Louis A. Faillace, M.D., Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School, Houston, TX, USA.
Department of Pediatrics, Center for Clinical Research and Evidence-Based Medicine, UTHealth, McGovern Medical School, Houston, TX, USA.
Nicotine Tob Res. 2021 Aug 29;23(10):1682-1690. doi: 10.1093/ntr/ntab066.
Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving, and withdrawal symptoms, with post-cessation body weight as a secondary outcome.
Eighty-four prediabetic and/or overweight smokers were randomized (1 : 1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal, and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes.
Exenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (risk ratio [RR] = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP = 97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively.
Exenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies.
Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.
已批准的戒烟药理学治疗方法效果有限，这突显了需要改进的药理学治疗方法。胰高血糖素样肽-1 受体 (GLP-1R) 激动剂可在临床前研究中减轻尼古丁的奖赏作用。我们研究了长效艾塞那肽（一种 GLP-1R 激动剂）与尼古丁替代疗法（贴片）联合用于戒烟、渴望和戒断症状的疗效，以戒烟后的体重为次要结局。
84 名糖尿病前期和/或超重吸烟者被随机（1：1）接受每周一次安慰剂或皮下注射 2 毫克艾塞那肽。所有参与者均接受尼古丁替代疗法（21 毫克）和简短的戒烟咨询。治疗 6 周后评估 7 天点患病率（呼出 CO 水平≤5 ppm）、渴望、戒断和戒烟后的体重。广义线性模型的贝叶斯分析方法得出了后验概率（PP），以量化治疗对研究结果的假设效果的证据。
与安慰剂相比，艾塞那肽增加了戒烟的风险（分别为 46.3%和 26.8%），（风险比 [RR] = 1.70；95%置信区间 [0.96，3.27]；PP = 96.5%）。艾塞那肽降低了总体样本中的治疗结束时的渴望和戒烟者中的戒断症状。与安慰剂相比，艾塞那肽组的戒烟后体重降低了 5.6 磅（PP = 97.4%）。艾塞那肽组和安慰剂组分别有 9.5%和 2.3%的参与者报告了不良事件。
与尼古丁替代疗法联合使用艾塞那肽可提高戒烟率，降低渴望和戒断症状，并减轻戒烟者的体重增加。这些发现表明，GLP-1R 激动剂策略值得在更大、更长期的研究中进一步研究。
尽管在烟草控制方面取得了相当大的进展，但吸烟仍是可预防疾病、残疾和死亡的主要原因。在这项初步研究中，我们发现长效艾塞那肽，一种胰高血糖素样肽-1 受体激动剂，与尼古丁贴片联合使用可提高戒烟率，并减轻戒烟后的体重增加，与单独使用贴片相比。还需要进一步的研究来证实这些初步的积极结果。
