Bioequivalence of Survodutide (BI 456906) When Administered Via Pre-filled Syringe (Formulation A) and Vial (Formulation B2) in Male and Female Trial Participants Who Are Healthy or Otherwise Healthy But Overweight/Obese (an Open-label, Randomised, Single-dose, Two-period, Two-sequence Crossover Trial)

The main objective of this trial is to establish the bioequivalence of survodutide in a pre-filled syringe (reference product [formulation A]) and in a vial (test product [formulation B2]) in male and female trial participants who are healthy or otherwise healthy with overweight/obesity, following subcutaneous administration.

开始日期2026-09-01

申办/合作机构

Boehringer Ingelheim GmbH

NCT07754461

/ Recruiting临床3期

A Phase III, Randomised, Double-blind, Parallel-group, 56-week Study, Evaluating the Efficacy and Safety of Survodutide (BI 456906), Compared With Placebo, in Participants With Type 2 Diabetes, as an Adjunct to Diet and Physical Activity Alone or in Combination With Either Oral Antidiabetic Medications or Insulin

This study aims to find out whether a study medicine called survodutide helps people control their blood sugar. Adults who live with type 2 diabetes and with a body mass index (BMI) of 23 kg/m2 or higher can join.
The study has 3 parts. In each part the study compares survodutide with placebo. Survodutide is being developed to treat several health problems including type 2 diabetes. Placebo looks like survodutide but does not contain any medicine.
Depending on a person's diabetes treatment, a person will be assigned either to
* Part A: healthy eating and physical activity
* Part B: diabetes tablets (no injection of insulin)
* Part C: injection of insulin (with or without diabetes tablets)
Participants are randomly put into 1 of 3 groups, which means the group is chosen by chance. Two groups of participants get survodutide at different dose levels, and the third group gets placebo as injection under the skin once a week. You have a 2 in 3 chance of getting survodutide. During the study, participants continue their regular diabetes treatment.
Participants are in the study for about 1 year and 2 months. During this time, they attend up to 12 visits at the site and receive at least 9 phone calls. Study doctors regularly test participants' blood sugar by checking their HbA1c values and other laboratory test results. The study doctor also regularly checks participants' health and takes note of any changes. For each study part, the results will be compared between the survodutide and the placebo group to see whether the treatment works.

开始日期2026-08-24

申办/合作机构

Boehringer Ingelheim GmbH

CTIS2025-524135-39-00

/ Not yet recruiting临床1期

A study in healthy people or otherwise healthy but overweight or obese to compare 2 formulations of survodutide given in different ways, either as a pre-filled syringe or a pen-like injector

开始日期2026-06-01

申办/合作机构

Boehringer Ingelheim GmbH

100 项与索弗度肽相关的临床结果

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100 项与索弗度肽相关的转化医学

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100 项与索弗度肽相关的专利（医药）

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项与索弗度肽相关的文献（医药）

2026-08-01·DIABETES OBESITY & METABOLISM

Survodutide for the Treatment of Obesity Disease in Japanese Participants: Rationale, Design and Baseline Characteristics of the Phase 3 SYNCHRONIZE ‐ JP Trial

Article

作者: Yamauchi, Toshimasa ; Borowska, Luiza ; Ogawa, Wataru ; Yokote, Koutaro ; Kato, Marie ; Brueckmann, Martina ; Inoue, Takayoshi ; Yan, Shijia ; Takatsuka, Yoji ; Fukushima, Yasushi

ABSTRACT:

Aims:

There is an unmet need for effective pharmacotherapy for obesity disease management in Japan. Survodutide is a novel glucagon receptor/glucagon‐like peptide‐1 receptor (GLP‐1R) dual agonist with the potential to induce greater weight reductions than GLP‐1R mono‐agonists. We report the design and baseline participant characteristics of the SYNCHRONIZE‐JP trial evaluating survodutide in Japanese adults with obesity disease ( ClinicalTrials.gov : NCT06176365).

Materials and Methods:

SYNCHRONIZE‐JP is a 76‐week, randomised, double‐blind, parallel‐group, multi‐centre, phase 3 clinical trial. Eligible participants were aged ≥ 18 years, with BMI ≥ 35 kg/m 2 with ≥ 1 obesity complication or BMI ≥ 27 kg/m 2 with ≥ 2 obesity complications, ≥ 1 self‐reported unsuccessful dietary effort to lose body weight and ≥ 1 obesity complication required to be type 2 diabetes (T2D; capped at 30% enrolment), hypertension or dyslipidaemia. Participants were randomised 1:1:1 to receive once‐weekly survodutide 3.6 or 6.0 mg, or placebo, accompanied by a reduced‐calorie diet and increased physical activity. The primary endpoints are percentage change in body weight and achievement of body weight reduction ≥ 5% from baseline to Week 76. A subset of participants will be assessed for additional endpoints of liver fat content and body composition.

Results:

Of 274 enrolled participants, 24.1% had T2D. The mean age was 53.1 years; 47.8% were female, and mean BMI was 33.2 kg/m 2 . The most frequent complications were dyslipidaemia (81.4%), hypertension (72.6%), hyperuricaemia (30.3%) and metabolic dysfunction‐associated steatotic liver disease (26.6%).

Conclusions:

The results of SYNCHRONIZE‐JP will provide Japan‐specific efficacy, safety and tolerability data for survodutide and inform its potential role in the management of obesity disease.

2026-05-01·JACC-Heart Failure

Survodutide for the Treatment of Obesity

Article

作者: Platz, Elke ; Hussain, Samina Ajaz ; Wharton, Sean ; Burger, Svenja ; Kosiborod, Mikhail N ; Startseva, Elena ; Fey, Constanze ; Brueckmann, Martina ; le Roux, Carel W ; Kaplan, Lee M ; Bozkurt, Biykem

2026-05-01·Lancet Diabetes & Endocrinology

Beyond weight loss: multisystem benefits of obesity medications

Review

作者: van Rossum, Elisabeth F C ; Savas, Mesut ; Kuckuck, Susanne ; Boon, Mariëtte R

Obesity is increasingly managed with medications as disease-modifying therapies, reflecting its role as a gateway disease driving metabolic, cardiovascular, reproductive, neuropsychiatric, and mechanical conditions. This Review synthesises evidence from randomised controlled trials and high-quality meta-analyses on approved and late-stage investigational obesity medications, including phentermine-topiramate, naltrexone-bupropion, glucagon-like peptide-1 (GLP-1) receptor agonists (eg, liraglutide, semaglutide, subcutaneously and orally), and newer GLP-1 receptor agonist-based agents (eg, tirzepatide, survodutide, mazdutide, retatrutide, cagrilintide-semaglutide, and amycretin). We evaluated the effects of obesity medications across major obesity-related conditions, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, heart failure, cardiovascular disease, obstructive sleep apnoea syndrome, polycystic ovary syndrome (recently named polyendocrine metabolic ovarian syndrome), osteoarthritis, muscle mass, depression, quality of life, and food cravings, along with binge-eating disorders, substance use disorders, and neurodegenerative diseases. Overall, GLP-1-based and multiagonist therapies show beneficial effects across these comorbid conditions. While many benefits of obesity medications are mediated by weight loss, accumulating evidence indicates important weight loss-independent effects, particularly with GLP-1 receptor agonist-based therapies. A broader understanding of these pleiotropic effects is essential to inform personalised obesity management and optimise long-term clinical outcomes.

