The investigators plan to conduct an R61/33 hybrid type 2 implementation-effectiveness trial that includes 1) a one-year exploratory R61 phase that will enable the development of the intervention protocol needed for the R33 trial phase including concrete R61 phase milestones; 2) a four-year R33 phase that will include a concurrent implementation evaluation and a randomized control trial.

开始日期2026-07-01

申办/合作机构

Duke University

[+3]

NCT05339256

/ Not yet recruiting临床2期IIT

A Randomized, Controlled Trial of Sublingual Buprenorphine Through Telemedicine vs In-Person Care as Usual in the Treatment of Opioid Use Disorder

This study will compare in-person induction and maintenance dosing of sublingual buprenorphine to induction and maintenance dosing of sublingual buprenorphine through comprehensive telehealth sessions and telehealth medication for opioid use disorder (MOUD).

开始日期2026-06-01

申办/合作机构

The New York State Psychiatric Institute

[+1]

NCT07176351

/ Not yet recruiting临床4期IIT

Acceptability and Feasibility of Extended-Release Subcutaneous Buprenorphine on a Mobile Pharmacy Clinic: A Pilot Study

This exploratory project will assess the acceptability and feasibility of monthly extended-release subcutaneous buprenorphine (BRIXADI; XR-B) to treat opioid use disorder (OUD) among persons in the community receiving care on a mobile pharmacy clinic (MPC).
Participants who are interested in initiating monthly or weekly injections of subcutaneous XR-B (BRIXADI) as a treatment for their OUD will be enrolled in a 6-month study assessing the acceptability and feasibility of receiving XR-B on an MPC.

开始日期2026-04-01

申办/合作机构

Yale University

[+1]

100 项与丁丙诺啡相关的临床结果

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100 项与丁丙诺啡相关的转化医学

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100 项与丁丙诺啡相关的专利（医药）

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10,946

项与丁丙诺啡相关的文献（医药）

2026-12-31·Canadian Journal of Pain-Revue Canadienne de la Douleur

Patient perspectives on buprenorphine/naloxone for chronic noncancer pain: A qualitative interview study

Article

作者: Halpape, Katelyn ; Jorgenson, Derek ; Rogers, Marla

Background:

Buprenorphine/naloxone (Suboxone) is an emerging option for chronic noncancer pain (CNCP), but evidence on transitioning patients from full opioid agonists remains limited. At the University of Saskatchewan Chronic Pain Clinic (UCPC) in Saskatchewan, Canada, pharmacists support these transitions within a unique interdisciplinary model.

Aim:

The aim of this study was to explore patient perspectives on transitioning to and using buprenorphine/naloxone for CNCP.

Methods:

This qualitative study involved one-on-one semistructured interviews with current and former UCPC patients who had transitioned to buprenorphine/naloxone for CNCP. Participants were invited by email to complete semistructured interviews via Zoom or telephone with a trained facilitator. The interview guide was informed by a literature review and pretested. Recorded interviews were transcribed using an artificial intelligence-supported platform, reviewed for accuracy, and analyzed in NVivo 14 using thematic analysis.

Results:

Seven participants (five females, two males; average age 57 years) were interviewed. Most had used opioids long term for pain prior to transition. Experiences varied: some transitioned easily, whereas others required more time or experienced discomfort. Buprenorphine/naloxone tablet size and taste were the most common negative experiences. Side effects were mild (e.g. drowsiness, constipation). Some expressed concern about long-term use and desired clearer communication during transitions. Although buprenorphine/naloxone was not uniformly experienced as effective for pain relief, most would recommend buprenorphine/naloxone to others.

Conclusion:

Patient experiences at UCPC suggest that though buprenorphine/naloxone is not a universal solution for CNCP, it may be an effective option for carefully selected individuals. Side effects were tolerable, and most would recommend the treatment. Improved communication during transitions may enhance patient experiences.

2026-12-01·Current Pain and Headache Reports

Buprenorphine Microinduction Treatment in Tri-Diagnosis Patients with Opioid Use Disorder and Chronic Non-Cancerous Pain

Review

作者: Murphy, Austin ; Reilly, Madelyn ; Lynch, Paul ; Syed, Anisa ; Abd-Elsayed, Alaa

Tri-diagnosis patients cause prevalent economic and healthcare burdens. A tri-diagnosis patient presents with three concurrent conditions: a mental illness, a substance use disorder, and an additional chronic medical condition. The medical conditions of interest include chronic non-cancerous pain (CNCP) and co-occurring with opioid use disorder (OUD). These patients are complex to treat, and an intensive outpatient program (IOP) would be appropriate to address the severity of their symptoms. OUD is prevalent among this population, especially for those in poverty, and in the United States generally. However, it is not fully addressed in the United States, and for those who receive treatment, only 25% will receive medication-assisted treatment. Buprenorphine Microdosing Induction (BPMI), often referred to as the Bernese method, is a novel approach traditionally used in opioid use disorder (OUD) treatment. It can serve as medication-assisted treatment for OUD treatment and pain management simultaneously in an IOP. Because buprenorphine is a partial-opioid agonist, it mitigates withdrawal symptoms and side effects of opioid withdrawal while still providing analgesic effects. Furthermore, this article describes the protocol of BPMI for tri-diagnosis patients who are struggling with OUD and chronic pain and explores the substantial positive outcomes and higher efficacy in contrast to opioids.

2026-12-01·Current Pain and Headache Reports

Perioperative Management of Patients on Buprenorphine

Review

作者: Mydlo, Nicholas ; Ng, Jessica ; Silverman, Matthew ; Hines, Roberta ; Hickey, Thomas ; Vadivelu, Nalini ; Chowdhari, Sean ; Kodumudi, Gopal ; Thomas, Donna-Ann ; Dextras, Christopher

PURPOSE OF THE REVIEW:

Our review discusses the pharmacologic profile of buprenorphine, then dives into the current literature regarding buprenorphine's use to treat chronic pain, opioid use disorder, and acute postoperative pain. We aim to focus on how that literature may influence the perioperative management of patients on buprenorphine and prompt reconsideration of buprenorphine as a frontline opioid analgesic.

RECENT FINDINGS:

Buprenorphine has been used effectively for both acute and chronic pain management, for the treatment of opioid withdrawal, and for the treatment of opioid use disorder due to its unique pharmacological profile. Historically, there has been controversy over the best practice recommendations for buprenorphine use in the perioperative setting, though the data now overwhelmingly refutes the full discontinuation of buprenorphine preoperatively. It has also been seen in recent times that buprenorphine is at least as effective as usual care opioids for acute pain management, with important safety advantages. Expanding our analgesic toolkit to more thoroughly understand the unique mechanism of action and properties of buprenorphine is paramount in our treatment of perioperative pain in both opioid-naïve and opioid-tolerant patients.

219

项与丁丙诺啡相关的新闻（医药）

2026-06-12

·PRNewswire

Braeburn to Present Research at CPDD 2026 Annual Meeting, Including Data on Withdrawal Suppression and Real-World Treatment Retention in Patients With Opioid Use Disorder

