Bupropion Hydrochloride

Late-breaking oral presentation of results from the positive pivotal ACCORD-2 Phase 3 trial of AXS-05 in Alzheimer’s disease agitation Presentation featuring network meta-analysis of SYMBRAVO® versus oral CGRPs NEW YORK, April 04, 2025 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) disorders, today announced multiple presentations spanning its innovative, industry-leading psychiatry and neurology portfolio at the 2025 American Academy of Neurology (AAN) Annual Meeting, being held April 5-9 in San Diego, California. Oral and poster presentations include data from the positive pivotal ACCORD-2 Phase 3 trial of AXS-05 in Alzheimer’s disease (AD) agitation, accepted as a late-breaking abstract, and from the positive pivotal SYMPHONY Phase 3 trial of AXS-12 in narcolepsy. Additional data being presented includes a network meta-analysis comparing the efficacy of SYMBRAVO® (AXS-07) to oral CGRPs in the acute treatment of migraine. Details for the presentations are as follows: Alzheimer’s Disease Agitation Title: Efficacy and Safety of AXS-05 in Alzheimer's Disease Agitation: A Phase 3 Randomized Withdrawal Double-Blind Placebo-Controlled Study Oral Presentation Date and Time: Monday, April 7, 11:27 - 11:33 a.m. PT Poster Presentation Date and Time: Monday, April 7, 12:09 - 12:45 p.m. PT Session Name: Late-breaking Science 1 Poster Number: 3 Abstract: 246 Narcolepsy Title: AXS-12 for the Treatment of Narcolepsy: Topline Results from the Phase 3 SYMPHONY Trial Oral Presentation Date and Time: Tuesday, April 8, 10:45 - 11 a.m. PT Lead Author: Michael J. Thorpy, MD, Director of the Sleep-Wake Disorders Center at the Montefiore Medical Center and Professor of Neurology at Albert Einstein College of Medicine, New York, NY Session Name: Clinical Trials Plenary Session Program Number: PL5 Title: CRESCENDO: Results from a Survey of Symptom Burden and Quality of Life in Patients with Narcolepsy Type 1 Poster Presentation Date and Time: Tuesday, April 8, 8 - 9 a.m. PT Lead Author: Michael J. Thorpy, MD, Director of the Sleep-Wake Disorders Center at the Montefiore Medical Center and Professor of Neurology at Albert Einstein College of Medicine, New York, NY Session Name: Sleep 2 Program Number: P8:001 Migraine Title: Comparative Efficacy of AXS-07 vs. Gepants for Acute Treatment of Migraine: A Network Meta-Analysis Poster Presentation Date and Time: Tuesday, April 8, 5 - 6 p.m. PT Lead Author: Stephanie Nahas, MD, Associate Professor of Neurology at the Thomas Jefferson University Hospitals-Jefferson Health Center, Philadelphia, PA Session Name: Headache: Advances in CGRP Inhibitors and Migraine 3 Program Number: P10.006 About SYMBRAVO SYMBRAVO is a novel, oral, single-dose medicine approved for the acute treatment of migraine with or without aura in adults. SYMBRAVO consists of MoSEIC™ meloxicam and rizatriptan. Meloxicam is a new molecular entity for migraine enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which enables the rapid absorption of meloxicam while maintaining a long plasma half-life. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug (NSAID) and rizatriptan is a 5-HT1B/1D agonist. SYMBRAVO is designed to provide rapid, enhanced, and consistent migraine pain relief, and reduced symptom recurrence. The exact mechanism of action of SYMBRAVO in the treatment of acute migraine is unknown. For more information, visit www.symbravo.com. INDICATION AND IMPORTANT SAFETY INFORMATION What is SYMBRAVO (sim-BRAH-voh)? SYMBRAVO is a combination of meloxicam (an NSAID) and rizatriptan (a triptan). SYMBRAVO is an oral prescription medicine used