483

项与索弗度肽相关的新闻（医药）

2026-08-20

·北京医学感染与传染研究

自然医学 32卷 7-8期（2026年8月20日更新）

Nature Medicine Volume 32 Issue 7 自然医学 32卷 7期 https://www.nature.com/nm/volumes/32/issues/7 Editorial（社论） 1 Oncology must confront hidden side effects 肿瘤学必须正视隐匿不良反应 Nature Medicine volume 32（7）, page 2321 News（新闻） 2 Taming the inflamed heart 调控炎症性心脏病变 Charlotte Harrison Nature Medicine volume 32（7）, pages 2322-2323 News Feature（新闻专题） 3 When the real world becomes the trial 当现实世界成为临床试验场域 Marianne Guenot Nature Medicine volume 32（7）, pages 2324–2327 Correspondence（读者来信） 4 What Galen’s dissections reveal about tacit learning in modern medical education 盖伦解剖研究对现代医学教育中默会学习的启示 Andres PelavskiGabriele TorcolettiOrly Lewis Nature Medicine volume 32（7）, pages 2328–2329 5 What Utah’s clinical AI sandbox reveals about independent oversight 犹他州临床人工智能沙箱对独立监管机制的启示 Rahul GorijavoluNikhil JaiswalLeo Anthony Celi Nature Medicine volume 32（7）, pages 2330–2332 6 A case of artificial intelligence-enhanced diagnostics leading to heart transplantation 人工智能辅助诊断促成心脏移植一例 Heidi S. HartmanJoshua FinerPierre Elias Nature Medicine volume 32（7）, pages 2333–2334 7 Unintended consequences of legacy oversight in digital medicine 数字医学领域传统监管模式带来的非预期后果 Jochen K. LennerzDaniela AllendeAnne M. Stowman Nature Medicine volume 32（7）, pages 2335–2337 8 Incretin therapies, nutrition and food insecurity in the UK 英国肠促胰素治疗、营养状况与粮食不安全问题 Marie SpreckleyCara F. RuggieroAdrian Brown Nature Medicine volume 32（7）, pages 2338–2339 World View（全球观点） 9 Manageable toxicity is not a label — it is an oxymoron 可控制毒性并非标签，而是矛盾表述 From the patient’s perspective, toxicity is manageable only when it is met with empathy. 从患者视角而言，只有饱含人文关怀，不良反应才谈得上可控。 Laura Book Nature Medicine volume 32（7）, page 2340 10 Downplaying toxicities in cancer drug trials is not acceptable 肿瘤药物临床试验中淡化不良反应不可取 Bishal Gyawali Nature Medicine volume 32（7）, page 2341 Comment（述评） 11 Wearables as personal health custodians 可穿戴设备：个人健康守护者 Lei LuJosip Car Nature Medicine volume 32（7）, pages 2342–2345 12 Australia legislates against genetic discrimination in life insurance 澳大利亚立法禁止人寿保险领域的基因歧视 Jane Tiller Nature Medicine volume 32（7）, pages 2346–2348 13 A roadmap to competitive preclinical packages 具备竞争力的临床前研究方案构建路线图 Mustafa KhasrawMegan C. BenzJose R. Conejo-Garcia Nature Medicine volume 32（7）, pages 2349–2352 14 Brain Health for Economic Resilience: a data-driven framework for the brain-positive economic transition 保障大脑健康助力经济韧性：推动益脑经济转型的数据驱动框架 Harris A. EyreRym AyadiSimon Fischer-Baum Nature Medicine volume 32（7）, pages 2353–2355 News & Views（新闻与观点） 15 Long-term health risks of e-cigarettes after smoking cessation 戒烟后使用电子烟的长期健康风险 Mahdi SheikhPamela M. Ling Nature Medicine volume 32（7）, pages 2356–2357 16 CAR T cells take on precancers CAR-T细胞靶向癌前病变 Eric M. JurgensSham Mailankody Nature Medicine volume 32（7）, pages 2358–2359 17 Lassa fever countermeasures gather pace 拉沙热防控举措加速推进 Daniel Jenkin Nature Medicine volume 32（7）, pages 2360–2361 18 Shifting the goalposts in obesity drug development 肥胖药物研发目标的重新界定 W. Timothy Garvey Nature Medicine volume 32（7）, pages pages 2362–2363 Research Briefings（研究简报） 19 General-purpose chatbots outperform clinical AI tools on physicians’ real-world questions 通用对话机器人在医师现实临床问题上表现优于专用临床人工智能工具 Nature Medicine volume 32（7）, pages 2364–2365 20 An AI framework for multi-disease detection via retinal imaging 基于视网膜影像的多疾病筛查人工智能框架 Nature Medicine volume 32（7）, pages 2366–2367 Perspectives（前瞻观点） 21 Immune aging biomarkers for clinical trials 适用于临床试验的免疫衰老生物标志物 Andrea CiprianoJamie JusticeChiara M. S. Herzog Nature Medicine volume 32（7）, pages 2368–2382 Review Articles（综述） 22 Biological aging clocks in health and disease 健康与疾病状态下的生物学衰老时钟 Tony Wyss-CorayEric J. Topol Nature Medicine volume 32（7）, pages 2383–2394 Matters Arising（学术争鸣） 23 Limited evidence of AI superiority in seasonal influenza vaccine strain selection 尚无充分证据证明人工智能在季节性流感疫苗毒株筛选中具备优势 Simon P. J. de JongColin A. Russell Nature Medicine volume 32（7）, pages 2395–2397 24 Reply to: Limited evidence of AI superiority in seasonal influenza vaccine strain selection 对《尚无充分证据证明人工智能在季节性流感疫苗毒株筛选中具备优势》一文的回应 Wenxian ShiJeremy WohlwendRegina Barzilay Nature Medicine volume 32（7）, pages 2398–2400 Brief Communications（简讯） 25 Spatiotemporal diffusion of the 2024 Oropouche outbreak in Cuba 2024年古巴奥罗普切热暴发的时空传播特征 Rosario GravierMelissa M. PerezMaria G. Guzman Nature Medicine volume 32（7）, pages 2401–2404 26 General-purpose large language models outperform specialized clinical AI tools on medical benchmarks 通用大语言模型在医学基准测试中优于专用临床人工智能工具 Krithik VishwanathAnton AlyakinEric Karl Oermann Nature Medicine volume 32（7）, pages 2405–2409 Articles（论著） 27 Electronic cigarette use after smoking cessation and lung cancer risk 戒烟后使用电子烟与肺癌风险 Yeon Wook KimEung Joo ParkChoon-Taek Lee Nature Medicine volume 32（7）, pages 2410–2419 28 Ciltacabtagene autoleucel in high-risk smoldering multiple myeloma: the CAR-PRISM phase 2 trial Ciltacabtagene autoleucel治疗高危冒烟型（无症状）多发性骨髓瘤：CAR-PRISMⅡ期临床试验 Omar NadeemDavid M. Cordas dos SantosIrene M. Ghobrial Nature Medicine volume 32（7）, pages 2420–2429 29 Cibisatamab and FAP-4-1BBL in microsatellite-stable colorectal cancer: a phase 1b trial Cibisatamab联合FAP-4-1BBL治疗微卫星稳定型结直肠癌：Ⅰb期临床试验 Ignacio MeleroTamara TanosVictor Moreno Nature Medicine volume 32（7）, pages 2430–2439 30 Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial 基于Teclistamab的诱导方案治疗适合移植初诊多发性骨髓瘤：Ⅱ期临床试验 Marc S. RaabNiels WeinholdK. Martin Kortüm Nature Medicine volume 32（7）, pages 2440–2448 31 Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial 抗LAG-3单抗联合或不联合抗PD-1单抗治疗复发性胶质母细胞瘤：Ⅰ期临床试验 Michael LimXiaobu YeStuart A. Grossman Nature Medicine volume 32（7）, pages 2449–2460 32 Neoadjuvant stereotactic body radiation therapy with durvalumab and oleclumab in ER+HER2− breast cancer: a randomized phase 2 trial 立体定向体部放疗联合度伐利尤单抗与奥来鲁单抗新辅助治疗ER阳性HER2阴性乳腺癌：随机Ⅱ期临床试验 Alex De CaluwéIsabelle DesmoulinsLaurence Buisseret Nature Medicine volume 32（7）, pages 2461–2472 33 Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial ctDNA阳性结直肠癌术后辅助化疗：随机Ⅲ期临床试验 Hideaki BandoJun