PLYMOUTH MEETING, Pa., June 12, 2026 /PRNewswire/ -- Braeburn today announced it will present two oral presentations and two posters at the 88th Annual Scientific Meeting of the College on Problems of Drug Dependence (CPDD), taking place June 13–17, 2026, in Portland, Oregon, expanding the clinical and real-world evidence base for BRIXADI® (buprenorphine) extended-release injection for subcutaneous use (CIII) in the fentanyl era. Oral Presentations: First Dose Withdrawal Suppression With Injectable Weekly and Monthly Buprenorphine (CAM2038) and the Relationship Between Buprenorphine Plasma Concentrations and Withdrawal Suppression in Participants With Opioid Use Disorder This presentation will share findings from a post hoc analysis evaluating the first dose effect of Weekly and Monthly BRIXADI on opioid withdrawal and self-reported illicit drug use in participants with moderate to severe OUD and the association between buprenorphine plasma concentrations and withdrawal suppression. Late-Breaking: Office-Based Treatment Retention Among Patients With OUD and Recent Fentanyl Use: Extended-Release Injectable Buprenorphine vs Sublingual Buprenorphine This presentation will share findings from a real-world retrospective analysis of electronic medical record data examining treatment retention among patients with OUD and recent fentanyl use who received BRIXADI compared to those on sublingual buprenorphine over a 6-month observation period. Posters: Real-World Utilization Trends of Weekly and Monthly Injectable Buprenorphine (CAM2038) in the United States During the Era of High Potency Synthetic Opioids A retrospective analysis of specialty pharmacy dispensing data for BRIXADI evaluated the distribution of available doses and formulations and longitudinal utilization trends since becoming available in the United States. National and Regional Trends in Fentanyl-Associated Polysubstance Use: A Cross-Sectional Analysis of Urine Drug Testing in the United States, 2016–2025 A retrospective, cross-sectional analysis of definitive urine drug testing results examined national and regional patterns of concomitant drug use over time among patients with substance use disorders in the United States who use fentanyl. About BRIXADI® BRIXADI is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine. BRIXADI should be used as part of a complete treatment plan that includes counseling and psychosocial support. IMPORTANT SAFETY INFORMATION WARNING: RISK OF SERIOUS HARM OR DEATH WITH INTRAVENOUS ADMINISTRATION; BRIXADI RISK EVALUATION AND MITIGATION STRATEGY Serious harm or death could result if administered intravenously. BRIXADI forms a liquid crystalline gel upon contact with body fluids and may cause occlusion, local tissue damage, and thrombo-embolic events, including life-threatening pulmonary emboli, if administered intravenously. Because of the risk of serious harm or death that could result from intravenous self-administration, BRIXADI is only available through a restricted program called the BRIXADI REMS. Healthcare settings and pharmacies that order and dispense BRIXADI must be certified in this program and comply with the REMS requirements. BRIXADI (buprenorphine) extended-release injection (weekly, 50 mg/mL buprenorphine) and BRIXADI (monthly, 356 mg/mL buprenorphine) are different formulations. Doses of BRIXADI (weekly) cannot be combined to yield an equivalent monthly dose. CONTRAINDICATIONS BRIXADI is contraindicated in patients with hypersensitivity (e.g., anaphylactic shock) to buprenorphine or any other ingredients in the solution for injection. WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse: BRIXADI contains buprenorphine, a Schedule III controlled substance that can be abused in a manner similar to other opioids. Buprenorphine is sought by people with opioid use disorder and is subject to criminal diversion. Monitor all patients for progression of opioid dependence and addictive behaviors. Life-Threatening Respiratory and Central Nervous System (CNS) Depression: Buprenorphine has been associated with life-threatening respiratory depression and death. Use BRIXADI with caution in patients with compromised respiratory function. Due to its extended-release characteristics, if BRIXADI is discontinued as a result of compromised respiratory function, monitor patients for ongoing buprenorphine effects for approximately 1 month for BRIXADI (weekly) and for approximately 4 months for BRIXADI (monthly). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose. Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose: Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene) and discuss the importance of having access to an opioid overdose reversal agent. Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose, strongly consider prescribing or recommending an opioid overdose reversal agent for the emergency treatment of an opioid overdose, both when initiating and renewing treatment with BRIXADI. If an opioid overdose reversal agent is prescribed, educate patients and caregivers on how to treat with such an agent, and emphasize the importance of calling 911 or getting emergency medical help, even if an agent is administered. Concomitant Use of Benzodiazepines or other CNS Depressants: Concomitant use of buprenorphine and benzodiazepines or other CNS depressants (e.g., alcohol, non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids) increases the risk of adverse reactions including overdose, respiratory depression, and death. Ensure that other healthcare providers prescribing benzodiazepines or other CNS depressants are aware of the patient's buprenorphine treatment and coordinate care to minimize the risk associated with concomitant use. Inform patients and caregivers that potentially fatal additive effects may occur if BRIXADI is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider. Neonatal Opioid Withdrawal Syndrome, Pregnancy, and Lactation: Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy. NOWS may be life-threatening if not recognized and treated in the neonate. Healthcare providers should observe newborns for signs of NOWS and manage accordingly. Advise pregnant women receiving opioid addiction treatment with BRIXADI of the risk of neonatal opioid withdrawal syndrome. Warn patients that buprenorphine passes into breast milk. Advise the nursing mother taking buprenorphine to monitor the infant for increased drowsiness and breathing difficulties. Adrenal Insufficiency: If adrenal insufficiency is diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. Risk of Opioid Withdrawal with Abrupt Discontinuation: Patients who elect to discontinue BRIXADI treatment should be monitored for withdrawal signs and symptoms with consideration given to the product's extended-release characteristics. Risk of Hepatitis, Hepatic Events, and Use in Patients with Impaired Hepatic Function: Liver function tests should be performed on all patients prior to initiation, during treatment, and if a hepatic event is suspected. Because buprenorphine levels cannot be rapidly decreased, patients with pre‐existing moderate to severe hepatic impairment are not candidates for treatment with BRIXADI. Patients who develop moderate to severe hepatic impairment while being treated with BRIXADI should be monitored for signs and symptoms of toxicity or overdose of buprenorphine and may require a dose adjustment. Hypersensitivity Reactions: Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported in patients receiving buprenorphine-containing products. The most common signs and symptoms include rashes, hives, and pruritus. The BRIXADI needle cap is synthetically derived from natural rubber latex which may cause allergic reactions in latex-sensitive individuals. Precipitation of Opioid Withdrawal in Patients Dependent on Full Opioid Agonists: BRIXADI injection may precipitate opioid withdrawal signs and symptoms in individuals physically dependent on full opioid agonists such as heroin, morphine, or methadone before the effects of the full opioid agonist have subsided. In patients who are new entrants to treatment, to avoid precipitating an opioid withdrawal syndrome, administer a 4 mg test dose of transmucosal buprenorphine when objective signs of mild to moderate withdrawal appear and monitor for precipitated withdrawal before injecting BRIXADI. Risks Associated with Treatment of Emergent Acute Pain: While on BRIXADI, situations may arise where patients need acute pain management, or may require anesthesia. Treat patients receiving BRIXADI with non-opioid analgesic whenever possible. Patients requiring opioid therapy for analgesia may be treated with a high-affinity full opioid analgesic under the supervision of a healthcare provider, with particular attention to respiratory function. Higher doses may be required for analgesic effect. Therefore, a higher potential for toxicity exists with opioid administration. Advise patients of the importance of instructing their family members, in the event of emergency, to inform the treating healthcare provider or emergency room staff that the patient is being treated with BRIXADI. Use in Opioid Naïve Patients: There have been reported deaths of opioid naïve individuals who received a 2 mg dose of buprenorphine as a sublingual tablet. BRIXADI is not appropriate for use in opioid naïve patients. Patients at Risk for Arrhythmia: Thorough QT studies with buprenorphine products have demonstrated QT prolongation ≤ 15 msec. This QTc prolongation effect does not appear to be mediated by hERG channels. Based on these two findings, buprenorphine is unlikely to be pro-arrhythmic when used alone in patients without risk factors. The risk of combining buprenorphine with other QT-prolonging agents is not known. Impairment of Ability to Drive and Operate Machinery: BRIXADI may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery. Caution patients about driving or operating hazardous machinery until they are reasonably certain that BRIXADI does not adversely affect their ability to engage in such activities. Orthostatic Hypotension: Buprenorphine may produce orthostatic hypotension in ambulatory patients. Elevation of Cerebrospinal Fluid Pressure: Buprenorphine may elevate cerebrospinal fluid pressure and should be used with caution in patients with head injury, intracranial lesions, and other circumstances when cerebrospinal pressure may be increased. Elevation of Intracholedochal Pressure: Buprenorphine has been shown to increase intracholedochal pressure, as do other opioids, and thus should be administered with caution to patients with dysfunction of the biliary tract. Effects in Acute Abdominal Conditions: Buprenorphine may obscure the diagnosis or clinical course of patients with acute abdominal conditions. Unintentional Pediatric Exposure: Buprenorphine can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed to it. ADVERSE REACTIONS Adverse reactions commonly associated with BRIXADI administration (in ≥5% of patients) were injection site pain, headache, constipation, nausea, injection site erythema, injection site pruritus, insomnia, and urinary tract infection. DRUG INTERACTIONS CYP3A4 Inhibitors and Inducers: Monitor patients starting or ending CYP3A4 inhibitors or inducers for potential over or under dosing. Serotonergic Drugs: If concomitant use is warranted, monitor for serotonin syndrome, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. USE IN SPECIFIC POPULATIONS Lactation: Buprenorphine passes into the mother's milk. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for buprenorphine treatment and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. Geriatric Patients: Monitor geriatric patients receiving BRIXADI for sedation or respiratory depression. Moderate to Severe Hepatic Impairment: BRIXADI is not recommended for use in patients with pre-existing moderate to severe hepatic impairment. To report SUSPECTED ADVERSE REACTIONS, contact Braeburn at 1-833-274-9234 or FDA at 1-800-FDA-1088 or . Please see the BRIXADI Medication Guide and Full Prescribing Information , including BOXED WARNING, at BRIXADI.com or accompanying this document. About Braeburn Braeburn is dedicated to delivering solutions for people living with the serious consequences of opioid use disorder. At Braeburn, we challenge the status quo and champion transformation of the management of opioid use disorder (OUD) by partnering with the community to create a world where every person with OUD gets the best possible care and opportunity to reach their full potential. Visit braeburnrx.com to learn more. Connect with Braeburn on LinkedIn at linkedin.com/company/braeburn. For additional information, please contact: Sabrina Romano, Senior Manager of Corporate Communications & Advocacy, at [email protected] BRX-1802 June 2026 SOURCE Braeburn 21% more press release views with Request a Demo