to treat acute migraine headaches with or without aura in adults. SYMBRAVO is not used to prevent or decrease the number of migraine headaches you have or for treatment of hemiplegic or basilar migraines. SYMBRAVO is not indicated as a treatment for cluster headaches or for use in children. WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT SYMBRAVO? SYMBRAVO may increase the risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase with increasing doses, and longer use, of NSAIDs. Do not take SYMBRAVO right before or after a heart surgery called a “coronary artery bypass graft” (CABG). Avoid taking SYMBRAVO after a recent heart attack unless your healthcare provider (HCP) tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack. Stop taking SYMBRAVO and get emergency help right away if you have any of the following symptoms which can be indicative of a heart attack or stroke: discomfort in your chest that lasts for more than a few minutes, or that goes away and comes back breaking out in a cold sweat nausea or vomiting feeling lightheaded severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw weakness in one part or one side of your body pain or discomfort in your arms, back, neck, jaw, or stomach slurred speech shortness of breath with or without chest discomfort People with risk factors for heart disease should not take SYMBRAVO unless a heart exam is done and shows no problem. You have higher risk for heart disease if you: have high blood pressure smoke have high cholesterol are overweight have diabetes or a family history of diabetes SYMBRAVO can increase the risk of potentially life-threatening bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach, and intestines that can occur anytime during use and without warning symptoms. SYMBRAVO may cause serious allergic or skin reactions which can be life-threatening. Stop taking SYMBRAVO and get emergency help right away if you develop: sudden wheezing or problems breathing or swallowing blisters or bleeding of your lips, eye lids, mouth, nose, or genitals rash or reddening of your skin with blisters or peeling swelling of your lips, tongue, throat or body fainting SYMBRAVO already contains an NSAID (meloxicam). Do not use SYMBRAVO with other medicines to lessen pain or fever or with other medicines for colds or sleeping problems without talking to your HCP first, because they may contain an NSAID also. Do not take SYMBRAVO if you: have or had heart problems or right before or after heart bypass surgery have or had a stroke or transient ischemic attack (TIA) take an antidepressant medicine called monoamine oxidase inhibitor (MAOI) or have taken a MAOI within the last 2 weeks have or had blood vessel problems of your legs and arms, stomach (ischemic bowel disease), or kidneys are allergic to meloxicam, rizatriptan, NSAIDs, or any of the ingredients in SYMBRAVO have or had hemiplegic or basilar migraines have uncontrolled high blood pressure have had an asthma attack, hives, or other allergic reaction after taking aspirin or any other NSAIDs take propranolol containing medicines have taken other triptan or ergot-containing medicines within the last 24 hours have moderate to severe kidney problems and are at risk of kidney failure or if you are on dialysis SYMBRAVO may cause serious side effects. These serious side effects include: heartbeats that are too fast or too slow (arrhythmias) liver or kidney problems including organ failure new or worse high blood pressure low red blood cell count (anemia) heart failure life-threatening skin reactions asthma attacks in people who have asthma Medication Overuse