WatanabeTakeshi Kato Nature Medicine volume 32（7）, pages 2473–2480 34 Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial 多抗原靶向T细胞治疗儿童中枢神经系统肿瘤：Ⅰ期临床试验 Stephanie GomezRachel A. DiCioccioEugene I. Hwang Nature Medicine volume 32（7）, pages 2481–2493 35 AI framework for multidisease detection via retinal imaging 基于视网膜影像的多疾病筛查人工智能框架 Xiayin ZhangQinyi LiHonghua Yu Nature Medicine volume 32（7）, pages 2494–2503 36 Long-term independent use of an intracortical brain–computer interface for speech and cursor control 皮层内脑机接口用于语音与光标控制的长期独立应用研究 Nicholas S. CardTyler Singer-ClarkDavid M. Brandman Nature Medicine volume 32（7）, pages 2504–2510 37 Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial 含佐剂灭活狂犬病毒载体拉沙病毒疫苗在健康成人中的Ⅰ期临床试验 Justin R. OrtizDrishya KurupMatthias J. Schnell Nature Medicine volume 32（7）, pages 2511–2521 38 Favipiravir for Lassa fever: an open-label, randomized controlled phase 2 trial 法匹拉韦治疗拉沙热：开放标签随机对照Ⅱ期临床试验 Cyril EramehKevin OkwaraekeMirjam Groger Nature Medicine volume 32（7）, pages 2522–2532 39 Bispecific 10E8.4/iMab broadly neutralizing antibody in people with or without HIV-1: a partially randomized phase 1 trial 双特异性广谱中和抗体10E8.4/iMab在HIV-1感染者与健康人群中的部分随机Ⅰ期临床试验 Deborah A. TheodoreBryan T. MayerMagdalena E. Sobieszczyk Nature Medicine volume 32（7）, pages 2533–2545 40 15-strain live biotherapeutic product or same donor fecal microbiota transplant for recurrent Clostridioides difficile infection: a randomized phase 1b trial 15菌株活体生物制剂与同源供体粪菌移植治疗复发性艰难梭菌感染：随机Ⅰb期临床试验 Lukas BethlehemLorenza BartuAri Grinspan Nature Medicine volume 32（7）, pages 2546–2555 41 Innate immune responsiveness predicts enhanced cellular immunity and symptomatic disease after controlled human influenza infection 固有免疫应答水平可预测人工流感感染后细胞免疫增强与临床发病情况 Loukas PapargyrisJiayun XuChristopher Chiu Nature Medicine volume 32（7）, pages 2556–2569 42 Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial 多巴胺激动剂普拉克索治疗快感缺失型抑郁症的疗效与靶点作用验证：随机安慰剂对照试验 Filip VentorpMarie AspDaniel Lindqvist Nature Medicine volume 32（7）, pages 2570–2578 43 Spinal cord stimulation for upper limb motor function in people with chronic post-stroke hemiparesis: a feasibility trial 脊髓电刺激改善慢性卒中后偏瘫患者上肢运动功能：可行性临床试验 Roberto M. de FreitasShovan BhatiaMarco Capogrosso Nature Medicine volume 32（7）, pages 2579–2590 44 A neuroprosthesis for restoring hand movement and sensation in a person with complete tetraplegia 神经假体用于重建完全四肢瘫痪患者手部运动与感觉功能 Santosh ChandrasekaranSarah K. WandeltChad E. Bouton Nature Medicine volume 32（7）, pages pages2591–2601 45 Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial 双靶点基因疗法治疗帕金森病：多中心Ⅰ期临床试验 Mengyue NiuJifeng GuoJun Liu Nature Medicine volume 32（7）, pages 2602–2609 46 Abatacept versus hydroxychloroquine for prevention of rheumatoid arthritis in individuals with palindromic rheumatism: a randomized open-label trial 阿巴西普对比羟氯喹预防复发性风湿症进展为类风湿关节炎：随机开放标签试验 Raimon SanmartiCarolina Pérez-GarcíaIsabel Haro Nature Medicine volume 32（7）, pages 2610–2618 47 Oligonucleotide–siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial 寡核苷酸-siRNA偶联药物治疗SOD1相关肌萎缩侧索硬化：Ⅰ期临床试验 Weiqi ChenLingling JiangYilong Wang Nature Medicine volume 32（7）, pages 2619–2628 48 Multinational validation of the PREVENT and SCORE2心血管风险方程 across 6.4 million individuals 基于640万人群的多国验证：PREVENT与SCORE2心血管风险预测方程 Brendon L. NeuenRupert W. MajorVilmantas Giedraitis Nature Medicine volume 32（7）, pages 2629–2638 49 Cliramitug for depletion of cardiac amyloid transthyretin: long-term follow-up of the NI006-101 trial Cliramitug清除心脏转甲状腺素蛋白淀粉样物质：NI006-101试验长期随访结果 Peter C. KahrFabian aus dem SiepenPeter van der Meer Nature Medicine volume 32（7）, pages 2639–2646 50 Low-dose digoxin in patients with heart failure with reduced or mildly reduced ejection fraction: a randomized controlled trial 小剂量地高辛治疗射血分数降低或轻度降低心力衰竭：随机对照试验 D. J. van VeldhuisenM. RienstraP. van der Meer Nature Medicine volume 32（7）, pages 2647–2653 51 The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial 微小RNA抑制剂CDR132L治疗心肌梗死后左室射血分数降低患者：随机Ⅱ期临床试验 Johann BauersachsScott D. SolomonThomas Thum Nature Medicine volume 32（7）, pages 2654–2661 52 Semaglutide versus placebo in individuals with poor weight loss after bariatric surgery: a double-blinded, randomized, placebo-controlled trial 司美格鲁肽对比安慰剂治疗减重手术术后减重不佳人群：双盲随机安慰剂对照试验 Chloe StanleyRitwika MallikJanine Makaronidis Nature Medicine volume 32（7）, pages 2662–2672 53 Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial Apitegromab用于替尔泊肽减重过程中维持瘦体重：随机双盲安慰剂对照Ⅱ期临床试验 Richard E. PratleyDouglas Scott DenhamJing L. Marantz Nature Medicine volume 32（7）, pages 2673–2678 54 Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial Orforglipron用于维持减重效果：双盲随机Ⅲb期ATTAIN-MAINTAIN试验 Louis J. AronneDeborah B. HornNeena Xavier Nature Medicine volume 32（7）, pages 2679–2687 Amendments & Corrections（勘误与更正） 55 Author Correction: Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial 作者更正：基于Teclistamab的诱导方案治疗适合移植初诊多发性骨髓瘤：Ⅱ期临床试验 Marc S. RaabNiels WeinholdK. Martin Kortüm Nature Medicine volume 32（7）, page 2688 56 Author Correction: Digital AVATAR therapy for distressing voices in psychosis: the phase 2/3 AVATAR2 trial 作者更正：数字虚拟化身疗法治疗精神病幻听症状：Ⅱ/Ⅲ期AVATAR2临床试验 Philippa A. GaretyClementine J. EdwardsThomas Ward Nature Medicine volume 32（7）, page 2689 57 Author Correction: Global burden of amphetamine, cannabis, cocaine and opioid use in 204 countries, 1990–2023: a Global Burden of Disease Study 作者更正：1990–2023年204个国家苯丙胺、大麻、可卡因与阿片类物质使用的全球疾病负担研究 Jiseung KangHyeon Jin KimDong Keon Yon Nature Medicine volume 32（7）, page 2690 58 Retraction Note: Time-of-day immunochemotherapy in non-small cell lung cancer: a randomized phase 3 trial 撤稿声明：时辰免疫化疗治疗非小细胞肺癌：随机Ⅲ期临床试验 Zhe HuangLiang ZengYongchang Zhang Nature Medicine volume 32（7）, page 2691 Nature Medicine Volume 32 Issue 8 自然医学 32卷 8期 https://www.nature.com/nm/volumes/32/issues/8 Editorial（社论） 1 Anti‑aging interventions need less hype and more clinical evidence 抗衰老干预：少一些炒作，多一些临床证据 Editorial Nature Medicine volume 32（8）, page 2693 News（新闻） 2 A turning point for gene editing in severe blood disorders 基因编辑治疗重症血液疾病迎来转折点 Carrie Arnold Nature