临床3期临床结果上市批准

2026-06-05

·闻星宏宇

肠促胰素治疗的下一个十年：GLP-1RA的适应证拓展与新一代多靶点药物研发格局

基于 Nature Reviews Drug Discovery 2025 权威综述【开篇】一个价值千亿美元的医学传奇如果说过去十年全球制药行业有一个真正的"超级明星"，那非GLP-1受体激动剂莫属。从2005年首个药物获批用于2型糖尿病治疗时的"小众选择"，到如今席卷全球的减重革命，GLP-1类药物用不到20年时间完成了从边缘到中心的惊人跃迁。 2024年，semaglutide（司美格鲁肽，商品名Wegovy/Ozempic）和tirzepatide（替尔泊肽，商品名Zepbound/Mounjaro）的全球销售额合计超过400亿美元。华尔街分析师预测，到2030年GLP-1类药物市场规模将突破1000亿美元，成为人类历史上最畅销的药物类别之一。这不仅是一场医学革命，更是一场深刻影响全球公共卫生、经济格局乃至社会文化的产业变革。然而，GLP-1的故事远不止"减肥神药"这么简单。2025年初，多伦多大学Daniel J. Drucker教授——这位GLP-1领域的奠基人之一，正是他在1980年代参与了GLP-1的早期克隆和功能研究——在Nature Reviews Drug Discovery发表了这篇备受瞩目的权威综述，系统梳理了GLP-1类药物从已上市品种到研发管线、从作用机制到适应症拓展的全景图。本文基于这篇综述，结合最新临床试验数据，为您深度解读这个正在改写现代医学史的药物赛道。一、四十年磨一剑：GLP-1的传奇发展史1.1 从鳗鱼基因到肠道"智能激素" GLP-1（Glucagon-Like Peptide-1，胰高血糖素样肽-1）的故事始于1981-1982年。当时，科学家们从安康鱼（anglerfish）--早于Hila Monster.- 的胰腺中首次克隆出了proglucagon cDNA，意外发现了一个与胰高血糖素相似的肽序列。 1987年，三个独立的研究团队同时证明：这个被命名为GLP-1的肽段能以葡萄糖依赖性方式刺激胰岛β细胞分泌胰岛素——这意味着它只在血糖升高时促进胰岛素释放，血糖正常时则不会引起低血糖，这一特性使其立即成为糖尿病治疗的理想候选靶点。此后数十年，研究人员逐步揭开了GLP-1的多重生理功能：胰腺：以葡萄糖依赖性方式促进胰岛素分泌、抑制胰高血糖素释放胃肠道：延缓胃排空，降低餐后血糖峰值中枢神经系统：通过作用于下丘脑和脑干的GLP-1R阳性神经元，抑制食欲、增加饱腹感心血管系统：改善内皮功能、减少炎症、降低血压肾脏：减少白蛋白尿、保护肾功能肝脏：减少脂肪变性、改善炎症正是这些多器官、多靶点的广泛作用，为GLP-1药物日后在糖尿病和肥胖之外的适应症拓展埋下了伏笔。 GLP-1RA 的多靶点机制图选自：Drucker DJ. GLP-1-based therapies for diabetes, obesity and beyond. Nat Rev Drug Discov. 2025;24(8):631-650. doi:10.1038/s41573-025-01183-81.2 从实验室到临床的坎坷之路将GLP-1从科学发现转化为临床药物面临三大挑战：第一，代谢过快。天然GLP-1在体内的半衰期仅有1.5-2分钟，被二肽基肽酶-4（DPP-4）迅速降解，并经肾脏快速清除。第二，胃肠道耐受性差。治疗剂量的GLP-1RA如果给药过快，会导致严重的恶心、呕吐等不良反应。第三，给药途径不便。肽类药物难以穿越肠道屏障，早期只能注射给药。 1992年，一个意外的发现为突破第一个瓶颈提供了钥匙：科学家从吉拉毒蜥（Heloderma suspectum）的毒液中分离出了一种名为exendin-4的肽类，它与人类GLP-1有53%的序列同源性，但能抵抗DPP-4降解，半衰期大大延长。2005年，合成exendin-4作为exenatide（百泌达）获批上市，成为首个GLP-1RA，需要每日两次皮下注射。此后的发展堪称飞速： 2010年：首个每日一次的人源GLP-1类似物liraglutide（利拉鲁肽）获批，通过连接16碳脂肪酸侧链实现与白蛋白的非共价结合，半衰期延长至13-15小时 2012年：首个每周一次的exenatide缓释微球制剂上市 2014年：每周一次的dulaglutide（度拉糖肽）和liraglutide 3mg用于肥胖适应症先后获批 2017-2021年：semaglutide以每周一次注射和每日一次口服两种剂型先后获批，2.4mg高剂量版（Wegovy）开启了医学减重新时代 2022-2023年：首个GIPR-GLP-1R双靶点激动剂tirzepatide先后获批用于2型糖尿病和肥胖，疗效全面超越semaglutide1.3 关键里程碑时间线年份里程碑事件 1981-82 安康鱼proglucagon cDNA克隆，GLP-1序列被发现 1987 GLP-1被证实可刺激胰岛素分泌 1992 从毒蜥毒液中分离出exendin-4 2005 首个GLP-1RA exenatide获批（每日两次） 2006 首个DPP-4抑制剂sitagliptin获批 2010 首个每日一次GLP-1RA liraglutide获批 2012 首个每周一次GLP-1RA（exenatide ER）获批 2014 首个GLP-1药物肥胖适应症获批（liraglutide 3mg） 2016 首个GLP-1RA心血管结局试验（LEADER）阳性结果公布 2017Semaglutide 注射剂获批（SUSTAIN项目） 2019口服semaglutide 获批（PIONEER项目） 2021 Semaglutide 2.4mg（Wegovy）获批用于肥胖 2022Tirzepatide 获批（SURPASS/SURMOUNT项目） 2023 Tirzepatide肥胖适应症获批（Zepbound） 2024 SELECT试验显示心血管获益；FLOW试验肾脏保护数据 2025 Tirzepatide睡眠呼吸暂停适应症获批；orforglipron III期进行中选自：Drucker DJ. GLP-1-based therapies for diabetes, obesity and beyond. Nat Rev Drug Discov. 2025;24(8):631-650. doi:10.1038/s41573-025-01183-8二、已上市药物格局：从"够用"到"更强"2.1 上市药物全景对比截至目前，全球已批准多款GLP-1类药物，覆盖了从每日两次注射到每周一次、从纯GLP-1R激动到多受体协同的多种类型：药物通用名靶点给药频率半衰期减重效果代表试验获批年份Exenatide 艾塞那肽 GLP-1R 每日两次 ~2.4h 1-2% AMIGO 2005Lixisenatide 利西那肽 GLP-1R 每日一次 ~3h 2-3% ELIXA 2016Liraglutide 利拉鲁肽 GLP-1R 每日一次 13-15h 3-4% LEADER/SCALE 2010/2014Exenatide QW 艾塞那肽周制剂 GLP-1R 每周一次 - 2-4% DURATION 2012Dulaglutide 度拉糖肽 GLP-1R 每周一次 - 2-4% REWIND 2014Semaglutide 司美格鲁肽 GLP-1R 每周注射/每日口服 ~7天 10-17% SUSTAIN/STEP 2017/2021Tirzepatide 替尔泊肽 GIPR+GLP-1R 每周一次 ~5天 15-22% SURPASS/SURMOUNT 2022/20232.2 Semaglutide：当前市场的"王者" Semaglutide通过在第26位赖氨酸上连接C18十八烷二酸脂肪酸侧链，实现了非共价白蛋白结合，半衰期延长至约7天，适合每周一次给药。它同时抵抗DPP-4降解，且达到峰浓度的时间较慢，有助于改善耐受性。降糖方面：SUSTAIN项目显示，semaglutide 1mg每周一次在HbA1c降低方面优于dulaglutide 1.5mg、liraglutide 1.8mg和胰岛素。与胰岛素 glargine的头对头比较（SUSTAIN-4）显示，semaglutide在HbA1c降低和体重减轻方面均更优，且低血糖发生率更低。2mg高剂量进一步增强了降糖和减重效果。减重方面：STEP项目涵盖多种人群，semaglutide 2.4mg每周一次在68周内实现了10-17%的体重下降，最高可达40%的受试者实现≥20%减重。STEP UP试验中，更高剂量7.2mg在72周内实现了20.7%的体重下降（安慰剂校正18.3%），33%的受试者减重超过25%。口服制剂：与SNAC（N-(8-[2-羟基苯甲酰基]氨基)辛酸钠）共配方的口服semaglutide生物利用度虽仅约1%，但在PIONEER项目中证明了有效的降糖作用。25mg和50mg更高剂型的口服semaglutide正在开发中，OASIS 1试验中50mg口服在68周内实现了12.7%的安慰剂校正减重。