Naltrexone Hydrochloride

Semaglutide, tirzepatide, and other GLP-1 drugs appear to slow alcohol absorption and blunt its intoxicating effects, according to new research. The study found participants on these medications felt less drunk despite consuming the same amount of alcohol. This could point to a safer, faster-acting way to help people reduce drinking—distinct from traditional treatments that target the brain directly. Growing research suggests that medications commonly prescribed for diabetes and weight loss (including the well-known Ozempic and Wegovy) might also help people drink less alcohol. A new study from the Fralin Biomedical Research Institute at VTC, published this month in Scientific Reports, found that GLP-1 agonists appear to slow how quickly alcohol moves into the bloodstream, which in turn delays its effects on the brain. "People who drink know there's a difference between nursing a glass of wine and downing a shot of whiskey," said Alex DiFeliceantonio, assistant professor and interim co-director of the FBRI's Center for Health Behaviors Research. Although a standard serving of each contains the same amount of alcohol (0.6 ounces), a shot causes blood-alcohol levels to rise much faster. That quick spike feels stronger because of how the body absorbs and processes alcohol. "Why would this matter? Faster-acting drugs have a higher abuse potential," DiFeliceantonio said. "They have a different impact on the brain. So if GLP-1s slow alcohol entering the bloodstream, they could reduce the effects of alcohol and help people drink less." More than half of U.S. adults consume alcohol, and about one in ten has an alcohol use disorder. Chronic, heavy drinking is linked to conditions such as high blood pressure, heart and liver disease, and several cancers. Earlier this year, U.S. Surgeon General Vivek Murthy identified alcohol use as the nation's third leading preventable cause of cancer, following tobacco use and obesity. In the study, participants who were taking GLP-1 medications such as semaglutide, tirzepatide, or liraglutide experienced a slower rise in blood-alcohol concentration even though they consumed the same amount of alcohol as those not on the drugs. They also reported feeling less intoxicated based on their own assessments. Supported by funding from Virginia Tech's Fralin Biomedical Research Institute, the study aimed to explore both the physical and perceived effects of alcohol in people taking a GLP-1 drug. The researchers say these early findings could help shape larger, long-term studies on whether such medications might be used to reduce alcohol consumption. The study included twenty adults with a body mass index (BMI) of 30 or higher, half of whom were taking GLP-1 medication and half who were not. Participants were asked to fast before the session, then were given a snack bar to keep stomach contents consistent. Researchers measured each participant's blood pressure, pulse, breath alcohol concentration, and blood glucose levels. Ninety minutes later, they were served an alcoholic drink to finish within 10 minutes. Afterward, participants were asked several times over an hour to describe their level of intoxication, cravings, appetite, and the drink's taste, including the question, "How drunk do you feel right now?" rated from zero to ten. Those on GLP-1 medication consistently reported feeling less drunk. After the drinking portion ended, participants stayed in a recovery area while their alcohol levels dropped. Breath alcohol was measured every 30 minutes, blood glucose twice, and after three hours participants again answered follow-up questions. Four hours later, once their breath alcohol measured below 0.02 percent and they were cleared by a study physician, they were allowed to leave. "Other medications designed to help reduce alcohol intake" -- naltrexone and acamprosate -- "act on the central nervous system," said DiFeliceantonio, the study's corresponding author. "Our preliminary data suggest that GLP-1s suppress intake through a different mechanism." The drugs slow gastric emptying, which can lead to a slower rise in blood alcohol. The idea for the study initially bubbled up during a Fralin Biomedical Research Institute faculty retreat and was led by Warren Bickel, professor and director of the Addiction Recovery Research Center, who died in 2024. It built on an analysis of social media posts on the community network Reddit, in which users reported reduced cravings for alcohol when taking drugs intended to treat type 2 diabetes and obesity. "His guidance shaped every stage of this research -- from the initial idea to its final form -- and his passion for scientific discovery continues to inspire me every day," said Fatima Quddos, a graduate researcher in Bickel's lab and the first author on both studies. "Bickel's work had long focused on what happens when you delay rewards, so we asked, 'What if GLP-1s affect how the body handles alcohol?'" DiFeliceantonio said. "Ending this project was bittersweet, because it was my last collaboration with him." "He was always asking, 'How do we help people the fastest?' Using a drug that's already shown to be safe to help people reduce drinking could be a way to get people help fast," DiFeliceantonio said. While this was a pilot study, researchers said the findings showed clear differences between groups and provide early data that support larger trials testing the drugs as a therapy for people who want to reduce their alcohol use. "As a recent graduate, I'm deeply inspired by the potential this research holds -- not only for advancing our scientific understanding, but also for paving the way toward future therapies," said Quddos, who earned her doctorate from Virginia Tech's Translational Biology, Medicine, and Health Graduate Program in May. "The possibility of offering new hope to individuals struggling with addiction is what makes this work so meaningful."