Medicine volume 32（8）, pages 2694-2696 News Feature（新闻特写） 3 Sleep as therapy 睡眠疗法 Carrie Arnold Nature Medicine volume 32（8）, pages 2697–2700 Correspondence（通信） 4 Genetic–exposome interactions and aging clocks in dementia: the ReDLat2 initiative 遗传‑暴露组相互作用与痴呆衰老时钟：ReDLat2研究计划 Agustin IbáñezJennifer S. YokoyamaBruce L. Miller Nature Medicine volume 32（8）, pages 2701–2703 5 Bundibugyo Ebola without vaccines or therapeutics: why public health fundamentals matter more than border closures 无疫苗与治疗药物情况下的本迪布焦埃博拉疫情：公共卫生基础措施比边境封锁更为重要 Ngashi NgongoMosoka Papa FallahJean Kaseya Nature Medicine volume 32（8）, pages 2704–2705 6 Fertilizer scarcity as a failure of global health governance 肥料短缺：全球卫生治理的一项失败 Alaha NasariAmina NasariJessica Fanzo Nature Medicine volume 32（8）, pages 2706–2707 7 Mapping the human chemical exposome for public health 面向公共卫生的人类化学暴露组图谱绘制 Arthur DavidSarah LennonMichel Samson Nature Medicine volume 32（8）, pages 2708–2710 World View（全球视野） 8 When caution becomes harm 当谨慎变为伤害 Simone N. Vigod Nature Medicine volume 32（8）, page 2711 Comment（述评） 9 Enabling secure discovery in trusted research environments with improved tooling 依托优化工具在可信研究环境中实现安全数据挖掘 Vincent J. StraubMelinda C. Mills Nature Medicine volume 32（8）, pages 2712–2715 10 Reinventing biotech systems for patient impact 重塑生物技术体系，惠及患者 Kushal T. KadakiaYashodhara DashAnaeze C. Offodile II Nature Medicine volume 32（8）, pages 2716–2719 11 Why large‑scale randomized trials of live‑attenuated shingles vaccination for dementia prevention are urgently needed 亟需开展减毒活带状疱疹疫苗预防痴呆的大规模随机对照试验 Pascal Geldsetzer Nature Medicine volume 32（8）, pages 2720–2723 12 Inspiring, shaping and sustaining an African research & development agenda 推动、构建并维系非洲研发议程 Mosoka P. FallahMisaki WayengeraJean Kaseya Nature Medicine volume 32（8）, pages 2724–2726 13 Data rights are the missing pillar for modernizing consent in medicine 数据权利：医学知情同意现代化的缺失支柱 Nada S. Salem Nature Medicine volume 32（8）, pages 2727–2728 Q&A（问答） 14 Reinventing health communication for the digital era 数字时代下重塑健康传播 Natalie Healey Collection: Nature Medicine Commission on Quality Health Information for All Nature Medicine volume 32（8）, pages 2729–2731 News & Views（新闻与观点） 15 Adaptive brain stimulation 2.0 for Parkinsonian gait 用于帕金森病步态障碍的第二代自适应脑刺激 Arjun BalachandarAlfonso Fasano Nature Medicine volume 32（8）, pages 2732–2734 16 A second chance for gene therapy to restore natural hearing 基因治疗重获契机，助力恢复天然听力 Nicola Strenzke Nature Medicine volume 32（8）, pages 2735–2737 17 From RAS inhibitor resistance to rational combination strategies 从RAS抑制剂耐药到合理联合治疗策略 Paula LynchTeresa MacarullaGrainne M. O’Kane Collection: Cancer at Nature Portfolio Nature Medicine volume 32（8）, pages 2738–2740 18 Deciphering the role of histidine in cancer 解析组氨酸在肿瘤中的作用 Feyza CansizAmanda N. PopeAlpaslan Tasdogan Nature Medicine volume 32（8）, pages 2741–2742 Research Briefings（研究简报） 19 Learning from routine health system data builds better neuroimaging AI models 基于常规卫生系统数据训练构建更优神经影像人工智能模型 Research Briefing Nature Medicine volume 32（8）, pages 2743–2744 20 Early detection of Alzheimer’s disease with circular RNA from blood 基于血液环状RNA实现阿尔茨海默病早期检测 Nature Medicine volume 32（8）, pages 2745–2746 21 Non‑invasive tests for the evaluation of liver fibrosis in MASLD 代谢相关脂肪性肝病肝纤维化的无创评估检测 Nature Medicine volume 32（8）, pages 2747–2748 22 Multi‑omics maps human–pig interactions in extracorporeal liver cross‑circulation 多组学解析体外肝交叉循环中人‑猪相互作用 Nature Medicine volume 32（8）, pages 2749–2750 23 Biological aging might help to explain the rising risk of early‑onset cancer 生物衰老或可解释早发性肿瘤风险升高现象 Nature Medicine volume 32（8）, pages 2751–2752 24 Delivering the benefits of genomic data reanalysis for diagnosis equitably and at scale 公平、规模化发挥基因组数据再分析的诊断价值 Nature Medicine volume 32（8）, pages 2753–2754 25 Why high scores do not mean application readiness for health AI 为何高分不等于健康人工智能具备实际应用就绪度 Nature Medicine volume 32（8）, pages 2755–2756 Perspectives（观点） 26 Type 2 diabetes prevention across the life course 全生命周期的2型糖尿病预防 Yiying WangJennifer L. SargentAndreas L. Birkenfeld Nature Medicine volume 32（8）, pages 2757–2773 27 The next generation of antibody–drug conjugates 新一代抗体‑药物偶联物 F. MoseleA. PeltierF. André Collection: Cancer at Nature Portfolio Nature Medicine volume 32（8）, pages 2774–2785 Brief Communications（简讯） 28 Clinical profile and genomic characterization of the 2026 Bundibugyo virus index case in Uganda 乌干达2026年本迪布焦病毒首发病例的临床特征与基因组分析 Andrew NsawotebbaIsaac SsewanyanaDiana Atwine Nature Medicine volume 32（8）, pages 2786–2789 Articles（论著） 29 Immersive virtual reality with synchronous neurostimulation for upper‑limb recovery after stroke: a randomized feasibility trial 沉浸式虚拟现实联合同步神经刺激用于脑卒中后上肢功能恢复：一项随机可行性试验 Giuseppe Valerio AurucciOlivera DjordjevicStanisa Raspopovic Nature Medicine volume 32（8）, pages 2790–2802 30 Adaptive deep brain stimulation for dynamic gait control in Parkinson’s disease: a randomized feasibility trial 自适应深部脑刺激用于帕金森病动态步态调控：一项随机可行性试验 Kenneth H. LouieJannine P. BalakidDoris D. Wang Nature Medicine volume 32（8）, pages 2803–2814 31 Activity‑dependent adaptive deep brain stimulation improves gait in Parkinson’s disease 活动依赖性自适应深部脑刺激改善帕金森病患者步态 Stefano ScafaValeria de SetaEduardo M. Moraud Nature Medicine volume 32（8）, pages 2815–2830 32 Health system learning enables generalist neuroimaging models 基于卫生系统数据学习构建通用型神经影像模型 Akhil KondepudiAkshay RaoTodd Hollon Nature Medicine volume 32（8）, pages 2831–2837 33 Individualized antisense oligonucleotides for SCN2A‑related developmental epileptic encephalopathy 针对SCN2A相关发育性癫痫性脑病的个体化反义寡核苷酸治疗 Olivia Kim‑McManusLaurence MignonElizabeth Berry‑Kravis Nature Medicine volume 32（8）, pages 2838–2845 34 Re‑administration of AAV‑mediated gene therapy for OTOF‑related deafness: a single‑arm trial OTOF相关耳聋腺相关病毒介导基因治疗的再次给药：一项单臂临床试验 Xintai FanLonglong ZhangYilai Shu Nature Medicine volume 32（8）, pages 2846–2856 35 Blood‑based circular RNAs for early diagnosis of Alzheimer’s disease 基于血液环状RNA的阿尔茨海默病早期诊断 Bridget PhillipsJessie SanfordCarlos Cruchaga Nature Medicine volume 32（8）, pages 2857–2864 36 