2.3 Tirzepatide："双管齐下"的新标杆 Tirzepatide是首个获批的GIPR-GLP-1R双靶点激动剂，是一种39个氨基酸的酰化肽，C20脂肪酸二酸通过连接子连接到第20位赖氨酸。其半衰期约5天，达峰时间24-48小时。 tirzepatide的独特之处在于：优先激活GIPR（对GLP-1R的效力约弱5倍）在GLP-1R上表现出偏向性信号（biased signalling），偏向cAMP生成而非β-arrestin招募，这可能有助于改善疗效和耐受性的平衡 SURPASS项目（2型糖尿病）：与semaglutide 1mg的头对头比较（SURPASS-2）中，tirzepatide 5mg、10mg、15mg三个剂量在HbA1c降低和体重减轻方面全部优于semaglutide 15mg剂量组HbA1c降低达2.58%，体重下降11.2kg（semaglutide组为5.7kg）不良反应发生率与semaglutide相当 SURMOUNT项目（肥胖）： SURMOUNT-1：tirzepatide 15mg在72周内实现22.5%的体重下降（安慰剂校正20%），非糖尿病患者减重效果更好 SURMOUNT-2：合并T2D的肥胖患者中，最高剂量实现15.7%的安慰剂校正减重 SURMOUNT-3：强化生活方式干预后使用tirzepatide，总减重达26.6% SURMOUNT-5：与semaglutide 2.4mg的头对头比较中，tirzepatide 20.2% vs 13.7%（ tirzepatide 31.6%实现≥25%减重 vs semaglutide 16.1%）停药后的体重维持（SURMOUNT-4）：使用tirzepatide 36周后停药，1年后仍有46.5%的受试者维持≥10%减重，25.9%维持≥15%减重这一数据明显优于semaglutide STEP 1扩展试验的结果（停药后大幅反弹），提示tirzepatide可能有更持久的体重维持效应 2.4 安全性特征：需要了解什么？所有GLP-1类药物的主要不良反应是胃肠道反应（恶心、腹泻、便秘、呕吐），这反映了GLP-1R在中枢神经系统中介导的厌恶性反应以及延缓胃排空的外周作用。重要的是：胃肠道不良事件与减重幅度之间相关性较弱更平缓的剂量滴定方案可改善耐受性严重脱水导致的急性肾损伤是需要警惕的罕见并发症胆囊疾病（胆囊炎、胆石症）发生率一般<1%，与剂量和疗程相关。胰腺炎和胰腺癌风险：早期担忧未得到临床数据支持。甲状腺C细胞肿瘤：禁用于有甲状腺髓样癌病史或MEN2综合征患者。已开展超过20年的登记研究持续监测中。三、新型GLP-1RA：谁能挑战现有王者？3.1 小分子口服GLP-1RA：颠覆性的"游戏规则改变者" 小分子口服药物如果能达到与肽类注射剂相当的疗效，将从根本上改变GLP-1药物的市场格局——无需注射、无需冷链、生产成本更低、供应更容易扩大。Orforglipron（LY3502970，礼来） Orforglipron是临床进展最快的小分子GLP-1RA，最初由中外制药（Chugai）发现。它是一个部分激动剂，偏向G蛋白激活，β-arrestin招募几乎可忽略。独特优势：不受食物影响（AUC和Cmax在进食状态下仅降低18-24%，Tmax和半衰期无差异），因此无需空腹服用一日一次口服即可临床试验数据： 2型糖尿病：26周试验中，最高剂量实现1.67%的HbA1c降低和7.9kg体重下降，优于dulaglutide 1.5mg 肥胖：36周试验中，12-45mg剂量实现7.1%-12.5%的安慰剂校正减重，停药率10-17% ACHIEVE I III期试验（40周）：A1c降低1.3%-1.6%，最高剂量7.9%减重正在进行的大型III期项目： ATTAIN（肥胖） ATTAIN-MAINTAIN（tirzepatide减重后orforglipron维持） ACHIEVE-4（vs 胰岛素glargine，心血管高风险T2D）睡眠呼吸暂停和高血压的新适应症探索Danuglipron（辉瑞） Danuglipron是一种偏向cAMP的小分子GLP-1RA，但其开发之路颇为坎坷： Tmax仅2-6小时，半衰期4.3-6.1小时，需要每日两次给药 200mg BID的最高剂量组中46%因不良事件停药 2025年4月，辉瑞宣布终止danuglipron开发，原因是一例药物性肝损伤事件AZD5004（ECC5004，阿斯利康/诚益生物） AZD5004是一种偏向性小分子GLP-1RA，偏向cAMP积累，几乎不引起β-arrestin 2招募或受体内化： Tmax 8-12小时，半衰期10.7-25小时，每日一次食物不影响暴露量 28天试验中，50mg组减重5.8% 正在进行的VISTA试验（IIB期，肥胖26周）和SOLSTICE试验（IIB期，T2D 26周）CT-996（罗氏/Carmot Therapeutics） CT-996是另一种偏向性小分子GLP-1RA，EC50仅0.49 nM： Tmax 8-9.6小时，半衰期17-22小时 28天试验中，120mg每日一次实现6.1%的安慰体校正减重不受食物影响 II期试验计划2025年启动GSBR-1290（Aleniglipron，Structure Therapeutics） GSBR-1290是每日一次口服小分子GLP-1RA，具有偏向性cAMP激活： Tmax 3-6小时，24小时药代动力学覆盖 12周试验中，120mg组实现6.2%安慰体校正减重不良事件率较高（恶心89.2%，呕吐62.2%），40.5%减量，18.9%停药后续采用更平缓的滴定方案后耐受性改善其他小分子候选药物 RGT-075（Regor）：12周试验中实现5%安慰体校正减重，IIb期进行中（最高225mg，36周） TERN-601（Terns Pharma）：28天试验中740mg组减重4.9%，半衰期仅4-6小时但可能通过肠-脑轴发挥作用 KAI-7535（Kailera）：28天试验中减重4.38kg3.2 新型肽类GLP-1RA：追求更长效、更强效MET-097（Metsera） MET-097是一种完全偏向性、长效脂质化GLP-1RA，半衰期长达380小时（约16天），有望实现每月一次给药： I期试验中，1.2mg每周一次（共5剂，无需滴定）在第36天实现7.5%减重，末剂后4周仍维持8.1%减重 12周IIa期试验中实现最高11.3%安慰体校正减重胃肠道不良反应轻至中度，呈一过性Ecnoglutide（原：先为生物） Ecnoglutide是高亲和力、cAMP偏向、DPP-4抵抗的酰化GLP-1RA，半衰期124-138小时：中国II期试验：1.2mg每周一次在20周内使T2D患者HbA1c降低2.39%（基线8.67%），减重2.76% 口服版本XW004也在开发中两项III期试验进行中GZR18（Bofanglutide，甘李药业） GZR18是一种长效脂质化GLP-1RA，在中国开发： IIb期30周试验中，每周和双周给药均有效最高48mg双周一次实现17.78%安慰体校正减重 48mg双周一次和24mg每周一次的数据接近中国III期肥胖试验进行中NPM-115（Vivani Medical） NPM-115是一种创新的皮下植入式exenatide缓释制剂，通过NanoPortal植入物给药：植入后可提供持续17周的exenatide释放首项人体试验正在进行中四、GLP-1多靶点激动剂：协同作战的新时代选自：Drucker DJ. GLP-1-based therapies for diabetes, obesity and beyond. Nat Rev Drug Discov. 2025;24(8):631-650. doi:10.1038/s41573-025-01183-8 如果说第一代GLP-1药物是"单兵作战"，那么下一代药物正在走向"多兵种协同作战"。通过同时激活多个代谢相关受体，多靶点药物有望实现1+1>2的疗效提升。 4.1 GIPR-GLP-1R双激动剂：tirzepatide的追随者们 tirzepatide的巨大成功催生了大量GIPR-GLP-1R双激动剂管线：VK2735（Viking Therapeutics） VK2735是一种肽类GIPR-GLP-1R双激动剂： VENTURE试验（II期，176人，13周）：2.5-15mg每周一次，最高实现14.7%的减重（安慰体校正13.1%），88%的受试者实现≥10%减重，且未观察到平台期口服版本：28天MAD试验中100mg组减重6.8%，II期VENTURE-Oral试验已完成入组 III期试验计划2025年启动KAI-9531（HRS9531，Kailera/恒瑞） KAI-9531是恒瑞发现、Kailera开发的GIPR-GLP-1R双激动剂，半衰期7-8天： T2D试验（20周）：4.5mg每周一次，HbA1c降低2.2%（基线8.2%），90%受试者HbA1c<6.5%，减重6.3% 肥胖试验（24周，240人）：最高6mg每周一次实现16.7%安慰体校正减重；更新的8mg剂量在36周实现21.1%安慰体校正减重，59%受试者减重>20% 不良反应轻至中度，以胃肠道为主CT-388（罗氏） CT-388是偏向性GIPR-GLP-1R激动剂： Ib期试验中，22mg每周一次在24周内实现19%减重 T1D合并肥胖/超重适应症也在探索中BGM0504（博瑞生物） BGM0504是一种C18脂肪酸二酸脂质化的GIPR-GLP-1R双激动剂，在体外和临床前研究中对两个受体的效力均高于tirzepatide： I期试验中半衰期约4天，15mg组在第15天减重5.4kg4.2 GIPR拮抗剂-GLP-1RA：一个反直觉的策略有趣的是，GIPR的功能丧失突变与人类更有利的心脏代谢表型相关——携带这些突变的人BMI更低、肥胖相关特征更少。