GLP-1 receptor agonist indications and prescriptions among adults who do and do not smoke

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Leavens , View ORCID Profile Michael J. Arnold , View ORCID Profile Nicole L. Nollen , View ORCID Profile Lisa Sanderson Cox , View ORCID Profile Kristy A. Brown , View ORCID Profile Edward F. Ellerbeck doi: https://doi.org/10.1101/2025.08.12.25331941 Eleanor L.S. Leavens a Department of Population Health, University of Kansas Medical Center , Kansas City, KS, USA b University of Kansas Cancer Center , Kansas City, KS, USA PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Eleanor L.S. Leavens For correspondence: eleavens{at}kumc.edu Michael J. Arnold a Department of Population Health, University of Kansas Medical Center , Kansas City, KS, USA MPH Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Michael J. Arnold Nicole L. Nollen a Department of Population Health, University of Kansas Medical Center , Kansas City, KS, USA b University of Kansas Cancer Center , Kansas City, KS, USA PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Nicole L. Nollen Lisa Sanderson Cox a Department of Population Health, University of Kansas Medical Center , Kansas City, KS, USA b University of Kansas Cancer Center , Kansas City, KS, USA PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lisa Sanderson Cox Kristy A. Brown a Department of Population Health, University of Kansas Medical Center , Kansas City, KS, USA c Department of Cell Biology and Physiology, University of Kansas Medical Center , Kansas City, KS, USA PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kristy A. Brown Edward F. Ellerbeck a Department of Population Health, University of Kansas Medical Center , Kansas City, KS, USA b University of Kansas Cancer Center , Kansas City, KS, USA MD, MPH Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Edward F. Ellerbeck Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Background Smoking and obesity are leading causes of preventable morbidity and mortality, often co-occurring and synergistically increasing risks for cardiovascular disease and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for managing type 2 diabetes, obesity, and cardiovascular disease, and emerging evidence suggests potential benefit for smoking cessation. However, the prevalence of GLP-1 RA indications and prescriptions among adults who smoke is unknown. Objective To compare the frequency of GLP-1 RA indications and prescriptions among adults who do and do not smoke within a large Midwest health system. Methods Electronic health record data identified adults (≥18 years) with outpatient primary care visits from September 2023–2024. Patients were categorized as current smokers or non-smokers. We assessed indications for GLP-1 RAs—type 2 diabetes, weight management (BMI ≥30 or 27– 29.9 with comorbidity), and secondary prevention of cardiovascular disease and examined prescription rates among those with at least one indication. Results Of 59,981 patients, 4,843 (8.1%) were current smokers. Compared to non-smokers, adults who smoke were more likely to have an indication for GLP-1 RAs (66.1% vs. 62.6%; p <0.001) but less likely to receive a prescription (20.4% vs. 23.2%; p <0.001). This pattern was consistent across all indications. Conclusion Adults who smoke more frequently meet clinical criteria for GLP-1 RAs yet are less likely to be prescribed these therapies. Enhancing access to GLP-1 RAs for individuals who smoke could address critical metabolic and smoking-related health challenges, particularly given their potential role in supporting smoking cessation. BACKGROUND Smoking and obesity are the two leading causes of preventable death and disease in the United States. The two conditions, which often co-occur, are synergistically detrimental to health. 1 , 2 Individuals who smoke and have obesity are at greater risk for cardiovascular disease and diabetes, while also experiencing reduced quality of life and greater healthcare costs compared to individuals with either condition alone. 