Summary: Semaglutide shows promise in helping patients with type 2 diabetes quit smoking. A study found it reduced tobacco use disorder-related medical visits and the need for smoking cessation medications. By targeting GLP-1 receptors, semaglutide may reduce nicotine addiction without causing fatigue or weight gain, offering potential benefits for managing both diabetes and smoking.
Smoking cessation remains a significant challenge, and the health effects are much worse for those who also have type 2 diabetes mellitus (T2DM). An article from the Annals of Internal Medicine have highlighted the potential of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in aiding smoking cessation. This article explores these findings and delves into the role of GLP-1 receptors in nicotine addiction, offering insights valuable for both healthcare providers and patients.
Understanding the Challenge
Patients with T2DM who smoke face increased health risks, including cardiovascular complications and poor glycemic control than either the diabetes or smoking in isolation. The magnitude of effect is a multiplier rather than additive in nature.Traditional smoking cessation methods often have limited success rates in this population, necessitating alternative approaches.
Semaglutide’s Impact on Tobacco Use Disorder
Study Design and Participants
A pivotal study by Wang et al. (2024) investigated the association of semaglutide with tobacco use disorder (TUD) in patients with T2DM. Utilizing a target trial emulation, the researchers compared semaglutide with seven other antidiabetic medications, including metformin. Data were sourced from a nationwide, population-based database of electronic health records (EHRs) in the U.S., covering patients from December 2017 to March 2023.
The analysis involved 222,942 patients with comorbid T2DM and TUD, including 5,967 new users of semaglutide. Comparisons were made with new users of insulin, metformin, dipeptidyl-peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, thiazolidinediones, and other GLP-1RAs.
Key Findings
- Reduced TUD-Related Encounters: Semaglutide significantly reduced the risk of medical encounters related to TUD and smoking cessation measures.
- Comparative Effectiveness: The strongest effect was observed when comparing semaglutide to insulin (hazard ratio [HR] 0.68), with a smaller yet statistically significant effect compared to metformin (HR 0.82).
- Decrease in Smoking Cessation Interventions: Patients on semaglutide required fewer smoking cessation medication prescriptions and counseling sessions.
Clinical Significance
These findings suggest that semaglutide not only manages blood glucose levels but may also aid in reducing nicotine dependence. This dual benefit is particularly advantageous for patients struggling with both T2DM and TUD.
The Role of GLP-1 Receptors in Nicotine Addiction
Insights from Animal Studies
Research by Eren-Yazicioglu et al. (2021) delved into how manipulating GLP-1 receptors can impact nicotine addiction:One of the best ways to elucidate the function of a particular protein or receptor is to see what happens when it is removed and observe the deficit in an animal model such as a mouse. Researchers can purchase knockout mice with a specific missing gene..
- Knockout Mice Studies: Knockout mice that are lacking the GLP-1 receptor (GLP-1R) that were given Ex-4 showed increased nicotine intake compared to the regular mice, indicating the receptor’s role in limiting addiction.
- Effect of GLP-1R Agonists: Substances like exendin-4 (Ex-4) and sitagliptin reduced nicotine intake in mice without causing fatigue or affecting normal food intake. This is important because it ensures the mice were truly less addicted to being too tired to self-administer the nicotine.
- Brain Pathways: The study identified that GLP-1 neurons in the nucleus tractus solitarius (NTS) project to the interpeduncular nucleus (IPN), influencing nicotine intake without affecting appetite.
Fatigue Considerations and Weight Gain
Treatments with GLP1-RA resulting in decreased nicotine intake did not induce fatigue or malaise in the mice. The lack of fatigue from administering GLP1-RA is essential because researchers can be confident that the lack of nicotine self-administration by mice was due to the resolution of chemical addiction in the brain rather than physically being too tired to administer the nicotine.
When an adult quits cigarettes and or other nicotine products, there is an average of 4-5kg weight gain. Experiments on mice showed that GLP1-RA can allow for nicotine cessation without weight gain.
Given that GLP-1RA does not cause fatigue and prevent rebound weight gain during nicotine cessation, it is an excellent candidate for pharmacological assistance for smoking cessation. Although a clinical trial is required to confirm the efficacy of nicotine cessation, the mouse studies and large-scale human observational studies already provide compelling evidence that physicians should strongly consider an off-label addition to existing pharmacologic interventions for smoking cessation.
Disclaimer: This article is for informational purposes only and does not substitute professional medical advice. Always consult a qualified healthcare provider for guidance tailored to your health situation.
At CanadianInsulin, we’re dedicated to providing up-to-date information and quality medications to support your health needs. Explore our range of GLP-1 receptor agonists and consult with our pharmacists for more information.