这催生了一个看似反直觉的策略：阻断GIPR同时激活GLP-1R。Maritide（AMG-133，安进） Maritide是目前这一策略最先进的候选药物，是一种双特异性抗体：人源GIPR阻断抗体连接两个GLP-1RA肽段，分子量高达153,514 Da。 I期数据（140人）：三剂每月一次注射后，420mg组实现14.6%减重，末剂后5个月仍有受试者维持>10%减重 II期数据（592人）：肥胖人群（BMI 38）：420mg每月一次实现20%减重，98%受试者减重≥5%，LDL胆固醇降低 5%，血压降低11mmHg，CRP降低3% T2D人群（BMI 36，HbA1c 7.9%）：420mg每月一次减重17%，HbA1c降低2.2%，高敏CRP惊人地降低72% 未见对骨密度的不良影响 MARITIME III期项目已启动4.3 胰淀素（Amylin）通路：GLP-1的"最佳拍档"？胰淀素（Amylin）是另一种与胰岛素共同分泌的胰岛激素，通过中枢机制抑制食欲、延缓胃排空。将胰淀素类似物与GLP-1RA联用已成为热门策略。 Cagri-Sema（Cagrilintide + Semaglutide） Cagrilintide是一种每周一次的脂质化胰淀素类似物，单独使用时在706名超重/肥胖患者中实现7.8%安慰体校正减重，胃肠道不良反应低于liraglutide。与semaglutide 2.4mg联合的Cagri-Sema： T2D II期试验：32周减重15.6%，优于semaglutide单用（5.1%）或cagrilintide单用（8.1%） REDEFINE-1（III期，3417人）：68周近22%减重，40.4%受试者减重≥25% REDEFINE-2（T2D人群）：68周12.6%安慰体校正减重包含7000人参与的CVOT正在进行中Petrelintide（Zealand Pharma） Petrelintide是一种36个氨基酸的人胰淀素类似物，每周一次： Ib期试验（16周）：3mg组减重8.6%，恶心率16.7-33.3%，仅1人停药 42周II期试验进行中Amycretin（诺和诺德） Amycretin是一种单分子胰淀素-GLP-1肽，可同时口服和注射：口服：12周12%安慰体校正减重注射（20mg每周一次，36周）：最高22%减重（基线92.7kg）！安全性与GLP-1类一致Pemvidutide（Altimmune） Pemvidutide是一种GCGR-GLP-1R双激动剂，也是一种平衡的长效激动剂： MOMENTUM试验（48周）：2.4mg每周一次实现13.4%安慰体校正减重，78.1%的减重来源于脂肪组织超过30%的受试者在最高剂量实现≥20%减重对血糖影响较小（平衡的 glucagon-GLP-1 共激动）正在进行MASH和肥胖相关试验4.4 胰高血糖素（Glucagon）通路：代谢"加速器" 将glucagon受体（GCGR）激动与GLP-1R激动结合是一个聪明的策略：glucagon增加能量消耗、直接减少肝脏脂肪，而适当的GLP-1:glucagon比例可以保留GLP-1的降糖作用。Survodutide（BI 456906，勃林格殷格翰） Survodutide是一种29个氨基酸的酰化GCGR-GLP-1R双激动剂，对两个受体的效力均比天然肽低约10倍：通过减少食物摄入和增加能量消耗实现减重（两个作用都需要GCGR和GLP-1R） II期试验（46周）：4.8mg每周一次实现12.1%安慰体校正减重 III期试验进行中（3.6mg和6mg，T2D和非T2D肥胖） CVOT（SYNCHRONIZE-CVOT）进行中Retatrutide（LY3437943，礼来）：三靶点的"超级明星" Retatrutide是目前最受关注的GCGR-GIPR-GLP-1R三靶点激动剂，对GIPR的效力是GLP-1R的8.9倍，对GCGR和GLP-1R的效力则低一些：肥胖II期（48周）：12mg每周一次实现24.2%的体重下降，60%受试者减重>15%，最高剂量组40%实现>20%减重 T2D II期（36周）：12mg组HbA1c降低2.02%，减重16.2% MASH亚组：肝脂肪降低81.4-82.4% III期项目： TRANSCEND-T2D（T2D） TRIUMPH（肥胖） TRIUMPH OUTCOMES（CVOT+肾脏结局，10000人）Mazdutide（IBI362，信达生物/礼来） Mazdutide是一种酰化GCGR-GLP-1R双激动剂，主要在中国开发：中国T2D II期：6mg每周一次减重5.4% 中国肥胖II期：6mg每周一次24周减重12.3%；III期48周减重14.7% MRI显示肝脂肪降低约75% 已提交中国NMPA审评；礼来在美国开展酒精依赖试验其他GCGR-GLP-1R双激动剂 Efinopegdutide：肝脂肪降低72.7%（vs semaglutide 42.3%），MASH II期完成 Bioglutide（NA-931）：全球首个四靶点激动剂（glucagon+GIP+GLP-1+IGF-I），28天减重5.1%，12周最高10.4%，每日一次口服胶囊4.5 GLP-1受体靶向治疗新策略一种创新策略是将功能性分子与GLP-1配体偶联，实现对GLP-1R阳性细胞的靶向递送： GLP-1-雌激素偶联物：将雌激素靶向递送至GLP-1R阳性细胞，在小鼠中产生比单独使用更强的减重效果，且没有传统雌激素的副作用（如子宫内膜增生） GLP-1-地塞米松偶联物：将糖皮质激素靶向递送至GLP-1R阳性细胞，减重同时改善炎症，不影响下丘脑-垂体轴 GLP-1-NMDA受体拮抗剂：靶向GLP-1R阳性神经元中的谷氨酸离子通道，在肥胖小鼠中产生优于联合给药的减重效果，并诱导神经可塑性这些策略目前仍处于临床前阶段，但展示了GLP-1靶向治疗的广阔想象空间。五、适应症大爆炸：GLP-1正在征服的疾病版图 GLP-1类药物最令人兴奋的发展趋势，是其适应症正在从糖尿病和肥胖向更广泛的疾病领域快速拓展。这些拓展不仅基于减重带来的间接获益，更反映了GLP-1R在多个器官系统中的直接保护作用。 5.1 心血管疾病 ⭐ 已确立 LEADER试验（2016年）首次确立了liraglutide在T2D患者中的心血管保护作用。 SELECT试验是里程碑——17,604名有心血管疾病史但无糖尿病的超重/肥胖患者： Semaglutide 2.4mg治疗34.2个月 MACE风险降低20%（非致死性心梗、非致死性卒中、心血管死亡）全因死亡率降低19% 平均减重10.2%，但心血管获益部分独立于减重男性和女性获益程度相似 STEP-HFpEF试验： Semaglutide改善了射血分数保留性心力衰竭（HFpEF）合并肥胖患者的症状、6分钟步行距离减少了急诊就诊和住院率合并T2D和不合并T2D的人群均获益汇总分析（SELECT+FLOW+STEP-HFpEF+STEP-HFpEF DM）：心力衰竭事件风险降低31%（HR 0.69）正在进行： SURPASS-CVOT（tirzepatide vs dulaglutide，13,299人） SURMOUNT-MMO（tirzepatide在肥胖合并CVD人群） STRIDE（semaglutide在外周动脉疾病，改善步行距离13%）5.2 慢性肾病 ⭐ FDA已批准 FLOW试验（3,533人，T2D合并CKD）：因疗效显著而提前终止主要复合终点（透析、肾移植、eGFR<15、≥50%eGFR下降、肾/心血管死亡）风险降低24% 肾脏终点和心血管死亡均显著减少严重不良事件更少获益独立于SGLT-2抑制剂使用 SELECT试验肾脏亚组（非糖尿病人群）：复合肾脏终点风险降低22% FDA已批准semaglutide用于延缓T2D患者CKD进展的新适应症。