Headaches: Some people who use too many SYMBRAVO tablets may have worse headaches. If your headaches get worse, your HCP may decide to stop your treatment with SYMBRAVO. Stop taking SYMBRAVO and get emergency help right away if you have any of the following: Stomach and intestinal problems. Symptoms of gastrointestinal and colonic ischemic events may include sudden or severe stomach pains even after meals; sudden weight loss; severe nausea, vomiting, constipation, diarrhea; and bloody diarrhea. Circulation problems to legs and feet. Symptoms of peripheral vascular ischemia may include cramping and pain in your legs and hips; heaviness or tightness in leg muscles; burning, aching, numbness, tingling, or weakness in your legs, feet, or toes; cold feelings or color changes in one or both legs or feet. Serotonin syndrome. Can happen when taking SYMBRAVO with antidepressant medicines called SSRIs or SNRIs. Stop taking SYMBRAVO and call your doctor right away if you have any of the following symptoms: mental status changes including agitation, hallucinations, or coma fast heartbeat changes in your blood pressure increased body temperature tight muscles trouble walking mental status changes including agitation, hallucinations, or coma fast heartbeat changes in your blood pressure increased body temperature tight muscles trouble walking Stop taking SYMBRAVO and call your healthcare provider right away if you have any of the following symptoms: nausea vomiting blood more tired or weaker than usual blood in your bowel movement or it is black and sticky like tar diarrhea itching, skin rash, or blisters with fever unusual weight gain your skin or eyes look yellow indigestion or stomach pain swelling of the arms, legs, hands, or feet flu-like symptoms tenderness in your right upper side vision problems COMMON SIDE EFFECTS The most common side effects of SYMBRAVO include dizziness and tiredness. These are not all the possible side effects of SYMBRAVO. Tell your doctor if you have any side effects. You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1–800-FDA-1088. BEFORE USING Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. It is important to tell your HCP if you are taking: Propranolol containing medicines such as Inderal® LA or Innopran® XL Aspirin or other anti-coagulants (blood thinners) Medicines to help your mood including SSRIs and SNRIs If you are unsure if you take any of these medicines, ask your HCP. They can tell you if it is safe to take SYMBRAVO with your other medicines. Tell your HCP if you are pregnant or plan to become pregnant. SYMBRAVO is not recommended during pregnancy. Taking NSAIDs, including SYMBRAVO, at about 20 weeks of pregnancy or later may harm your unborn baby. NSAIDs, including SYMBRAVO, should not be taken after about 30 weeks of pregnancy. Tell your HCP if you are breastfeeding or plan to breastfeed. Propranolol containing medicines such as Inderal® LA or Innopran® XL Aspirin or other anti-coagulants (blood thinners) Medicines to help your mood including SSRIs and SNRIs Tell your HCP about all your medical conditions, including if you: have or have had heart problems, high blood pressure, chest pain, or shortness of breath have any risk factors for heart or blood vessel problems have kidney or liver problems have asthma Review the list below with your HCP. SYMBRAVO may not be right for you if: take daily preventative aspirin you are pregnant or plan to become pregnant you are breastfeeding or plan to breastfeed HOW TO TAKE SYMBRAVO is available by prescription only. Take SYMBRAVO exactly as instructed by your HCP. The maximum daily dose