Acquired resistance to the RAS(ON) multi‑selective inhibitor daraxonrasib guides rational combination therapy strategies in pancreatic cancer RAS(ON)高选择性抑制剂daraxonrasib获得性耐药指导胰腺癌合理联合治疗策略 Ida AronchikSumit KarMallika Singh Collection: Cancer at Nature Portfolio Nature Medicine volume 32（8）, pages 2865–2877 37 MAGE‑A4/MAGE‑A8‑targeted TCR‑based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial 靶向MAGE‑A4/MAGE‑A8的TCR双特异性T细胞衔接分子治疗复发/难治性实体瘤：Ⅰ期临床试验 Martin WermkeSebastian OchsenreitherCarsten Reinhardt Nature Medicine volume 32（8）, pages 2878–2887 38 Savolitinib in MET‑amplified gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial 赛沃替尼治疗MET扩增胃癌或胃食管结合部腺癌：Ⅱ期临床试验 Zhi PengTianshu LiuZhongxian Zheng Nature Medicine volume 32（8）, pages 2888–2897 39 SEZ6‑targeting antibody−drug conjugate ABBV‑706 in advanced small cell lung cancer and solid tumors: a phase 1 trial 靶向SEZ6抗体‑药物偶联物ABBV‑706治疗晚期小细胞肺癌及其他实体瘤：Ⅰ期临床试验 Lauren Averett ByersByoung Chul ChoSreenivasa Chandana Nature Medicine volume 32（8）, pages 2898–2908 40 FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial FcRH5×CD3双特异性抗体ce vostamab治疗复发难治多发性骨髓瘤：Ⅰ期临床试验 Adam D. CohenJoshua RichterAmrita Krishnan Nature Medicine volume 32（8）, pages 2909–2917 41 Metabolic determinants of cancer immunotherapy outcomes identified by plasma profiling 基于血浆谱分析筛选肿瘤免疫治疗疗效的代谢决定因素 Déborah SuissaMarine FidelleLaurence Zitvogel Nature Medicine volume 32（8）, pages 2918–2932 42 Polypill for heart failure with reduced ejection fraction: the POLY‑HF randomized trial 射血分数降低心力衰竭复方制剂：POLY‑HF随机临床试验 Ambarish PandeyNeil KeshvaniThomas J. Wang Nature Medicine volume 32（8）, pages 2933–2940 43 Oral small molecule GLP‑1 receptor agonist aleniglipron in people with overweight or obesity: a randomized, double‑blind, placebo‑controlled phase 2b trial 口服小分子GLP‑1受体激动剂aleniglipron治疗超重/肥胖人群：随机双盲安慰剂对照Ⅱb期临床试验 Julio RosenstockIldiko LingvayBlai Coll Nature Medicine volume 32（8）, pages 2941–2947 44 Survodutide in adults with obesity and metabolic dysfunction‑associated steatotic liver disease: SYNCHRONIZE‑MASLD, a randomized, double‑blind, placebo‑controlled phase 3 trial Survodutide治疗合并代谢相关脂肪性肝病的肥胖成人：SYNCHRONIZE‑MASLD随机双盲安慰剂对照Ⅲ期临床试验 Lee M. KaplanElena StartsevaPaul Hellstern Nature Medicine volume 32（8）, pages 2948–2958 45 Prospective validation of imaging and serum diagnostic biomarkers of steatohepatitis and fibrosis in MASLD: the LITMUS Imaging Study 代谢相关脂肪性肝炎及肝纤维化影像与血清诊断生物标志物的前瞻性验证：LITMUS影像研究 Michael PavlidesYasaman ValiQuentin M. Anstee Nature Medicine volume 32（8）, pages 2959–2969 46 Longitudinal multiomics profiling of extracorporeal cross‑circulation with pig liver xenografts in human decedents 人逝者猪肝异种移植体外交叉循环的纵向多组学分析 Qian GuoChan WangBrendan J. Keating Nature Medicine volume 32（8）, pages 2970–2982 47 Biological aging and generational shifts in early‑onset cancer risk 生物衰老与早发性肿瘤风险的代际变迁 Ruiyi TianXiaoyu ZongYin Cao Nature Medicine volume 32（8）, pages 2983–2990 48 Automated reanalysis of genomic data for rare disease diagnostics at scale 面向大规模罕见病诊断的基因组数据自动化再分析 Matthew J. WellandK. D. AhlquistZornitza Stark Nature Medicine volume 32（8）, pages 2991–2999 49 Divergent impacts of explainable AI for dermatological diagnosis on clinicians versus lay people 可解释人工智能皮肤病诊断对临床医师与普通人群的差异化影响 Xuhai ‘Orson’ XuHaoyu HuMarzyeh Ghassemi Nature Medicine volume 32（8）, pages 3000–3009 50 Generalizable AI predicts immunotherapy outcomes across cancers and treatments 泛化人工智能跨肿瘤类型与治疗方案预测免疫治疗疗效 Wanxiang ShenIntae MoonMarinka Zitnik Nature Medicine volume 32（8）, pages 3010–3022 51 Evaluating the robustness and readiness of large frontier models in health AI applications 健康人工智能应用中大前沿模型的稳健性与就绪度评估 Yu GuJingjing FuPaul Vozila Nature Medicine volume 32（8）, pages 3023–3031 52 Generative AI‑enabled clinical decision support system in primary care: a pragmatic, cluster‑randomized trial 基层医疗机构生成式人工智能临床决策支持系统：一项实用整群随机试验 Ambrose AgweyuPaul MwanikiBilal A. Mateen Nature Medicine volume 32（8）, pages 3032–3039 53 Integrated care pathway in individuals with Long COVID: STIMULATE‑ICP, a cluster‑randomized, phase 3 trial 长新冠患者综合护理路径：STIMULATE‑ICP整群随机Ⅲ期临床试验 Amitava BanerjeeGordon PrescottYi Mu Nature Medicine volume 32（8）, pages 3040–3047 54 Maternal 6‑valent group B Streptococcus vaccine in non‑pregnant and pregnant females: a randomized phase 1/2 trial B族链球菌六价母体疫苗在非妊娠及妊娠女性中的随机Ⅰ/Ⅱ期临床试验 Shabir A. MadhiHasra SnaggsAlejandra Gurtman Nature Medicine volume 32（8）, pages 3048–3059 55 The genetic architecture of fibromyalgia across 2.5 million individuals 基于250万人群的纤维肌痛遗传结构研究 Isabel KerrebijnGyda BjornsdottirMichael Wainberg Nature Medicine volume 32（8）, pages 3060–3070 56 Povorcitinib for hidradenitis suppurativa: the randomized, double‑blind, placebo‑controlled STOP‑HS1 and STOP‑HS2 phase 3 trials Povorcitinib治疗化脓性汗腺炎：随机双盲安慰剂对照STOP‑HS1、STOP‑HS2两项Ⅲ期临床试验 Martina L. PorterAntonio MartorellChristos C. Zouboulis Nature Medicine volume 32（8）, pages 3071–3081 Analysis（分析） 57 A meta‑analysis of the long‑term effects of antihypertensive therapy on the risk of major cardiovascular disease across 51 randomized trials 纳入51项随机试验的降压治疗对主要心血管病风险长期影响的荟萃分析 Qianqian YangZeinab BidelKazem Rahimi Nature Medicine volume 32（8）, pages 3082–3092 Amendments & Corrections（修订与勘误） 58 Author Correction: SEZ6‑targeting antibody−drug conjugate ABBV‑706 in advanced small cell lung cancer and solid tumors: a phase 1 trial 作者勘误：靶向SEZ6抗体‑药物偶联物ABBV‑706治疗晚期小细胞肺癌及其他实体瘤：Ⅰ期临床试验 Lauren Averett ByersByoung Chul ChoSreenivasa Chandana Nature Medicine volume 32（8）, page 3093 59 Author Correction: MAGE‑A4/MAGE‑A8‑targeted TCR‑based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial 作者勘误：靶向MAGE‑A4/MAGE‑A8的TCR双特异性T细胞衔接分子治疗复发/难治性实体瘤：Ⅰ期临床试验 Martin WermkeSebastian OchsenreitherCarsten Reinhardt Nature Medicine volume 32（8）, page 3094 60 Publisher Correction: Oral small molecule GLP‑1 receptor agonist aleniglipron in people with overweight or obesity: a randomized, double‑blind, placebo‑controlled phase 2b trial 出版方勘误：口服小分子GLP‑1受体激动剂aleniglipron治疗超重/肥胖人群：随机双盲安慰剂对照Ⅱb期临床试验 Julio RosenstockIldiko LingvayBlai Coll Nature Medicine volume 32（8）, page 3095