5.3 代谢性肝病（MASH/MASLD） ESSENCE试验（semaglutide，800人，MASH+F2-F3纤维化）： 72周时62.9%实现脂肪性肝炎缓解且纤维化未恶化（安慰剂34.1%）纤维化改善≥1期：37% vs 22.5% Tirzepatide MASH试验（52周）： 15mg组62%实现MASH缓解（安慰剂仅约20%） 51%实现纤维化改善≥1期减重-15.6% Survodutide MASH试验（48周，293人）： 4.8mg组62%实现MASH缓解（安慰剂14%）纤维化改善≥1期：36% vs 22% Retatrutide MASLD亚组：肝脂肪降低81-82%5.4 睡眠呼吸暂停 ⭐ FDA已批准 Tirzepatide在469名肥胖合并中重度OSA患者中实现了：呼吸暂停低通气指数（AHI）显著降低睡眠障碍和低氧负荷减少体重、血压和CRP均下降 FDA已批准tirzepatide作为首个治疗肥胖相关中重度OSA的药物，标志着GLP-1正式进入呼吸疾病领域。5.5 骨关节炎 STEP-9试验（407人，68周）： Semaglutide使肥胖合并膝骨关节炎患者减重13.7% 显著改善疼痛评分和身体功能减少镇痛药使用两组严重不良事件相似5.6 神经退行性疾病 🔄 多项III期进行中帕金森病：早期小型试验（exenatide）曾报告阳性结果但最大规模的96周试验（194人，exenatide每周一次）未能显示对主要终点（运动和非运动评分）的获益 NLY01（pegylated exenatide）36周试验也未能显示获益结果令人失望，但不排除特定亚群获益的可能性阿尔茨海默病： EVOKE/EVOKE+试验正在进行中（口服semaglutide，55-85岁，轻度认知障碍或轻度痴呆）基于脑脊液生物标志物或PET确认淀粉样蛋白病理预计2025-2026年公布结果 5.7 物质使用障碍 🔄 早期探索中机制基础：GLP-1R在奖赏系统和享乐行为相关的脑区表达，可能调控成瘾行为。临床数据： Semaglutide 9周试验（48名中度酒精使用障碍）：减少实验室环境中酒精摄入量、每日饮酒量和饮酒渴望瑞典真实世界数据（227,866人）：GLP-1RA使用与酒精使用障碍住院风险降低相关美国VA系统数据（215,970人）：GLP-1RA使用与物质使用障碍风险降低、神经退行性疾病（包括阿尔茨海默病）发生率下降相关正在进行： Tirzepatide+丁丙诺啡治疗阿片使用障碍（II期）多项semaglutide治疗酒精使用障碍、阿片使用障碍和吸烟的II期试验六、口服小分子GLP-1：下一个千亿战场小分子口服GLP-1RA因其生产成本更低、无需冷链储存运输、患者依从性更好、供应更容易大规模扩大等优势，被视为可能真正" democratize" GLP-1治疗的关键。 Orforglipron目前处于领跑位置，其无需空腹服用的便利性是一个重要差异化优势。AZD5004、GSBR-1290、CT-996等紧随其后，竞争格局日趋激烈。关键问题是：小分子能否达到与肽类注射剂相当的疗效？从现有数据看，小分子单药减重效果（7-13%）普遍低于semaglutide注射剂（15%）和tirzepatide（20%），但考虑到口服的便利性和潜在的成本优势，如果能在疗效、价格和可及性之间找到最佳平衡，仍有望占据巨大市场份额。诺和诺德也在探索口服GLP-1RA VK2735（28天6.8%减重）和口服tirzepatide类似物的可能性。七、理性看待：挑战、争议与未解之谜7.1 体重反弹：长期治疗的必要性 STEP 1扩展试验： 68周semaglutide平均减重17.3% 停药后52周反弹11.6%，净保留仅5.6% SURMOUNT-4试验： 36周tirzepatide后停药 1年后46.5%维持≥10%减重，明显优于semaglutide 启示：tirzepatide可能有更持久的"代谢记忆"效应，但长期治疗对大多数患者仍是必要的。间歇治疗、药物假期、减至维持剂量的最佳策略仍有待探索。7.2 肌肉流失："健康减重"的新命题减重20-25%可能伴随显著的肌肉量减少（sarcopenia），这与不良预后和死亡率增加相关。关键问题包括： GLP-1药物减重的脂肪/瘦体重比例尚不完全清楚规律抗阻运动可在liraglutide治疗期间保留瘦体重 Bimagrumab（抗激活素抗体）与GLP-1的联合试验正在进行中理想终点：不仅看体重和体成分，更应关注握力、6分钟步行、爬楼梯等功能性指标7.3 胃肠道耐受：持续优化的方向不同GLP-1药物的胃肠道不良事件率差异较大，与药代动力学特征（达峰时间、半衰期）密切相关。更慢的Tmax、更平稳的血药浓度是改善耐受性的关键方向。GIP组分可能通过抗厌恶性作用进一步改善耐受性。7.4 成本与可及性：全球性的挑战以美国定价为例，semaglutide 2.4mg每月费用超过1000美元，tirzepatide类似。这使得全球大多数患者无法负担。小分子口服药物有望通过更低的生产成本和更易扩大的产能缓解这一问题，但定价策略仍将是一个复杂的全球健康公平问题。7.5 特殊人群：数据空白老年人：获益-风险比需要更多数据儿童和青少年：liraglutide和semaglutide已获批用于12+岁肥胖，但长期影响未知妊娠期：安全性数据极度缺乏7.6 个体化医疗：谁最适合哪种药？预测哪些患者对哪种GLP-1药物反应最好的生物标志物和遗传学工具尚不成熟。一项涉及10,960人的多祖先生物样本库分析显示，已知影响体重的多基因评分和GLP-1R相关错义变异均无法预测GLP-1药物的减重效果。这是个体化代谢医学亟待突破的领域。八、未来展望：GLP-1的下一个十年 Drucker教授在综述结尾提出了几个值得深思的未来方向：更强大的药物：25%以上减重效果的药物已不再是科幻。retatrutide、Cagri-Sema等候选药物正在接近这一目标。更便利的给药：每月一次甚至更少频率的注射（MET-097）、每日一次口服小分子、皮下植入物（NPM-115）等多种方案正在探索中。更精准的靶向：通过将功能性分子偶联到GLP-1配体上，实现对特定GLP-1R阳性细胞群的精准调控。更广阔的适应症：外周动脉疾病、神经精神疾病、自身免疫性疾病、甚至1型糖尿病的心脏和肾脏保护——GLP-1的适应症版图仍在快速扩张。新型递送技术：基因和细胞治疗、RNA干扰、甚至基因编辑技术调控GLP-1R信号通路，这些前沿技术可能从根本上改变GLP-1治疗的范式。治疗持久性问题：能否通过一定疗程的治疗实现持续的"代谢记忆"效应，从而使患者在停药后仍长期获益？这或许是未来最重要的研究问题之一。结语 Drucker教授在综述结尾写道："GLP-1发现40年后，新一代药物展现出超越糖尿病和肥胖原始适应症的巨大潜力，有望为人类健康带来实质性改善。" 从1987年鳗鱼基因中的一个意外发现，到2025年改变全球数亿人生活的"万能药"候选，GLP-1的故事是现代药物研发史上最精彩的篇章之一。从降糖到减重，从护心到保肾，从治肝到健脑，GLP-1类药物正在书写着现代医学史上最引人注目的"适应症扩张"传奇。 2025年，这个赛道依然火热，竞争日趋激烈，而真正的赢家——广大的患者——或许才刚刚开始受益。对于医药从业者、投资者和每一位关注健康的人而言，密切关注GLP-1领域的临床进展，无疑是把握未来十年医疗健康趋势的关键一环。参考文献 Drucker DJ. GLP-1-based therapies for diabetes, obesity and beyond. Nat Rev Drug Discov. 2025. doi:10.1038/s41573-025-01183-8 Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221-2232. Perkovic V, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391:109-121. Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-216. Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity. N Engl J Med. 2023;389:514-526. Frias JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503-515. Sanyal AJ, et al. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N Engl J Med. 2024;391:299-310. Malhotra A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391:1193-1205. Wharton S, et al. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. N Engl J Med. 2023. Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes. Lancet. 2023;402:529-544. 本文内容仅供学术交流和医学科普参考，不构成诊疗建议。具体用药请遵医嘱。© 基于 Nature Reviews Drug Discovery 2025 综述整理