of SYMBRAVO is 1 tablet. Talk to your HCP about what to do if your headache does not go away or comes back. Take SYMBRAVO for the shortest time needed. Swallow SYMBRAVO tablets whole. Do not crush, chew, or divide the tablets. SYMBRAVO can be taken with or without food. Do not give SYMBRAVO to other people. If you take too much SYMBRAVO call your poison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away. LEARN MORE For more information about SYMBRAVO, call 866-496-2976 or visit SYMBRAVO.com. This summary provides basic information about SYMBRAVO but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other HCP about SYMBRAVO and how to take it. Your HCP is the best person to help you decide if SYMBRAVO is right for you. SYM CON BS 01/2025 Please see full Prescribing Information, including Boxed Warning for risk of serious cardiovascular and gastrointestinal adverse events, and Medication Guide. About AXS-05 AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor under development for the treatment of Alzheimer’s disease (AD) agitation and smoking cessation. AXS-05 utilizes a proprietary formulation and dose of dextromethorphan and bupropion, and Axsome’s metabolic inhibition technology, to modulate the delivery of the components. The dextromethorphan component of AXS-05 is an uncompetitive NMDA receptor antagonist, also known as a glutamate receptor modulator, and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan and is a norepinephrine and dopamine reuptake inhibitor. AXS-05 is covered by a robust patent estate extending out to at least 2043. AXS-05 was granted U.S. FDA Breakthrough Therapy designation for the treatment of Alzheimer’s disease agitation in June 2020. About AXS-12 AXS-12 (reboxetine) is a highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulator under development for the treatment of narcolepsy. AXS-12 is thought to modulate noradrenergic activity to promote maintain tone during wakefulness, and noradrenergic and cortical dopamine signaling to promote wakefulness and enhance cognition. AXS-12 has been granted U.S. Food and Drug Administration (FDA) Orphan Drug Designation for the treatment of narcolepsy. AXS-12 is covered by issued patents providing protection to at least 2039. AXS-12 is an investigational drug product not approved by the FDA. About Axsome Therapeutics Axsome Therapeutics is a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) conditions. We deliver scientific breakthroughs by identifying critical gaps in care and develop differentiated products with a focus on novel mechanisms of action that enable meaningful advancements in patient outcomes. Our industry-leading neuroscience portfolio includes FDA-approved treatments for major depressive disorder, excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea, and migraine, and multiple late-stage development programs addressing a broad range of serious neurological and psychiatric conditions that impact over 150 million people in the United States. Together, we are on a mission to solve some of the brain’s biggest problems so patients and their loved ones can flourish. For more information, please visit the Company’s website at www.axsome.com. Forward Looking Statements Certain matters discussed in this press release are “forward-looking statements”. The Company may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the commercial success of the Company’s Sunosi®, Auvelity®, and Symbravo® products and the success of the Company’s efforts to obtain any additional indication(s) with respect to solriamfetol and/or AXS-05; the Company’s ability to maintain and expand