3 , 4 Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for the treatment of type 2 diabetes, obesity, and cardiovascular disease, but research on their use for comorbid smoking is in its infancy. A 6-week pilot study of exenatide added to nicotine patch 5 in adults with smoking and prediabetes and/or overweight reported a 46% abstinence rate - nearly double that of currently approved pharmacotherapy 5 — along with a 5.6 pound reduction in post-cessation body weight. GLP-1 RAs are the most promising advance for individuals with both tobacco use and obesity in over two decades, but the relative prevalence of indications for and uptake of GLP-1 RAs is unknown. OBJECTIVE This analysis of adults within a large Midwest health system compares the frequency of indications for GLP-1 RAs and GLP-1 RA prescriptions among adults who do and do not smoke. METHODS Data from a large, Midwest health system’s electronic health record (EHR) was used to identify adult patients ≥ 18 years of age receiving care in an outpatient primary care clinic between September 2023 to September 2024. From the overall sample, we identified the proportion identified in the EHR as being a current smoker versus non-current smoker. Within those two groups, we then identified patients with a current GLP-1 RA indication including for 1) the management of diabetes mellitus, 2) weight management (BMI ≥ 30.0 or BMI 27.0-29.9 with a weight-related comorbidity [i.e., hypertension, hyperlipidemia/hypercholesterolemia, obstructive sleep apnea, diabetes mellitus]), and 3) secondary prevention of cardiovascular disease (age 45+ with BMI of 27+ and history of myocardial infarction/stroke). Of those with at least one indication, we determined the proportion prescribed a GLP-1 RA including lixisenatide, exenatide, dulaglutide, liraglutide, semaglutide, or tirzepatide. RESULTS We identified 59,981 adult patients in primary care of whom 4,843 (8.1%) were current smokers. Adults who smoke were more likely to have an indication for a GLP-1 RA compared to non-smokers (66.1% vs 62.6%; p < 0.001) but were less likely than non-smokers to receive a GLP-1 RA (20.4% vs 23.2%; p < 0.001; Table 1 ). These findings were consistent across all indications for GLP-1 RAs, including diabetes, weight management, and cardiovascular disease prevention. View this table: View inline View popup Download powerpoint Table 1. Indications for and utilization of GLP-1 RA a among adults who do and do not smoke CONCLUSION Relative to non-smokers, adults who smoke were more likely to have an indication for a GLP-1 RA, but less likely to receive a prescription. This finding was consistent across all indications for GLP-1 RAs. There is an opportunity to increase utilization of GLP-1 RAs for weight and disease management, and in doing so, increase access to GLP-1 RAs among adults who smoke. When considering the well-established negative effects of smoking on metabolic health and the risk of weight gain post-cessation, GLP-1 RAs hold promise for simultaneously addressing critical metabolic and smoking-related health challenges in adults who smoke with an existing indication. Given the emerging data on GLP-1 RAs for smoking cessation, consideration should be given to integrating behavioral support for smoking cessation with the GLP-1 RA treatment. Data Availability Data are available upon reasonable request to the corresponding author. Funding The work was supported by the University of Kansas Cancer Center (P30CA168524) and T2025-007 (Brown) from the V Foundation for Cancer Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Role of the funder The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication References 1. ↵ Bush T , Levine MD , Deprey M , et al. Prevalence of weight concerns and obesity among smokers calling a quitline . Journal of smoking cessation . 2009 ; 4 ( 2 ): 74 – 78 . OpenUrl CrossRef 2. ↵ Chiolero A , Faeh D , Paccaud F , Cornus J. Consequences of smoking for body weight, body fat distribution, and insulin resistance . The American journal of clinical nutrition . 2008 ; 87 ( 4 ): 801 – 809 . OpenUrl Abstract / FREE Full Text 3. ↵ Mambo A , Yang Y , Mahulu E , Zihua Z. Investigating the interplay of smoking, cardiovascular risk factors, and overall cardiovascular disease risk: NHANES analysis 2011–2018 . BMC Cardiovascular Disorders . 2024 ; 24 ( 1 ): 193 . OpenUrl PubMed 4. ↵ Kim Y. The effects of smoking, alcohol consumption, obesity, and physical inactivity on healthcare costs: a longitudinal cohort study . BMC Public Health . 2025 ; 25 ( 1 ): 873 . OpenUrl PubMed 5. ↵ Yammine L , Green CE , Kosten TR , et al. Exenatide adjunct to nicotine patch facilitates smoking cessation and may reduce post-cessation weight gain: a pilot randomized controlled trial . Nicotine and Tobacco Research . 2021 ; 23 ( 10 ): 1682 – 1690 . OpenUrl PubMed View the discussion thread. Back to top Previous Next Posted August 17, 2025. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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