2026-06-02

·GlobeNewswire-Health Care

SCIENTURE Receives U.S. Patent Covering REZENOPY™ (Naloxone HCl) Nasal Spray 10 mg, Strengthening Intellectual Property Protection Through 2041

U.S. Naloxone Market: ~$141 million in annual sales and 9.4 million units annually COMMACK, NY, June 02, 2026 (GLOBE NEWSWIRE) -- SCIENTURE HOLDINGS, INC. (NASDAQ: SCNX), a holding company for existing and planned pharmaceutical operating companies focused on providing enhanced value to patients, physicians and caregivers through the development, commercialization, and distribution of novel specialty products that address unmet market needs, today announced that the United States Patent and Trademark Office has granted U.S. Patent No. 12,622,903 B2, patent covering REZENOPY™ (naloxone HCl) Nasal Spray 10 mg, effective May 12, 2026, with an expiry date of February 5, 2041. The patent was issued to Summit Biosciences Inc. (“Summit”), a subsidiary of Kindeva Drug Delivery L.P. As previously disclosed, Scienture, LLC, a wholly owned subsidiary of Scienture Holdings, Inc., entered into a definitive agreement with Summit in March 2025 for the exclusive U.S. commercialization rights to REZENOPY™. Under the terms of the collaboration, Summit will manufacture and commercially supply REZENOPY™. Pending certain commercial obligations, Scienture will own the new drug application (NDA) for REZENOPY™ in its name and be responsible for the sales, marketing and distribution of the product in the U.S. through Scienture’s commercial operations infrastructure. REZENOPY™ received approval from the U.S. Food and Drug Administration (the “FDA”) on April 19, 2024. REZENOPY™ is the highest FDA-approved Dose per Nasal spray for Naloxone in the US market, delivering 10 mg of naloxone HCl in a single-use nasal spray device for the emergency treatment of known or suspected opioid overdose. The product leverages the proven naloxone hydrochloride molecule and familiar nasal spray form factor, while delivering increased effectiveness against potent opioids. According to IQVIA data (MAT January 2026), total annual U.S. naloxone sales reached approximately $141 million, with unit volume of 9.4 million units, underscoring the significant and growing market opportunity. “The issuance of this patent is a substantial milestone for Scienture and a significant validation of our intellectual patent strategy,” commented Narasimhan Mani, President and co-CEO of Scienture. “With intellectual property protection extending through 2041 and our planned commercial launch of REZENOPY™ in mid-July, we are entering an exciting new phase for the product. As the highest-dosage naloxone nasal spray approved by the FDA, REZENOPY™ has the potential to address a critical public health need while creating long-term value for patients, healthcare providers, and our shareholders.” “This patent enhances the value of REZENOPY™ as we advance toward commercialization and supports our strategy to establish a meaningful presence in the naloxone market,” stated Shankar Hariharan, Executive Chairman and co-CEO of Scienture. “The opioid epidemic continues to evolve with the widespread presence of highly potent synthetic opioids, underscoring the need for effective overdose reversal tools. We believe REZENOPY™ offers a differentiated solution, and we look forward to making it available through our commercial and distribution partners in the coming weeks.” About REZENOPY™ REZENOPY™ (naloxone HCl) Nasal Spray 10mg, is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression in adult and pediatric patients. It is intended for immediate administration as emergency therapy in settings where opioids may be present. REZENOPY™ nasal spray is for intranasal use only and is supplied as a carton containing two (2) blister packages each with a single spray device. IMPORTANT SAFETY INFORMATION Administration: REZENOPY™ nasal spray is for intranasal use only. Seek emergency medical care immediately after use. Administer a single spray into one nostril. If the patient does not respond within 2 to 3 minutes or responds and then relapses into respiratory depression, an additional dose may be given into the other nostril with a new device. Do not administer more than 2 sprays per day. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance.Contraindications: REZENOPY™ nasal spray is contraindicated in patients known to be hypersensitive to naloxone hydrochloride or to any of the other ingredients.Warnings and Precautions: Risk of Recurrent Respiratory and CNS Depression: Due to the duration of action of naloxone relative to the opioid, keep the patient under continued surveillance and administer additional doses as necessary while awaiting emergency medical assistance.Risk of Limited Efficacy with Partial Agonists or Mixed Agonists/Antagonists: Reversal of respiratory depression caused by partial agonists or mixed agonists/antagonists, such as buprenorphine and pentazocine, may be incomplete. Larger or repeat doses may be required.Precipitation of Severe Opioid Withdrawal: Use in patients who are opioid-dependent may precipitate opioid withdrawal. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated. Monitor for the development of opioid withdrawal.Risk of Cardiovascular Effects: Abrupt postoperative reversal of opioid depression may result in adverse cardiovascular effects. These events have primarily occurred in patients who had pre-existing cardiovascular disorders or received other drugs that may have similar adverse cardiovascular effects. Monitor these patients closely in an appropriate healthcare setting after use of naloxone hydrochloride. Adverse Reactions: The following adverse reactions were observed in a REZENOPY™ nasal spray clinical study: upper abdominal pain, nasopharyngitis, and dysgeusia.Storage and Handling: Store REZENOPY™ nasal spray in the blister and cartons provided. Store between 2°C to 25°C (36°F to 77°F). Excursions permitted up to 40°C (104°F). Do not freeze or expose to excessive heat above 40°C (104°F). Protect from light. REZENOPY™ nasal spray may freeze at cold temperatures. If this happens, the device will not spray. If REZENOPY™ nasal spray is frozen and is needed in an emergency, do NOT wait for it to thaw; get emergency medical help right away. For more detailed information, please refer to the full prescribing information provided by the FDA. About Scienture Holdings, Inc. SCIENTURE HOLDINGS, INC. (NASDAQ: “SCNX”), through its wholly owned subsidiary, Scienture, LLC, is a comprehensive pharmaceutical product company focused on providing enhanced value to patients, physicians and caregivers by offering novel specialty products to satisfy unmet market needs. Scienture, LLC is a branded, specialty pharmaceutical company consisting of a highly experienced team of industry professionals who are passionate about developing and bringing to market unique specialty products that provide enhanced value to patients and healthcare systems. The assets in development at Scienture are across therapeutics areas, indications and cater to different market segments and channels. For more information please visit: www.scientureholdings.com and www.scienture.com. Cautionary Statements Regarding Forward-Looking Statements This press release contains certain statements that may be deemed to be “forward-looking statements” within the federal securities laws, including the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Statements that are not historical are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements relate to future events or our future performance or future financial condition. These forward-looking statements are not historical facts, but rather are based on current expectations, estimates and projections about our company, our industry, our beliefs and our assumptions. Such forward-looking statements include, but are not limited to, statements regarding our or our management team’s expectations, hopes, beliefs, intentions or strategies regarding the future, including for the products we may launch, such as REZENOPY™, the success those products may have in the marketplace, and our strategies related to those products. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. In some cases, you can identify forward-looking statements by the following words: “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” or the negative of these terms or other similar expressions, but the absence of these words does not mean that a statement is not forward-looking. Forward-looking statements are subject to a number of risks and uncertainties (some of which are beyond our control) that may cause actual results or performance to be materially different from those expressed or implied by such forward-looking statements. Accordingly, readers should not place undue reliance on any forward-looking statements. These risks include risks relating to agreements with third parties; our ability to raise funding in the future, as needed, and the terms of such funding, including potential dilution caused thereby; our ability to continue as a going concern; security interests under certain of our credit arrangements; our ability to maintain the listing of our common stock on the Nasdaq Capital Market; claims relating to alleged violations of intellectual property rights of others; the outcome of any current legal proceedings or future legal proceedings that may be instituted against us; unanticipated difficulties or expenditures relating to our business plan; and those risks detailed in our most recent Annual Report on Form 10-K and subsequent reports filed with the SEC. Forward-looking statements speak only as of the date they are made. Scienture Holdings, Inc. undertakes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise that occur after that date, except as otherwise provided by law. Contact: SCIENTURE HOLDINGS, INC.20 Austin BlvdCommack, NY 11725Phone: (866) 468-6535Email: IR@Scienture.com

引进/卖出上市批准

100 项与丁丙诺啡相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D07132	丁丙诺啡	N07BC01	DB00921

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
阿片相关性障碍	美国	Braeburn, Inc.	2023-05-23
鸦片依赖	欧盟	Camurus AB	2018-11-20
鸦片依赖	冰岛	Camurus AB	2018-11-20
鸦片依赖	列支敦士登	Camurus AB	2018-11-20
鸦片依赖	挪威	Camurus AB	2018-11-20
阿片滥用	美国	Indivior, Inc.	2017-11-30
疼痛	美国	Knoa Pharma LLC	2017-10-13
慢性疼痛	美国	Knoa Pharma LLC	2010-06-30