临床研究细胞疗法免疫疗法基因疗法

2026-08-19

·南模生物SMOC

GLP1R新时代，动物模型如何精准赋能？

GLP-1受体激动剂（GLP-1RA）是过去二十年代谢疾病领域最具革命性的药物类别之一。从2005年首款产品艾塞那肽获批至今，GLP-1R相关研发管线已近800条。在如此程度的竞争下，GLP-1R相关代谢药物的研发思路已从“单靶点长效化”进入几个新阶段：口服便携化——旨在提高依从性、降低成本、避免注射多靶点协同——旨在追求更强减重与代谢获益适应症拓展——旨在突破糖尿病/肥胖标签，竞争其他赛道在上述新方向的研发中，动物模型的要求也在不断提高。从单一靶点到多靶点人源化代谢疾病模型，从传统药效终点到多组学动态监测，如何构建与新一代GLP-1R药物研发需求相匹配的精准动物模型，已成为赛道突围中不可回避的核心技术命题。口服药物研发需更精准动物模型支撑口服便携化是GLP-1R药物研发中技术门槛较高的方向之一。与注射剂不同，口服GLP-1RA面临多肽药物的胃肠道降解、黏膜屏障穿透力低、生物利用度差等多重挑战。目前，口服GLP-1药物的研发主要以两种方式进行：口服多肽制剂和口服小分子非肽类制剂。口服多肽制剂方面，目前诺和诺德的司美格鲁肽口服片已全球获批上市，它通过了吸收增强剂SNAC技术，在胃内局部升高pH值、保护司美格鲁肽不被胃蛋白酶降解，同时促进药物跨胃黏膜上皮细胞吸收。口服小分子非肽类制剂方面，研发思路是利用小分子GLP-1RA的分子量远小于多肽的优势，设计为高生物利用度的口服制剂。然而，小分子激动剂往往对人GLP-1R具有高度种属选择性，在野生型啮齿动物中可能完全不激活受体。这一特写对动物模型均提出了更为严苛的要求。南模生物的hGLP1R人源化小鼠可有效支撑小分子口服GLP-1RA的体内活性验证与药效评价，是口服便携化方向研发不可或缺的核心工具。 hGLP1R小鼠（NM-HU-200220）验证数据 Fig. 1 The efficacy of orforglipron in hGLP1R mice. The hGLP1R mice were fed CD or HFD. Administer saline or oroglipron orally once daily until euthanasia. Semaglutide was administered subcutaneously once daily until euthanasia. 多靶点协同思路中动物模型的关键支撑多靶点GLP-1药物已成为代谢疾病治疗领域的核心发展方向，目前与 GLP-1R 协同开发的“多靶点”策略，集中在几条生理轴：肠促胰素轴：GIPR、GCGR等食欲/饱腹感轴：Amylin、PYY/NPY2、GDF15/GFRAL、MC4R等代谢/肝脏轴：FGF21等体成分/肌肉轴：Activin/Myostatin 通路图. 在临床前研究中新一代GLP-1R相关靶点的主要作用。[1] 从靶点组合来看，目前较为热门的有以下几种组合： GLP-1R / GIPR GLP-1R/GIPR双靶点激动剂是目前多靶点策略中临床验证最为充分的方向。GIPR是葡萄糖依赖性促胰岛素多肽受体，其配体GIP由肠道K细胞分泌，主要作用是促胰岛素分泌，但在脂肪组织和骨代谢中也有作用。GIP与GLP-1同属肠促胰素家族，两者在血糖调控和能量代谢中发挥互补作用。目前该赛道已有礼来的替尔泊肽（Tirzepatide）获批上市，恒瑞医药的RS-9531申请上市，博瑞医药的BGM0504完成III期，众生睿创的RAY1225在II期取得24周减重21.18%的积极数据等。 GLP-1R / GCGR GLP-1R与GCGR协同激活，是多靶点策略中另一条已获临床验证的重要方向。GCGR是胰高血糖素受体，其内源性配体GCG由胰岛α细胞分泌，其主要作用为在机体血糖较低时通过促进肝糖原分解和糖异生来升高血糖。近年研究发现，外源性GCG可减少肝脏甘油三酯合成、促进肝脏脂解，增加产热提高全身能量消耗。GLP-1与GCG的连用形成了一种互补机制：GLP-1R激动促进降糖、抑制食欲和延缓胃排空，GCGR激动促进糖原与脂肪分解。目前该赛道已有多款分子进入临床后期。信达生物的玛仕度肽（Mazdutide）获批上市，勃林格殷格翰的Survodutide在II期试验中46周平均减重18.7%；阿斯利康的Cotadutide（MEDI0382）在临床前验证了减重与肝脏获益。国内四环医药旗下惠升生物的P052注射液已获批IND，临床前数据效果优于司美格鲁肽。 GLP-1R / GIPR / GCGR GLP-1R/GIPR/GCGR三靶组合中，前两者负责抑制食欲、延缓胃排空、促胰岛素分泌、平稳控制血糖，GCGR则提升基础代谢、加速内脏脂肪分解、降低甘油三酯与炎症水平。目前该赛道中，礼来的Retratrutide已进入III期临床，48周平均减重24.2%。国内方面，联邦制药与诺和诺德联合开发的UBT251已完成中国II期临床。翰宇药业的HY3003已完成临床前研究。歌礼的ASC3于2025年11月启动临床开发。恒瑞医药HRS-4729于2026年8月获国家药监局临床试验批准。 GLP-1R / FGF21 及更高阶组合 FGF21 主要由肝脏分泌，可改善胰岛素敏感性、减少肝脂肪、改善脂代谢。引入FGF21靶点的核心目的是直接靶向肝脏代谢与纤维化。目前常见的研发管线有GLP-1R / FGF21R 双靶点激动剂（如东阳光的HEC88473，质肽生物的ZT003）、GLP-1R/GCGR/FGF21R（如华东医药旗下道尔生物的DR10624）、GLP-1R/GIPR/FGF21R三靶点激动剂（如上海民为生物的MWN105）等。上述药物的临床前验证均高度依赖动物模型。南模生物自主研发的hGCGR/hGLP1R、hGLP1R / hGIPR双靶点、hGLP1R /hGIPR / hGCGR、hFGFR1/hGIPR/hGLP1R等多靶点人源化小鼠，在基因层面精准模拟了药物在人体的作用靶点，是加速该类双靶点药物临床转化落地的关键工具。 hGCGR/hGLP1R小鼠（NM-HU-233747）验证数据 Fig. 1 Body weight change of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. The hGCGR/hGLP1R mice were fed CD or HFD. PBS or Cotadutide was administered subcutaneously once daily until euthanasia. (A) Body weight, (B) body weight change and (C) Food intake per mouse were recorded (n=6, Mean ± SEM, ***p<0.001, Group2 vs. Group3). Abbr: CD, chow diet. HFD, high-fat diet. Fig. 2 Fat mass and lean mass changes of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. The hGCGR/hGLP1R mice were fed CD or HFD. PBS or Cotadutide was administered subcutaneously once daily until euthanasia. At the study endpoint, fat and lean mass were determined. (n=6, Mean ± SEM, *p<0.05, ***p<0.001). Abbr: CD, chow diet. HFD, high-fat diet. Fig. 3 Liver triglyceride, cholesterol content and blood glucose levels of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. The hGCGR/hGLP1R mice were fed CD or HFD. PBS or Cotadutide was administered subcutaneously once daily until euthanasia. (n=6, Mean ± SEM, *p<0.05, **p<0.01). Abbr: CD, chow diet. HFD, high-fat diet. Fig. 4 Adipose tissue weight of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. The hGCGR/hGLP1R mice were fed CD or HFD. PBS or Cotadutide was administered subcutaneously once daily until euthanasia.(n=6, Mean ± SEM, **p<0.01, ***p<0.001). Abbr: CD, chow diet. HFD, high-fat diet. Fig. 5 Oxygen consumption, carbon dioxide production, respiratory exchange ratio and heat production of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. The hGCGR/hGLP1R mice were fed CD or HFD. PBS or Cotadutide was administered subcutaneously once daily until euthanasia. Mice were housed in individual metabolic cages. (n=6, Mean ± SEM, ***p<0.001). Abbr: CD, chow diet. HFD, high-fat diet. 上下滑动查看 hGLP1R/hGIPR/hGCGR小鼠（NM-XA-240884）验证数据 Fig. 1 The efficacy of retatrutide in of HFD-induced hGLP1R/hGIPR/hGCGR mice. The hGLP1R mice were fed CD or HFD. The hGLP1R/hGIPR/hGCGR mice were fed CD or HFD. Saline or retatrutide was administered subcutaneously once daily until euthanasia. GLP1R相关人源化小鼠除上述介绍外，南模生物还可以提供多种围绕GLP1R靶点的人源化小鼠，匹配新一代GLP-1R药物研发需求。表1. GLP1R相关人源化小鼠相关阅读报名通道 | 直播：GLP-1之后，下一代代谢药物的机会在哪里？代谢药物创新论坛引领代谢研究新未来，这些小鼠模型不容错过！代谢研究常用Cre工具鼠：从疾病类型到基因机制保肌减脂时代开启：MSTN靶点在减重赛道重获新生 >>> 点击进入药靶百科合集参考文献： [1] Kusminski C, Perez-Tilve D, Müller T, Transforming obesity: The advancement of multi-receptor drugs Cell, 187, 3829-3853 关于我们上海南方模式生物科技股份有限公司（Shanghai Model Organisms Center, Inc.，简称"南模生物"），成立于2000年9月，是一家上交所科创板上市高科技生物公司（股票代码：688265），始终以编辑基因、解码生命为己任，专注于模式生物领域，打造了以基因修饰动物模型研发为核心，涵盖多物种模型构建、饲养繁育、表型分析、药物临床前评价等多个技术平台，致力于为全球高校、科研院所、制药企业等客户提供全方位、一体化的基因修饰动物模型产品解决方案。欢迎通过以下方式联系我们： 💬 微信公众号「南模生物SMOC」在线咨询 📞 拨打400-728-0660 📧 发送邮件至marketing@modelorg.com 🔗 点击文末「阅读原文」即可查看更多数据