payer coverage; the success, timing and cost of the Company’s ongoing clinical trials and anticipated clinical trials for the Company’s current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including the Company’s ability to fully fund the Company’s disclosed clinical trials, which assumes no material changes to the Company’s currently projected revenues or expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of the Company’s ongoing clinical trials, and/or data readouts, and the number or type of studies or nature of results necessary to support the filing of a new drug application (“NDA”) for any of the Company’s current product candidates; the Company’s ability to fund additional clinical trials to continue the advancement of the Company’s product candidates; the timing of and the Company’s ability to obtain and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory authority approval of, or other action with respect to, the Company’s product candidates, including statements regarding the timing of any NDA submission; the Company’s ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the Company, if at all; the successful implementation of the Company’s research and development programs and collaborations; the success of the Company’s license agreements; the acceptance by the market of the Company’s products and product candidates, if approved; the Company’s anticipated capital requirements, including the amount of capital required for the commercialization of Sunosi, Auvelity, and Symbravo and for the Company’s commercial launch of its other product candidates, if approved, and the potential impact on the Company’s anticipated cash runway; the Company’s ability to convert sales to recognized revenue and maintain a favorable gross to net sales; unforeseen circumstances or other disruptions to normal business operations arising from or related to domestic political climate, geo-political conflicts or a global pandemic and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstance. Investors: Mark Jacobson Chief Operating Officer (212) 332-3243 mjacobson@axsome.com Media: Darren Opland Director, Corporate Communications (929) 837-1065 dopland@axsome.com Source: Axsome Therapeutics, Inc.

点击“蓝字”关注我们编者按：肥胖已成为全球性公共卫生挑战，近年来其管理引发高度关注。生活方式干预是长期体重管理的基石，无论是强化治疗期还是治疗维持期。然而，知易行难，生活方式干预效果往往不理想，且难以长期坚持。随着全球肥胖发病率的快速增长，新型减重药物不断问世，为肥胖管理提供了更多选择。那么，为何生活方式干预难以持续？联合药物治疗怎样发挥“增效器”作用？如何构建减重的“药物+行为管理”整合路径？胰高糖素样肽-1受体激动剂（GLP-1RA）周制剂司美格鲁肽减重效果如何？本期大咖谈，东南大学附属中大医院王尧教授将围绕这些问题进行深入解析。王尧 教授东南大学附属中大医院内分泌科主任医师，教授，博士生导师中华预防医学会糖尿病预防与控制专业委员会委员中华医学会内分泌学分会脂代谢学组委员中华医学会糖尿病学分会糖尿病监测与治疗新技术学组委员江苏省医学会糖尿病学分会委员江苏省中西医结合内分泌分会常委江苏省中西医结合糖尿病一体化诊疗分会常委江苏省医学会糖尿病学分会肥胖学组成员主持国家自然科学基金和江苏省自然科学基金面上项目以及科技部重大专项子课题，在Diabetes、Diabetologia、Metabolism等期刊发表SCI论文50余篇，对糖尿病胰岛功能损伤的分子机制和肥胖的防治以及内分泌代谢病发病理论有较深入的研究和临床经验。《国际糖尿病》生活方式干预作为肥胖管理基石被广泛推荐，但现实中常面临效果难以持续的问题。您如何评价生活方式干预效果？其主要瓶颈有哪些？背后原因是什么？王尧教授饮食或运动干预统称为生活方式干预或行为干预，因其成本低、安全性好，作为体重管理的基本方法被广泛采用，但减重效果有限。一项系统综述[1]回顾了8项前瞻性研究，生活方式干预期间均实现减重>5%且随访>3年。结果显示，成人肥胖患者单纯生活方式管理的平均减重幅度为7.4%，但干预期结束后第2年体重即开始回升，大约4.1年时恢复到减重前的基线水平。因此，对于长期体重管理来说，单纯生活方式干预存在一定瓶颈，主要体现在以下两方面：长期依从性低：长期遵循饮食和运动干预考验个体自我约束和监督能力，受生活环境、心理状态、社会支持等多因素影响[2]。比如，在毅力方面，当体重下降未达预期时，个人会感到沮丧，失去动力；在时间方面，因缺乏时间、时间管理不善或组织困难，无法长期改变生活方式；在健康和身体状况方面，很多患者合并多种慢性疾病，如心肝肺功能异常、关节或脊柱损伤、高血压、高血糖等，这些是改变生活方式的突出障碍；另外，社会经济制约、对减重认知不足、缺乏运动乐趣等都会导致无法坚持长期生活方式管理。体重下降平台期出现早：由于体内代谢适应的存在，人体在减重过程中为恢复能量平衡而触发一系列生理和内分泌调整，比如瘦素和甲状腺激素水平下降、饥饿素水平上升等，进而降低能量消耗、促进能量储存，同时增强食欲，这些因素作用下会共同抵抗体重减轻，使减重出现平台期，这也是人体内的一种自我保护机制[3]。《国际糖尿病》近年研究显示药物治疗可显著提升生活方式干预效果，从代谢调控角度，药物如何突破单纯行为干预的生物学限制？王尧教授目前的减重药物研发日新月异，它们通过调控食欲中枢、脂肪代谢、胰岛素敏感性等靶点进行精准干预，有效突破单纯生活方式干预所面临的代谢适应和能量补偿的瓶颈，进而调控体重。