来源 | 医脉通内分泌科 肥胖是一种多因素导致的慢性疾病，其特征是身体脂肪的功能失调性或过度性积累。这种疾病不仅影响个体器官的功能，还会对整个身体系统产生负面影响，从而引发一系列并发症。这些并发症可以分为两大类： 一类是由于脂肪质量增加导致的机械力改变而引发的“脂肪质量病（FAT MASS DISEASES）”，如睡眠呼吸暂停综合征（OSAS）和膝关节骨关节炎（KOA）； 另一类则是与代谢、内分泌、炎症和免疫反应失调相关的“病态脂肪疾病（SICK FAT DISEASES）”，如2型糖尿病（T2DM）、心血管疾病（CVD）和代谢功能障碍相关脂肪肝疾病（MASLD）等。 2025年10月2日，《欧洲肥胖研究协会 (EASO) 关于肥胖及其并发症药理治疗的框架》于nature medicine重磅发布，为肥胖及其并发症的临床治疗提供了全新的视角。 图 EASO针对肥胖个体的治疗建议 肥胖管理：从单一减重到全面健康改善 传统的肥胖管理主要集中在体重减轻上，但EASO的新框架强调，肥胖管理应采用更全面的方法，不仅要减轻体重，还要预防、解决或改善并发症，提升心理健康、身体素质、社交功能以及整体健康和生活质量。行为改变（包括治疗性营养、治疗性体育活动、压力管理和睡眠改善）是肥胖管理的基础，同时可能需要结合心理支持、肥胖管理药物以及代谢或减重手术（外科和内镜手术）。 近年来，可用于治疗肥胖的药物数量稳步增加，为临床医生提供了更多选择。不同的药物在减轻体重和对肥胖相关并发症的影响方面存在差异，因此，基于个体患者特征的个体化治疗变得可行且必要。EASO提出的治疗策略旨在帮助临床医生根据每位患者的健康背景选择合适的药物。 药物治疗：选择与考量 01 没有并发症的个体：减重为主要目标 在没有并发症的个体中，减轻体重仍然是治疗的主要目标，以降低发生并发症的风险。所有获得批准的药物与安慰剂相比都能显著减轻体重，但不同药物在减轻体重方面的效果存在差异。例如，替尔泊肽和司美格鲁肽在与安慰剂相比时，体重减轻超过10%，而奥利司他、naltrexone–bupropion、利拉鲁肽和phentermine–topiramate的效果则较小。 在选择药物时，应考虑药物对体重减轻的效果、对并发症的影响以及安全性。根据临床试验结果，替尔泊肽和司美格鲁肽在需要显著减轻体重时应作为首选药物。而对于需要适度减轻体重的个体，可以选择范围更广的药物。 02 已存在并发症的个体：精准治疗 对于已经存在并发症的个体，选择最合适的药物应基于药物对并发症改善或缓解的证据。药物对肥胖相关并发症的影响是异质性的，并不总是与体重减轻的程度成正比，这可能反映了药物除了减轻体重之外的直接药理作用。因此，EASO的治疗策略是基于药物对特定并发症的影响的科学证据合成而开发的。 ➤睡眠呼吸暂停综合征（OSAS）：目前，只有替尔泊肽在针对肥胖个体的OSAS影响的随机对照试验中显示出更高的OSAS缓解率，并显著降低了呼吸暂停-低通气指数。因此，替尔泊肽应被视为肥胖和OSAS患者的一线治疗药物。 ➤膝关节骨关节炎（KOA）：在针对肥胖和膝关节骨关节炎个体的两项随机对照试验中，分别研究了利拉鲁肽和司美格鲁肽。研究表明，司美格鲁肽比利拉鲁肽更能减轻疼痛。因此，司美格鲁肽应被视为肥胖和膝关节骨关节炎患者的一线治疗药物。 ➤糖尿病前期和2型糖尿病：在针对糖尿病前期和糖尿病患者的试验中，替尔泊肽、司美格鲁肽、利拉鲁肽以等都能显著改善血糖参数，并在不同程度上实现2型糖尿病的缓解。替尔泊肽、司美格鲁肽和利拉鲁肽还降低了超重/肥胖和糖尿病前期个体进展为2型糖尿病的发病率。