2026-08-18

·百奥万思

减重从「一根针」到「一颗药」：礼来、诺和诺德、恒瑞的口服之战，新一代口服减肥药研发进展

过去一年 GLP-1 领域真正的分水岭，是一批口服小分子 GLP-1密集冲过临床终点。传统多肽类 GLP-1（司美格鲁肽、替尔泊肽）需注射、常需冷藏、规模化生产成本高、供应长期紧张。而小分子（非肽类）口服 GLP-1 是化学合成的小分子，可口服、无需空腹、不受饮食饮水限制、更易大规模供应——把 GLP-1 从"学注射、守服药规矩"变成"每天一颗药"，对怕针、对生活节奏敏感、需长期维持的人群意义重大。当前格局礼来 orforglipron（Foundayo）已于 2026 年 4 月获 FDA 批准，是全球首个获批的口服小分子 GLP-1；恒瑞、阿斯利康、歌礼等口服小分子密集读出三期/二期数据；多肽类口服司美（Wegovy 口服片）也已在美国/英国获批减重适应症。关键定位：口服小分子目前减重幅度约 10%–12%（约为替尔泊肽的一半、略低于注射司美），它走的是"够用 + 方便"路线，不追求"更强"。 8 款口服减重疗法，谁在领跑 2026？ 🧪 PART 01Aleniglipron 结构医药 Structure Therapeutics 2b 期 36 周最高减重 12.1%，真正的"化学药"路径机制 / 剂型每日一次口服小分子 GLP-1 受体激动剂，化学合成，可随餐或空腹服用。 12.1% 36周最高减重 10.4% 治疗相关停药率临床数据 2b 期 ACCESS 试验发表于《Nature Medicine》（2026）。230 名肥胖/超重成人、38 个美国中心、36 周。体重变化（自基线）：45 mg 组 −9.0%、90 mg 组 −10.7%、120 mg 组 −12.1%；安慰剂仅 −0.5%。安慰剂校正后额外减重：8.2% / 9.8% / 11.3%（各组 P<0.0001）。安全性：胃肠道反应多为轻-中度且随时间减轻；治疗相关停药率 10.4%；无药物性肝损伤病例。 ▸ 下一步：进入三期临床；三期将进一步放缓剂量递增以提升耐受性。看点：与小分子注射/多肽口服相比，真正的"化学药"路径，制造天花板有望被打破。 🏆 PART 02Orforglipron / Foundayo 礼来 Eli Lilly 全球首个获批的口服小分子 GLP-1，已商业化落地机制 / 剂型 FDA 于 2026-04-01 批准用于慢性体重管理，是首款非肽类、对饮食饮水零限制的口服 GLP-1；英国 MHRA 于 2026-08-10 批准，英国成为欧洲首个批准国。 13.6% 最高减重(T2D·72周) 51.5% ≥15%减重(ATTAIN-1) 临床数据三期 ATTAIN 项目（共入组 >4500 人，72 周）：ATTAIN-1（无糖尿病）各剂量平均减重 7.5%–11.2%（安慰剂 2.1%），最高剂量约 12%；ATTAIN-2（合并 2 型糖尿病）最高剂量 72 周减重最高 13.6%。最高剂量下 ≥15% 减重比例：ATTAIN-1 达 51.5%、ATTAIN-2 达 44.2%；腰围最多减少 12.5 cm。最新亚组分析（ADA 第 86 届科学年会）：绝经各分期女性最高剂量均显著减重，ATTAIN-1 达 12.8%–14.4%、ATTAIN-2 达 8.9%–13.6%，填补了更年期体重管理证据空白。 ▸ 用法/可及：每日一次、无空腹限制；自付价约 149 美元/月起。看点：已商业化落地，是口服减重"从临床到处方"的第一个标杆。 🇨🇳 PART 03HRS-7535 / KAI-7535 恒瑞医药国产口服减重第一梯队，三期阳性、拟 2026 申报机制 / 剂型每日口服小分子 GLP-1 受体激动剂，无需空腹、无需注射。 11.1% 50周平均减重 3 项二期已同行评审临床数据三期 HARBOR-1（中国成人肥胖/超重）：2026-07-07 公布积极顶线数据。180 mg 组治疗 44 周平均减重 10.9%，第 50 周进一步升至 11.1%，且未出现减重平台期；120 mg 与 180 mg 两个剂量组均达到全部主要及关键次要终点。证据厚度（罕见地已有 3 项二期发表于同行评审）：肥胖二期（26 周，235 人）180 mg 组安慰剂校正减重 −6.87%；2 型糖尿病加用二期（16 周）HbA1c 降幅 1.19%–1.82%，48.7%–63.2% 患者达标 <7.0%；糖尿病肾病 SOLID-DKD：90 mg 组蛋白尿较安慰剂多降 32%；糖尿病三期 OUTSTAND-2 达非劣效于达格列净（最高剂量 32 周 HbA1c 降 1.68% vs 1.28%）。 ▸ 下一步：计划 2026 年内递交体重管理与 2 型糖尿病的上市申请，是进度领先的国产同类产品。看点：国产口服减重"第一梯队"，与礼来、阿斯利康同台竞争。 🔬 PART 04Elecoglipron 阿斯利康 AstraZeneca 二期登《柳叶刀》，"无需空腹"是差异化卖点机制 / 剂型每日口服小分子 GLP-1 受体激动剂。 11.8% VISTA 36周减重 1.9% SOLSTICE HbA1c降临床数据二期数据（ADA 2026 同步发表于《The Lancet》）：VISTA（肥胖人群，36 周）体重降幅 11.8%；SOLSTICE（2 型糖尿病，26 周）HbA1c 降低 1.9%。三期布局：已启动大规模 Eluminate 项目；其中 Eluminate-2 在糖尿病适应症中开展头对头对比口服司美格鲁肽。 ▸ 局限提示：减重适应症三期仅以安慰剂为对照，缺少与已上市口服 GLP-1（Foundayo、口服司美）的直接头对头数据，后续横向疗效对比将缺注册临床硬证据。看点：跨国药企重金押注口服赛道，"无需空腹服用"是其主要差异化卖点。 💊 PART 05ASC30 歌礼制药 Ascletis 全球三期启动，并亮出三靶点复方组合拳机制 / 剂型每日一次小分子口服 GLP-1 受体激动剂。 15.2% 三靶点复方7天减重(灵长类) 约4600 全球三期入组(人) 临床数据全球三期 AURORA（2026-08-03 FDA 获批启动）：AURORA-1（NCT07743463，无糖尿病，约 3003 人）+ AURORA-2（NCT07743450，合并 2 型糖尿病，约 1560 人），合计约 4600 人，72 周，维持剂量 20/40/60 mg。二期第 13 周安慰剂校正减重：20/40/60 mg 分别为 5.4% / 7.0% / 7.7%，未见肝脏安全信号。预计 2028 年三季度读出顶线数据，2028 年底美国 NDA、2029 年初欧洲 MAA。 ▸ 同类首创复方（临床前亮点）：口服小分子三靶点复方 ASC30_48_39FDC（GLP-1/GIP/胰淀素 SARA）在非人灵长类 7 天给药减重高达 15.2%，较双靶点复方相对提升最高 120%，由 GIP 成分 ASC48 驱动；口服选择性胰淀素受体激动剂 ASC39 在肥胖大鼠 6 天减重 6.0%，对标 eloralintide。看点：歌礼以"单靶点 + 多靶点复方"组合拳卡位，试图在 orforglipron 之后抢占口服减重市场。 💉 PART 06口服司美格鲁肽 / Wegovy 口服片诺和诺德 Novo Nordisk 口服阵营减重幅度最高 16.6%，但受依从性掣肘机制 / 剂型口服多肽 GLP-1（借助 SNAC 吸收增强剂），每日一次。 16.6% 64周平均减重 ≈30% 减重≥20%受试者临床数据关键临床（OASIS 4，64 周）：25 mg 每日一次，完全依从者平均减重 16.6%（安慰剂 2.7%）；约 30% 受试者减重 ≥20%。OASIS 1（更高剂量 50 mg，68 周）平均减重 −15.1%。监管与可及：美国 FDA 于 2025 年 12 月批准（首个获批减重的 GLP-1 口服药）；英国 MHRA 于 2026 年 6 月 11 日批准，7 月 6 日开通私立处方供应（1.5/4 mg 先行，9/25 mg 自 7 月 20 日）。 ▸ 局限（依从性痛点）：须晨起空腹、仅少量水送服、服药后 30 分钟方可进食/饮水/服其他药；真实世界完成率据部分数据仅约 16.6%。看点：减重幅度在口服阵营中最高，但"空腹 + 等待"的服药规矩是其最大软肋，也正因此小分子口服（免空腹）被视为更优解。 🧫 PART 07Survodutide（趋势）勃林格殷格翰 Boehringer 口服多肽双激动剂 2b 期 11.8%，印证整体提速机制 / 剂型口服多肽 GLP-1/胰高血糖素双激动剂方向。 11.8% 2b期36周减重临床数据 2b 期 36 周减重 11.8%，与前述口服多肽路线同属"多肽口服"分支，进一步印证口服减重整体提速。看点：作为"多肽口服"分支的代表，与 Wegovy 片共同说明：口服减重不只一条技术路线在跑。 🦾 PART 08"护肌"组合（趋势） Bimagrumab + 司美格鲁肽联用减重达 30.4%，直击 GLP-1"掉肌肉"痛点机制 / 剂型虽非纯口服减重药，但代表下一代方向：在 GLP-1 基础上叠加"护肌"机制。 30.4% 联用26周减重 ≈3× 约为单药三倍临床数据二期（发表于《Nature Medicine》，26 周）显示，司美单药减重 9.5%、bimagrumab 单药 10.4%，二者联用达 30.4%——约为单药三倍，且主动保护/增肌，直击 GLP-1 "掉肌肉"痛点。口服小分子与护肌机制的叠加组合，是下一阶段研发热点。看点：口服小分子与护肌机制的叠加组合，是下一阶段研发热点。 📊横向对比一览药物企业类型关键阶段 / 数据减重幅度空腹 Aleniglipron 结构医药小分子口服 2b 期（Nature Medicine）36 周 12.1% 无需 Orforglipron（Foundayo）礼来小分子口服 FDA/MHRA 已获批72 周 13.6%（T2D）无需 HRS-7535 恒瑞小分子口服三期阳性，拟 2026 申报50 周 11.1% 无需 Elecoglipron 阿斯利康小分子口服 2b 登《柳叶刀》，三期启动36 周 11.8% 无需 ASC30 歌礼小分子口服全球三期启动（4600 人）二期 13 周 7.7%* 无需口服司美（Wegovy 片）诺和诺德多肽口服美/英已获批64 周 16.6% 需要 Survodutide 勃林格多肽口服 2b 期36 周 11.8% 待定 * ASC30 为二期 13 周安慰剂校正数据，长期数据有待三期读出。 🔍 REALITY CHECK必须看清的四个真相 ⚠️ 真相 1 减重幅度仍低于强效针剂：口服小分子约 10%–12%，约为替尔泊肽（最高约 22.5%）的一半；BMI 高、合并多种代谢问题且目标减重幅度大者，强效双靶点针剂仍是"天花板"。 ⚠️ 真相 2 副作用仍是同一类：口服小分子同属 GLP-1 机制，恶心、呕吐、腹泻、便秘等胃肠道反应最常见，多为轻-中度、随剂量递增缓解；不要因"是药片"就以为更温和。 ⚠️ 真相 3 长期安全性数据仍在积累：注射 GLP-1 已有超 5000 万患者年暴露，口服小分子大规模长期真实世界数据相对年轻，胰腺炎、胆囊、甲状腺等风险需持续随访。 ⚠️ 真相 4 停药依然可能反弹：口服不改变"停药后体重可能回升"的基本规律；JAMA 子刊事后分析显示替尔泊肽成功减重者停药一年超 80% 反弹至少 25%。 ✨写在最后 2026 年减重方式正从"一根针"走向"一颗药"。口服小分子 GLP-1（orforglipron已上市、HRS-7535/ASC30/Elecoglipron/Aleniglipron 密集推进）凭借"免注射、免空腹、易供应"重塑可及性；多肽口服（Wegovy 片）则守住"最高减重幅度"但受依从性掣肘。对怕针、需长期维持的人群，口服方案意义重大；但选药仍须医生结合个体目标体重缺口、合并症与耐受性综合判断，并配合高蛋白饮食与抗阻训练以保肌、防反弹。 📌本期关键词口服GLP-1小分子口服礼来 orforglipron恒瑞 HRS-7535歌礼 ASC30诺和诺德口服司美多肽口服三靶点复方护肌组合免空腹减重幅度 💊减重前沿观察持续追踪：口服减重｜GLP-1｜小分子口服｜多肽口服｜三靶点复方每周带你看懂减重赛道正在发生什么。关注 · 收藏 · 转发汇编时间：2026-08-17 ｜信息来源：Nature Medicine、The Lancet、FDA/NMPA/MHRA 监管公告、企业公告及行业媒体公开报道。本文为研发进展科普梳理，不构成医疗或投资建议；用药请遵医嘱并以监管最新指引为准。 #口服减重#GLP-1#小分子口服#礼来#恒瑞#歌礼#诺和诺德#多肽口服#三靶点复方#护肌组合#减重 END 本文信息均来源于公开报道及公司公告，欢迎转发分享，转载请注明出处。 📎 关注我们，获取每日生物医药前沿深度资讯 —— 本报告仅供信息参考，不构成投资建议 ——