具体来说：通过食欲中枢调控，突破饥饿信号的生物学抵抗：单纯生活方式干预常因下丘脑弓状核的负反馈调节而失效。目前研发的具有减重作用的药物中，比如GLP-1RA可激活下丘脑POMC神经元，抑制NPY/AgRP神经元，降低饥饿感并延长饱腹感[4]；GIP/GLP-1双受体激动剂同时激活GLP-1和GIP受体，协同增强下丘脑能量平衡调控[5]。通过脂肪代谢重编程，打破能量储存的代谢惯性：单纯饮食控制难以逆转脂肪组织的代谢灵活性下降，而药物如MC4R激动剂可靶向瘦素-黑皮质素通路，修复遗传性肥胖患者的能量消耗缺陷，使POMC缺陷患者体重明显下降[6]；β3肾上腺素受体激动剂通过激活UCP1增加脂肪产热，提高基础代谢率[7]。通过调控胰岛素敏感性与优化脂质代谢：胰岛素抵抗是行为干预失败的关键因素之一，而药物可通过多靶点予以改善。比如，SGLT2抑制剂促进尿糖排泄，迫使脂肪组织分解供能，减少内脏脂肪，降低体重[8]；二甲双胍可能通过作用于PEN2，激活AMPK，改善肌肉、脂肪及肝脏的能量代谢[9]。《国际糖尿病》在构建减重的“药物+行为管理”整合路径时，临床实践中应如何把握药物介入时机与行为干预的协同节奏？王尧教授如何将药物治疗和行为干预精准结合，是临床工作中面临的一个实际问题。一般来说，我们会根据国内外指南对患者实行分层管理，并进行动态评估以及阶段性目标设定，从而实现药物和行为干预的精准协同，最终提高减重治疗的长期成功率。首先，风险分层是最主要的，根据患者的体重状态及并发症情况进行评估。针对体重指数（BMI）≥30 kg/m2或BMI≥27 kg/m2合并肥胖相关并发症的患者，建议早期启动药物与行为干预的联合治疗[10]；对于尚处于超重且无合并症的患者，也可在生活方式干预效果不佳如3个月减重<5%或未达预期后，尽早联合减重药物治疗[11]。其次，动态评估代谢状态及行为依从性。整个体重管理过程中，要定期记录患者的饮食日记，通过监测饥饿素、瘦素等激素水平及生化指标变化，识别是否存在生理性饥饿抵抗或行为依从性不足，作为及时进行药物介入的参考[12]。第三，药物介入与行为干预协同的阶段性管理：①行为干预先行（0~3个月）：旨在建立饮食/运动习惯，评估患者的自我管理能力。通过结构化教育、认知行为疗法纠正进食障碍，并为后期的药物介入提供基础。②药物强化期（3~6个月）：旨在突破代谢平台期，增强患者信心。选择GLP-1RA（如司美格鲁肽）或双通道抑制剂（如纳曲酮/安非他酮）等减重药物，同步进行每周一次的行为反馈（如APP打卡或门诊随访）。③长期维持期（6个月后）：旨在逐步减少药物依赖，巩固行为模式。根据患者的体重维持情况调整药物剂量，同时做好长期的体重管理和监测计划。总之，体重管理非常强调个体化原则。对于年轻、并发症较少或仅存在并发症风险的患者，首要目标应设立为3~6个月减重10%~15%，以尽快实现并发症改善及并发症风险降低，同时帮助患者建立减重信心，提高后续减重治疗的依从性。对于年龄较大、并发症较多的患者，更多的是要考虑减重的安全性，可以设立相对较为缓慢的减重目标，比如3~6个月减重5%~10%，以平稳减重，尽量避免不必要的并发症发生。减重目标设立及减重方案实施的过程中，还需注意：①避免行为干预被药物替代：需强调药物干预是生活方式干预的“增效剂”，而非替代方案；②动态监测与反馈减重效果：每3个月评估体重、体成分、生化指标及心理状态，及时调整方案；③个体化停药计划：GLP-1类药物需缓慢减量，避免反弹，可联合认知重塑训练等以降低复胖风险。在长期体重管理中，减重后的体重维持极具挑战性。《国际糖尿病》以GLP-1RA周制剂司美格鲁肽为例，其在生活方式干预增效中的独特价值体现在哪些方面？王尧教授GLP-1RA司美格鲁肽作为减重市场上一个非常重要的药物目前备受宠爱，其独特作用受到广大医护人员及患者的关注。从作用机制来看，司美格鲁肽是一种多靶点调控药物，其通过激活下丘脑弓状核的GLP-1受体，减少饥饿感，发挥中枢效应[13]；通过延缓胃排空，发挥外周效应[14]；通过促进棕色脂肪组织产热，发挥代谢效应[15]。而且，司美格鲁肽在减重方面积累了丰富的临床研究证据，其在上市前开展了全球多中心3期临床试验STEP系列研究，纳入不同地区、不同人种、不同性别、不同年龄及不同类型的肥胖患者。结果证实，不论是超重还是肥胖患者，不论是否合并2型糖尿病，在生活方式干预的基础上，司美格鲁肽均可起到较好且稳定的减重效果，减重幅度达9.6%~17.4%，减重效果持续至少2年，且具有良好的安全性和耐受性[16-22]。同时，司美格鲁肽还具有心血管和肾脏的保护机制，已被证实具有心血管和肾脏获益。结语：生活方式干预是长期体重管理的基石，包括饮食管理、运动干预、习惯养成和社会心理支持等。值得注意的是，针对肥胖的生活方式干预具有高度个体化的特点，患者的依从性以及人体自身的代谢适应对于干预效果影响颇大。而药物干预是生活方式干预的“增效剂”，其中司美格鲁肽周制剂是一个非常出色的体重管理药物，通过多靶点调控机制提高减重效率，实现长期体重管理成功率的显著提升。参考文献（上下滑动可查看）1. Nordmo M, et al. Obes Rev. 2020; 21(1): e12949.2. Burgess E, et al. Clin Obes. 2017; 7(3): 123-135.3. Martínez-Gómez MG, Roberts BM. J Strength Cond Res. 2022; 36(10): 2970-2981.4. Secher A, et al. J Clin Invest. 2014; 124(10): 4473-4488.5. Campbell JE. Mol Metab. 2021; 46: 101139.6. Roth CL, et al. Lancet Diabetes Endocrinol. 2024; 12(6): 380-389.7. Cypess AM, et al. Cell Metab. 2015; 21(1): 33-38.8. Pereira MJ, Drugs. 2019; 79(3): 219-230.9.《二甲双胍临床应用专家共识》更新专家组. 中华内科杂志. 2023; 62(6): 619-630.10. American Diabetes Association Professional Practice Committee. Diabetes Care. 2025; 48 (Suppl 1): S167-S180.11. 中华医学会内分泌学分会. 中华内分泌代谢杂志. 2024; 40(7): 545-564.12. Heymsfield SB, Wadden TA. N Engl J Med. 2017; 376(3): 254-266.13. Blundell J, et al. Diabetes Obes Metab. 2017; 19(9): 1242-1251.14. Maselli DB, Camilleri M. Adv Exp Med Biol. 2021; 1307: 171-192.15. Martins FF, et al. Cell Biochem Funct. 2022; 40(8): 903-913.16. Wilding JPH, et al. N Engl J Med. 2021; 384(11): 989-1002. STEP 117. Davies M, et al. Lancet. 2021; 397(10278): 971-984. STEP 218. Wadden TA, et al. JAMA. 2021; 325(14): 1403-1413. STEP 319. Rubino D, et al. JAMA. 2021; 325(14): 1414-1425. STEP 420. Garvey WT, et al. Nat Med. 2022; 28(10): 2083-2091. STEP 521. Kadowaki T, et al. Lancet Diabetes Endocrinol. 2022; 10(3): 193-206. STEP 622. Mu Y, et al. Lancet Diabetes Endocrinol. 2024; 12(3): 184-195. STEP 7声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！（来源：《国际糖尿病》编辑部）版权声明版权属《国际糖尿病》所有。欢迎个人转发分享。其他任何媒体、网站未经授权，禁止转载。