CHANGES IN SMOKING-RELATED OUTCOMES WITH TIRZEPATIDE IN INDIVIDUALS WITH METHAMPHETAMINE USE DISORDER WHO SMOKE

Background

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as novel candidate drugs for treating a range of substance use disorders. In a recent systematic review, we found 9 trials that were registered in clinicaltrials.gov to evaluate smoking-related outcomes in individuals with tobacco use disorder. Furthermore, only two prior reports have evaluated the efficacy of GLP-1RAs along with additional smoking cessation treatments (Yammine et al. 2021 and Lengsfeld et al. 2023) and neither found significant medication effects for reducing smoking. However, the effects of these medications on smoking outcomes in the context of another substance use disorder remains poorly understood. In a recent report, Hendershot et al. found that semaglutide, a GLP-1RA administered once weekly as subcutaneous injection, resulted in greater reduction in cigarettes smoked per day as compared to placebo in individuals with moderate-to-severe alcohol use disorder. However, effects of tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist on smoking-related outcomes remain poorly understood. Here, we present changes in smoking-related outcomes rom the first study of tirzepatide in individuals with methamphetamine use disorder (MtUD).

Methods

Participants with moderate-to-severe MtUD who received 32 weeks of treatment with tirzepatide (administered weekly, per prescribing label) for a weight-related indication were included (NCT06745128). Number of cigarettes smoked per day (CPD) was obtained for 30 days preceding informed consent at baseline, and for each day of study participation using the timeline followback (TLFB) procedure. Additionally, worst craving for nicotine in the past week was assessed using a visual analog scale (VAS) at baseline (pre-first dose of tirzepatide), and at weekly interval for 32 weeks. Repeated measures mixed model analyses were used to measure changes in CPD and VAS.

Results

Of 35 individuals enrolled, 20 reported smoking cigarettes [14 females/6 males; mean (standard deviation, SD) age = 46.7 (7.1) years]. At baseline, mean (SD) values of CPD and VAS were 11.7 (6.0) and 77.4 (23.8), respectively. After 32 weeks of treatment with tirzepatide, there were significant reductions in CPD [estimate(β)= -2.76, standard error (SE)= 0.56, p < 0.0001] and VAS for nicotine (β= -25.1, SE= 4.99, p < 0.0001).

Conclusions

This first study of a GLP-1RA in individuals with MtUD who smoke found preliminary evidence for significant reduction in smoking-related outcomes, including numbers of cigarettes smoke and craving symptoms. Larger placebo-controlled randomized controlled trials are needed to validate these findings.