100 项与索弗度肽相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
肝纤维化	临床3期	美国	Boehringer Ingelheim GmbH	2024-10-14
肝纤维化	临床3期	中国	Boehringer Ingelheim GmbH	2024-10-14
肝纤维化	临床3期	日本	Boehringer Ingelheim GmbH	2024-10-14
肝纤维化	临床3期	阿根廷	勃林格殷格翰（中国）投资有限公司	2024-10-14
肝纤维化	临床3期	阿根廷	Boehringer Ingelheim GmbH	2024-10-14
肝纤维化	临床3期	澳大利亚	Boehringer Ingelheim GmbH	2024-10-14
肝纤维化	临床3期	奥地利	Boehringer Ingelheim GmbH	2024-10-14
肝纤维化	临床3期	比利时	Boehringer Ingelheim GmbH	2024-10-14
肝纤维化	临床3期	巴西	Boehringer Ingelheim GmbH	2024-10-14
肝纤维化	临床3期	保加利亚	Boehringer Ingelheim GmbH	2024-10-14

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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


NCT06066515 (SYNCHRONIZE-1, Pubmed \| N Engl J Med)	临床3期	肥胖	725	Survodutide 3.6 mg	製憲壓淵淵鹹鏇網淵艱(窪製壓夢選蓋齋醖顧壓) = 顧餘艱簾鑰觸窪衊鹽鏇選襯築鏇遞憲鹽蓋糧築 (憲顧壓獵糧鏇積簾觸蓋, -13.6 ~ -10.8) 更多	积极	2026-06-07
				Survodutide 6.0 mg	製憲壓淵淵鹹鏇網淵艱(窪製壓夢選蓋齋醖顧壓) = 選餘積製網選願醖願糧選襯築鏇遞憲鹽蓋糧築 (憲顧壓獵糧鏇積簾觸蓋, -14.4 ~ -11.6) 更多
NCT04771273 (NASH_TAG2026)	临床2期	代谢功能障碍相关脂肪性肝炎 \| 纤维化 alanine aminotransferase \| liver stiffness measurement \| enhanced liver fibrosis ... 更多	295	Survodutide 2.4 mg	窪襯糧選齋壓積鬱獵鬱(襯網範構網憲選選廠範) = 簾鏇膚繭繭鬱範餘夢齋壓鏇繭選糧齋鹹憲憲鑰 (網鹽蓋壓齋艱積鏇衊範 ) 更多	积极	2026-02-04
				Survodutide 4.8 mg	-
NCT04771273 (1404-0043, CTgov)	临床2期	代谢功能障碍相关脂肪性肝炎	295	Survodutide (Survodutide 2.4 mg - Planned Maintenance Treatment)	襯夢獵窪構餘鑰繭壓鏇 = 積鏇構鬱齋鬱齋衊繭鹽獵糧鬱觸糧淵憲憲廠齋 (觸蓋廠顧憲齋築簾範醖, 網壓窪廠選積夢範廠衊 ~ 顧憲齋獵鏇憲獵鹹醖壓) 更多	-	2024-12-03
				Survodutide (Survodutide 4.8 mg - Planned Maintenance Treatment)	襯夢獵窪構餘鑰繭壓鏇 = 製顧簾窪蓋範壓淵獵簾獵糧鬱觸糧淵憲憲廠齋 (觸蓋廠顧憲齋築簾範醖, 遞遞製膚衊鏇積鬱鏇鬱 ~ 醖獵膚廠衊獵簾簾膚築) 更多
ESC2024	临床2期	肥胖	387	Survodutide 4.8 mg	糧積膚顧廠鹽製淵築淵(糧鬱憲襯壓廠簾艱衊鬱) = 襯蓋廠築願積餘蓋顧網築艱衊壓顧鬱鹹膚鏇齋 (淵鹹壓醖遞醖壓範製製 )	积极	2024-09-01
NCT04153929 \| NCT04667377 \| NCT03591718 (1665-P, ADA2024)	临床1/2期	2型糖尿病 \| 肥胖 HbA1c \| insulin sensitivity \| glucose biomarkers ... 更多	-	Survodutide	憲蓋窪窪淵齋願製製窪(製窪選壓衊齋壓壓簾廠) = 0.4 vs 0.0 獵蓋衊壓鏇選衊觸築築 (簾鑰窪鑰窪廠鹹廠觸壓 ) 更多	积极	2024-06-14
				Placebo
NCT04771273 (1404-0043, Pubmed)	临床2期	代谢功能障碍相关脂肪性肝炎	293	Survodutide 2.4 mg	鏇鏇醖積齋製鑰網願範(艱鹽壓簾繭遞醖憲鑰夢) = 鏇顧膚範積襯簾鏇構觸鬱鹽簾鑰築鑰糧鹹窪鑰 (壓艱製簾製簾窪糧壓構 ) 更多	积极	2024-06-07
				Survodutide 4.8 mg	鏇鏇醖積齋製鑰網願範(艱鹽壓簾繭遞醖憲鑰夢) = 鏇憲蓋淵遞衊範鹽壓鹹鬱鹽簾鑰築鑰糧鹹窪鑰 (壓艱製簾製簾窪糧壓構 ) 更多
NCT04667377 (Phase II Trial, ENDO2024)	临床2期	超重 \| 肥胖	384	Survodutide 4.8 mg	襯廠網餘顧廠鹽膚夢築(蓋憲選鹹獵觸網壓鹹衊) = 鏇選憲簾鹹襯糧壓糧遞繭積繭選顧製憲餘廠壓 (艱繭襯選廠憲蓋鬱膚艱 )	积极	2024-06-01
				Placebo	襯廠網餘顧廠鹽膚夢築(蓋憲選鹹獵觸網壓鹹衊) = 選膚網範鏇觸鹽鏇鬱製繭積繭選顧製憲餘廠壓 (艱繭襯選廠憲蓋鬱膚艱 )
NCT04771273 (Corporate Publications) 人工标引	临床2期	代谢功能障碍相关的脂肪肝病	295	Survodutide	壓範醖醖鬱積繭範鬱築(構襯糧蓋鏇壓窪遞膚憲) = 蓋餘鹹鹽醖遞鬱遞淵顧構選遞鏇鏇顧壓鏇網齋 (窪憲鹹顧遞艱餘鬱廠鏇 ) 达到	积极	2024-02-26
				placebo	壓範醖醖鬱積繭範鬱築(構襯糧蓋鏇壓窪遞膚憲) = 夢簾鏇憲獵鹹鹽製淵糧構選遞鏇鏇顧壓鏇網齋 (窪憲鹹顧遞艱餘鬱廠鏇 ) 达到
NCT04771273 (GlobeNewswire) 人工标引	临床3期	代谢功能障碍相关脂肪性肝炎	-	survodutide	憲簾願鏇網簾製遞衊築(鹽範壓繭鏇壓齋鏇膚廠) = 鏇構鏇鑰糧製壓遞築蓋蓋繭鏇製餘鹹願選簾範 (餘廠築壓鏇壓醖蓋鹹獵 ) 达到	积极	2024-02-26
				Placebo	憲簾願鏇網簾製遞衊築(鹽範壓繭鏇壓齋鏇膚廠) = 壓築網構網獵壓簾網蓋蓋繭鏇製餘鹹願選簾範 (餘廠築壓鏇壓醖蓋鹹獵 ) 达到
NCT04667377 (Phase II Trial, CTgov)	临床2期	肥胖	387	BI 456906 (0.6 mg BI 456906 - Planned Maintenance Treatment (Maintenance Dose Assigned at Randomisation))	範衊夢築鑰顧鬱觸範簾(糧齋範鏇窪鹽壓夢繭艱) = 願積範積壓繭醖鏇獵顧鑰窪簾窪顧築廠餘鏇顧 (壓製願廠廠積醖衊鑰壓, 1.07) 更多	-	2023-11-02
				BI 456906 (2.4 mg BI 456906 - Planned Maintenance Treatment)	範衊夢築鑰顧鬱觸範簾(糧齋範鏇窪鹽壓夢繭艱) = 憲製鹽繭壓蓋醖遞醖糧鑰窪簾窪顧築廠餘鏇顧 (壓製願廠廠積醖衊鑰壓, 1.01) 更多