因此，替尔泊肽和司美格鲁肽应作为肥胖和血糖异常个体的首选药物。 ➤心血管疾病：在针对心血管结局的随机对照试验中，司美格鲁肽显示出显著降低有心血管事件史个体的主要不良心血管事件（MACE）发病率的效果，而naltrexone–bupropion则未显示出显著的心血管益处。因此，司美格鲁肽应推荐给有心血管病史的个体。 ➤心力衰竭：在针对心力衰竭患者的试验中，司美格鲁肽和替尔泊肽均显示出降低心力衰竭住院风险的效果，无论患者是射血分数保留型还是射血分数降低型心力衰竭。尽管如此，目前的数据仍不足以对这两种药物分别在不同情况下的使用提出具体建议。目前，替尔泊肽和司美格鲁肽应被视为肥胖和心力衰竭患者的一线治疗药物。 ➤代谢功能障碍相关脂肪性肝病（MASLD）：在针对MASLD患者的试验中，只有替尔泊肽显示出对代谢功能障碍相关脂肪性肝炎（MASH）的缓解和肝纤维化改善的效果。目前推荐使用替尔泊肽治疗肥胖合并MASLD患者。值得注意的是，未纳入本指南的3期ESSENCE试验（因该试验于2025年1月31日后发表）显示，司美格鲁肽与替尔泊肽类似，与MASH和肝纤维化的显著改善相关。 未来展望：个体化治疗与新发现 尽管大多数药物尚未针对特定并发症进行专门评估，但随着对肥胖作为脂肪质量疾病和病态脂肪疾病的理解不断发展，药物治疗的潜力也在不断增长。未来，药物有望对更广泛的并发症产生积极影响，包括慢性肾脏病、神经退行性疾病、多囊卵巢综合征、某些癌症和心理健康状况等。 EASO提出的药物使用框架强调了根据个体情况量身定制治疗方案的重要性。这一框架基于当前的科学证据，通过系统回顾和网络荟萃分析已发表的临床试验而开发。这种方法与将肥胖视为一种基于脂肪的慢性疾病的概念一致，区分了与脂肪质量相关的主要因素和与功能失调（或“病态”）脂肪相关联的因素。 为个体量身定制治疗方案是一项复杂的任务，需要考虑多个因素，包括脂肪质量的严重程度、并发症的存在和程度、合并症和同时进行的治疗。社会经济背景、患者的价值观、期望和个人目标也必须被考虑在内。尽管没有任何治疗策略可以取代这种全面评估所需的细致临床判断，但这一工具可以为肥胖治疗的决策提供支持。鉴于药物领域的快速发展，EASO计划定期更新当前的治疗策略，以纳入最新的可用证据。 总之，EASO的最新框架为肥胖及其并发症的药理治疗提供了全面、科学的指导，强调了个体化治疗的重要性，并为临床医生在肥胖治疗中的决策提供了有力的支持。 参考文献 McGowan, B., Ciudin, A., Baker, J.L. et al. Framework for the pharmacological treatment of obesity and its complications from the European Association for the Study of Obesity (EASO). Nat Med (2025). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41591-025-03765-w 责编｜Zelda 封面图来源｜视觉中国 超57%医务人员收入下降，集体降薪时代，不同医院不同医生的收入差距 刚刚！2025年诺贝尔生理学或医学奖重磅揭晓！ 医脉通是专业的在线医生平台，“感知世界医学脉搏，助力中国临床决策”是平台的使命。医脉通旗下拥有「临床指南」「用药参考」「医学文献王」「医知源」「e研通」「e脉播」等系列产品，全面满足医学工作者临床决策、获取新知及提升科研效率等方面的需求。 ☟戳这里，更有料！