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适应症	最高研发状态	国家/地区	公司	日期
镇痛	临床3期	-	Purdue Pharma LP	2011-11-01
术后疼痛	临床3期	-	Purdue Pharma LP	2011-11-01
椎间盘疾病	临床3期	中国	萌蒂（中国）制药有限公司	2009-08-01
肌肉骨骼疼痛	临床3期	中国	萌蒂（中国）制药有限公司	2009-08-01
阿片类药物依赖美沙酮	临床3期	美国	Titan Pharmaceuticals, Inc.	2008-09-01
脊椎骨关节炎	临床3期	美国	Purdue Pharma LP	2004-04-01
膝关节炎	临床3期	美国	Purdue Pharma LP	1999-06-01
腰痛	临床3期	美国	Purdue Pharma LP	1997-04-01
骨关节炎	临床3期	美国	Purdue Pharma LP	1996-11-01
肠易激综合征	临床2期	美国	OrphoMed, Inc.	2019-11-22

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03918850 (MOMs, CTgov)	临床3期	阿片相关性障碍 \| 阿片滥用 \| 新生儿戒断综合征 ... 更多	140	Buprenorphine Injection (BUP-XR)	憲繭積製壓顧構鏇艱壓(膚鏇製鬱選願鏇艱襯淵) = 遞淵膚築鹹選獵繭構選鬱壓鑰構製觸鹹淵糧蓋 (築齋觸觸衊窪遞鬱餘製, 4.2) 更多	-	2026-06-04
				Buprenorphine Sublingual Product (BUP-SL)	憲繭積製壓顧構鏇艱壓(膚鏇製鬱選願鏇艱襯淵) = 顧膚糧築獵襯顧選膚鹹鬱壓鑰構製觸鹹淵糧蓋 (築齋觸觸衊窪遞鬱餘製, 4.2) 更多
NCT03918850 (Pubmed \| JAMA Intern Med)	临床3期	阿片滥用	140	Extended-release buprenorphine	鹹觸鹹獵範鹹襯艱鬱顧(簾構願築齋繭繭鹽繭窪) = 製鬱積齋糧夢製壓糧獵夢糧醖襯範築餘衊襯淵 (醖構餘壓齋積積顧積範 ) 更多	积极	2026-05-01
				Sublingual buprenorphine	鹹觸鹹獵範鹹襯艱鬱顧(簾構願築齋繭繭鹽繭窪) = 淵齋壓夢艱鹹範積鬱窪夢糧醖襯範築餘衊襯淵 (醖構餘壓齋積積顧積範 ) 更多
NCT04677114 (BOPAT, CTgov)	临床2期	阿片相关性障碍 \| 阿片滥用 \| 感染	71	care antibiotic treatment+Buprenorphine	衊膚獵廠齋願鹽憲鬱鹹 = 觸網窪範顧網鑰鏇壓築壓蓋鑰選鑰鏇積憲遞糧 (鏇蓋衊膚艱鹹鑰願廠築, 餘遞範積積鹽衊憲鹹築 ~ 築壓觸膚壓獵襯鏇艱觸) 更多	-	2026-03-27
NCT04225598 (Pubmed \| JAMA)	临床2期	阿片滥用	1,994	Extended-release buprenorphine	構網餘憲遞蓋餘夢願選(齋襯衊壓築製網範醖鑰) = 鹽網窪廠網衊願獵廠憲艱鬱簾襯簾願襯窪範願 (膚鹹淵壓願窪襯鑰艱鬱 ) 更多	相似	2026-03-17
				Sublingual buprenorphine	構網餘憲遞蓋餘夢願選(齋襯衊壓築製網範醖鑰) = 鬱觸獵窪網淵憲蓋顧艱艱鬱簾襯簾願襯窪範願 (膚鹹淵壓願窪襯鑰艱鬱 ) 更多
NCT04995029 (CTgov)	临床4期	阿片相关性障碍 \| 阿片滥用	785	Extended-release Buprenorphine (Maintenance Phase: Extended-release Buprenorphine 100 mg)	壓鏇鬱餘夢鹹壓積繭構 = 齋願蓋憲鬱繭鑰遞製願艱齋積築鏇鏇觸願選獵 (淵鬱艱廠鹽選範蓋蓋夢, 獵餘蓋範窪鏇壓壓艱窪 ~ 艱簾構積築製憲築窪糧) 更多	-	2025-09-25
				Extended-release Buprenorphine (Maintenance Phase: Extended-release Buprenorphine 300 mg)	壓鏇鬱餘夢鹹壓積繭構 = 築淵鑰廠淵製願襯範衊艱齋積築鏇鏇觸願選獵 (淵鬱艱廠鹽選範蓋蓋夢, 夢製獵繭窪繭觸繭積顧 ~ 網餘憲夢繭顧鹹鬱鏇憲) 更多
NCT04454411 (CTgov)	临床2期	阿片滥用 \| 鸦片依赖	3	Brixadi (Buprenorphine)	鑰遞願積繭網鹽構願製(壓憲糧網鹽壓選憲憲襯) = 鏇繭鏇衊壓選構顧夢築鹽構鬱選鬱範製廠積醖 (膚醖膚衊範夢鹹築艱選, 鏇廠膚鬱糧鏇鏇淵製衊 ~ 鹽選鹹願膚艱遞夢壓壓) 更多	-	2025-08-06
				Vivitrol (Naltrexone)	鑰遞願積繭網鹽構願製(壓憲糧網鹽壓選憲憲襯) = 醖膚簾壓鬱鏇糧簾鹽選鹽構鬱選鬱範製廠積醖 (膚醖膚衊範夢鹹築艱選, 廠鑰糧顧醖襯憲艱構鏇 ~ 鏇鏇壓鹹觸憲餘壓齋廠) 更多
NCT04995029 (NEWS)	临床4期	阿片相关性障碍	729	丁丙诺啡-RBP-6000	獵齋襯艱遞鏇網餘積製(簾蓋憲糧獵顧夢獵築顧) = 選齋網餘網願艱選餘鑰繭糧築壓齋鹹遞鑰築鑰 (範鬱蓋獵鹽餘鹽窪遞膚 )	优效	2024-11-19
				丁丙诺啡-RBP-6000（fentanyl-positive）	獵齋襯艱遞鏇網餘積製(簾蓋憲糧獵顧夢獵築顧) = 淵鑰選鬱鬱鏇壓構鹽窪繭糧築壓齋鹹遞鑰築鑰 (範鬱蓋獵鹽餘鹽窪遞膚 )
NCT02651584 (PRNewswire) 人工标引	临床3期	阿片相关性障碍	123	BRIXADI (fentanyl-positive)	餘淵膚繭遞獵夢鑰觸願(鏇醖選鑰繭鹹窪壓艱築) = 願選鬱齋積築遞選夢構鏇網蓋鑰願壓蓋網遞齋 (壓糧鬱獵鹽顧鑰鑰窪獵 ) 更多	积极	2024-06-25
				buprenorphine + naloxone (fentanyl-positive)	餘淵膚繭遞獵夢鑰觸願(鏇醖選鑰繭鹹窪壓艱築) = 壓鹹廠淵廠糧壓簾壓願鏇網蓋鑰願壓蓋網遞齋 (壓糧鬱獵鹽顧鑰鑰窪獵 ) 更多
NCT02651584 (Pubmed \| JAMA Netw Open)	临床3期	fentanyl-positive \| norfentanyl	428	Subcutaneous Buprenorphine	遞願夢鑰積製窪獵憲夢(夢糧願夢夢壓鏇簾構衊) = 餘願膚艱觸築網鏇餘蓋築衊醖顧壓鑰齋遞鑰築 (顧衊淵餘糧廠願餘鑰網 )	积极	2024-06-03
				Sublingual Buprenorphine-Naloxone	遞願夢鑰積製窪獵憲夢(夢糧願夢夢壓鏇簾構衊) = 衊蓋繭醖憲襯鹹觸齋醖築衊醖顧壓鑰齋遞鑰築 (顧衊淵餘糧廠願餘鑰網 )
NCT02357901 \| NCT02510014 \| NCT02896296 (phase 3 studies, Pubmed \| J Subst Use Addict Treat)	临床3期	阿片滥用	916	BUP-XR 300 mg × 2	顧願廠簾鏇艱淵廠範積(衊齋積夢廠積築膚齋鬱) = low incidence 夢願構選醖憲夢遞襯鹽 (選襯齋鏇鹹鹽餘艱鏇鬱 ) 更多	积极	2023-11-01
				BUP-XR 100 mg × 4