 78 10.1093/ntr/ntr137 22025545 · DOI
  25. [33]Kalinowski A Humphreys K Governmental standard drink definitions and low-risk alcohol consumption guidelines in 37 countries Addiction 2016 111 7 1293 1298 10.1111/add.13341 27073140 · DOI
  26. [35]Umpierrez G Tofe Povedano S Perez Manghi F Shurzinske L Pechtner V Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3) Diabetes Care 2014 37 8 2168 2176 10.2337/dc13-2759 24842985 · DOI · Paper page
  27. [37]Dungan KM Povedano ST Forst T González JG Atisso C Sealls W Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial Lancet 2014 384 9951 1349 1357 10.1016/S0140-6736(14)60976-4 25018121 · DOI · Paper page
  28. [40]Müller V Mucha R Ackermann K Pauli P Die Erfassung des Cravings bei Rauchern mit einer deutschen Version des "Questionnaire on SMoking Urges" (QSU-G) Z Klin Psychol Psychother 2001 30 3 164 171 10.1026/0084-5345.30.3.164 · DOI
  29. [43]Brody AL Mandelkern MA Olmstead RE Jou J Tiongson E Allen V Neural substrates of resisting craving during cigarette cue exposure Biol Psychiatry 2007 62 6 642 651 10.1016/j.biopsych.2006.10.026 17217932 PMC1992815 · DOI
  30. [44]Broome MR Matthiasson P Fusar-Poli P Woolley JB Johns LC Tabraham P Neural correlates of executive function and working memory in the 'at-risk mental state' Br J Psychiatry 2009 194 1 25 33 10.1192/bjp.bp.107.046789 19118321 · DOI
  31. [45]Ettinger U Williams SC Fannon D Premkumar P Kuipers E Moller HJ Functional magnetic resonance imaging of a parametric working memory task in schizophrenia: relationship with performance and effects of antipsychotic treatment Psychopharmacology 2011 216 1 17 27 10.1007/s00213-011-2214-7 21331519 PMC3111549 · DOI
  32. [46]Reichmann F Holzer P Neuropeptide Y: A stressful review Neuropeptides 2016 55 99 109 10.1016/j.npep.2015.09.008 26441327 PMC4830398 · DOI · Paper page
  33. [48]Jackson D White IR Mason D Sutton S A general method for handling missing binary outcome data in randomized controlled trials Addiction 2014 109 12 1986 1993 10.1111/add.12721 25171441 PMC4241048 · DOI
  34. [50]ICH Expert Working Group. International Conference on Harmonisation of Technical Requirements for Registration og Pharmaceuticals for Human Use (ICH) harmonised Tripartite Guideline Clinical Safety Data Management: Definitions and Standards for Expedited Reporting. https://database.ich.org/sites/default/files/E2A_Guideline.pdf.
  35. [51]Hayes MR Schmidt HD GLP-1 influences food and drug reward Curr Opin Behav Sci 2016 9 66 70 10.1016/j.cobeha.2016.02.005 27066524 PMC4822543 · DOI · Paper page
  36. [52]Jerlhag E GLP-1 signaling and alcohol-mediated behaviors; preclinical and clinical evidence Neuropharmacology 2018 136 Pt B 343 349 10.1016/j.neuropharm.2018.01.013 29337226 · DOI · Paper page
  37. [53]Antonsen KK Klausen MK Brunchmann AS le Dous N Jensen ME Miskowiak KW Does glucagon-like peptide-1 (GLP-1) receptor agonist stimulation reduce alcohol intake in patients with alcohol dependence: study protocol of a randomised, double-blinded, placebo-controlled clinical trial BMJ Open 2018 8 7 e019562 10.1136/bmjopen-2017-019562 30012779 PMC6082448 · DOI
  38. [55]Anthenelli RM Benowitz NL West R St Aubin L McRae T Lawrence D Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial Lancet 2016 387 10037 2507 2520 10.1016/S0140-6736(16)30272-0 27116918 · DOI · Paper page
  39. [56]Chang PH Chiang CH Ho WC Wu PZ Tsai JS Guo FR Combination therapy of varenicline with nicotine replacement therapy is better than varenicline alone: a systematic review and meta-analysis of randomized controlled trials BMC Public Health 2015 15 689 10.1186/s12889-015-2055-0 26198192 PMC4508997 · DOI · Paper page
  40. [57]Schwartz D Lellouch J Explanatory and pragmatic attitudes in therapeutical trials J Chronic Dis 1967 20 8 637 648 10.1016/0021-9681(67)90041-0 4860352 · DOI · Paper page

Cited by

Sorted by citations

Authors
Lengsfeld, S., Burkard, T., Meienberg, A., Jeanloz, N., Coynel, D., Vogt, D. R., Hemkens, L. G., Speich, B., Zanchi, D., Erlanger, T. E., Christ-Crain, M., & Winzeler, B.
Affiliations
  • University Hospital of Basel (CH)
  • University of Basel (CH)
  • F. Hoffmann-La Roche AG (CH)
Corresponding author
Winzeler, Bettina
ORCID
Venue
Trials
Publisher
Springer Science and Business Media LLC
Published
2023-04-20
Volume
24
Issue
1
Pages
284-284
ISSN
1745-6215 (ISSN-L)
DOI
10.1186/s13063-023-07164-9
PMC
PMC10120253
OpenAlex
W4366595992
Cited by
20
References
12
Citations by year
2026: 5 · 2025: 7 · 2024: 6 · 2023: 2
FWCI
3.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Trials (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • The University Hospital Basel (and the integrated Clinical Trial Unit and Department of Endocrinology, Diabetology and Metabolism) provide the location and infrastructure.
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • goldschmidt&Jakobson Stiftung
  • University Hospital Basel, Pool Medizin im Jahr 2021
  • Gottfried und Julia Bangerter-Rhyner-Stiftung
  • Hemmi Foundation
  • Department of Internal Medicine of the University Hospital of Basel
  • Swiss Academy of Medical Sciences
  • Research Foundation of the University of Basel
  • University of Basel
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
smoking cessation, dulaglutide, GLP-1 receptor agonists, nicotine withdrawal, post-cessation weight gain, nicotine craving, glucose homeostasis, varenicline, exhaled carbon monoxide, resting energy expenditure, body composition, obesity
MeSH terms
Varenicline, Equivalence Trials as Topic, Double-Blind Method, Humans, Nicotine, Substance Withdrawal Syndrome, Weight Gain, Randomized Controlled Trials as Topic, Smoking Cessation, Glucagon-Like Peptide 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review