Enicepatide

2026年6月，国际顶刊《自然综述・药物发现》发表题为《肥胖药物研发格局演变》的全景式综述，系统梳理了肥胖治疗从 “靠毅力” 到 “精准用药” 的百年突破，详解了从 GLP1 单靶点到三受体激动剂、口服小分子的迭代历程，揭示了当前行业的核心瓶颈与未来方向。 一、从 “彩虹药丸” 到 GLP1：肥胖药的百年逆袭 全球肥胖人口已超 10 亿，预计 2035 年将达 19 亿，占全球总人口 25%。长期以来 “吃多动少” 的片面认知，让肥胖被污名化为 “意志力问题”，但事实上，肥胖是遗传、神经内分泌、环境共同驱动的慢性复发性疾病，单纯生活干预对 90% 以上人群无法实现长期减重。 上世纪的 “彩虹药丸”（中枢食欲抑制剂）虽能减重，但伴随严重的心血管和精神副作用，多数已退市。直到 2021 年司美格鲁肽获批肥胖适应症，肥胖治疗才迎来真正的转折点：它通过模拟肠道分泌的 GLP1 激素，作用于大脑摄食中枢抑制食欲，实现了 10%-15% 的平均减重，且安全性大幅提升。 图1 多肽类减肥药分子构型分类二、多受体时代：减重突破 20% 的核心密码 如今肥胖药已进入 “多受体协同” 的黄金时代，一个分子同时激活 2-3 条减重通路，疗效实现质的飞跃： GLP1/GIP 双激动剂：替尔泊肽是代表，平均减重 15%-20%，优于司美格鲁肽，还能降低 94% 的糖尿病发病风险；罗氏 CT-388 更是创下 48 周减重 22.5% 的纪录。 三受体激动剂：瑞替鲁肽同时激活 GLP1/GIP/ 胰高血糖素受体，48 周平均减重 22.1%，近半数患者减重超 25%，还能显著缓解肥胖导致的膝关节疼痛。 胰淀素类药物：诺和诺德的 Zenagamtide 作为 GLP1 + 胰淀素融合分子，36 周皮下注射减重 23.9%，口服剂型 12 周也能减重 11.8%，是目前减重效果最强的候选药。 图2 主流药物安慰剂校正减重曲线 口服剂型的突破更是大幅提升了用药便利性：口服司美格鲁肽 25mg 已获批，每日一次；礼来的奥福格列平作为全球首个口服小分子 GLP1 激动剂，无需空腹、无饮食限制，72 周减重 11.5%，2026 年刚获 FDA 批准。 表1 临床阶段胰淀素类候选药物 三、不止减肥：一张图看懂全系统获益 这些药物的价值远不止减重，它们能跨系统改善 20 多种肥胖相关并发症： 心血管：司美格鲁肽已获批降低肥胖人群主要不良心血管事件风险； 肝脏：司美格鲁肽获 FDA 加速批准用于非酒精性脂肪肝（MASH）； 肾脏：司美格鲁肽可延缓慢性肾病进展； 其他：替尔泊肽获批阻塞性睡眠呼吸暂停，还在开展银屑病、酒精成瘾、阿尔茨海默病等适应症临床。 图3 GLP1 系列药物拓展适应症图谱四、下一代新药：精准、靶向、保肌肉 综述重点介绍了三大前沿研发方向： 精准医疗：通过基因检测、多组学分析将肥胖分为 “食欲亢进型”“能耗偏低型”“肌肉易流失型”，匹配不同机制药物，摆脱 “一刀切”。 多肽 - 药物偶联物（PDC）：以 GLP1 为 “导航”，将小分子药物精准递送到肝脏、脂肪等靶器官，降低全身副作用。 保肌肉联合方案：GLP1 类药物减重中约 25%-40% 是肌肉流失，联用肌抑素抑制剂可让 92.8% 的减重来自脂肪，II 期试验中司美格鲁肽 + Bimagrumab 平均减重 22.1%，几乎保全肌肉。 图4 肥胖精准医疗分层架构图 5 PDC 靶向作用机理五、四大核心挑战：离 “减肥神药” 还有多远 尽管进展显著，行业仍面临四大无法回避的难题： 停药反弹：这是最大痛点。人体存在 “体脂设定点”，停药后会代偿性升高食欲、降低能耗，几乎所有药物停药后体重都会快速反弹，目前只能靠长期用药维持。 个体疗效差异：合并 2 型糖尿病的患者，同一款药物减重幅度普遍比单纯肥胖者低 30%-40%。 长期安全性：多数新药缺乏 10 年以上的长期随访数据，胃肠道副作用、心率变化、精神影响仍需监测。 可及性：原研药价格高昂，限制了全球普及。 图5 停药后体重变化三类模型六、未来展望：从终身用药到功能性治愈 综述指出，肥胖药物的终极目标是实现 “功能性治愈”—— 即停药后体重不反弹。未来 5-10 年，随着 AI 药物设计、多组学精准分型、靶向递送技术的成熟，以及国产创新药的密集上市，我们有望迎来更安全、更有效、更普惠的新一代减肥药，真正终结全球肥胖大流行。 表2 处于临床试验的口服肥胖药物汇总 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

iStock, Larry Gibson The American Diabetes Association’s annual congress will feature a superstar lineup, including weight loss giants Eli Lilly and Novo Nordisk. But several scrappy biotechs will also present obesity candidates with the potential to match—if not outperform—their deep-pocketed competitors. This weekend, many of the world’s leading metabolic experts will flock to New Orleans to attend the 2026 American Diabetes Association’s Scientific Sessions. Recent editions of the meeting have unsurprisingly had a heavy focus on obesity . Weight loss has become one of the most lucrative areas across biopharma, with IQVIA forecasting $92 billion in sales of obesity medicines this year and up to $200 billion by 2027 and beyond. And last year, obesity unseated long-reigning oncology as the top contributor of pharma pipeline value, with weight-loss medications accounting for 25% of the overall pharma pipeline value. Obesity’s ascent has spilled over into conferences like ADA, where many of the most highly anticipated presentations focus on weight control. This is especially true for the 2026 edition of the congress, which features a superstar lineup of companies presenting new data on both approved and investigational drugs. These include readouts from undisputed weight loss leaders Eli Lilly and Novo Nordisk, as well as from other major pharmas looking to stake their claim in the sector. But ADA 2026 will also see some plucky biotechs stand up to these giants, bringing their own obesity candidates that could give these deep-pocketed counterparts a run for their money. Frontrunners face off with next-gen obesity bets All eyes at ADA will be on Lilly and Novo and their next-generation assets as they chart the way forward for the obesity space. Lilly will present data from the Phase 3 TRIUMPH-1 and TRANSCEND-T2D-1 studies of its triple-G agonist retatrutide in obesity and diabetes, respectively. Lilly has deemed retatrutide part of a “different drug category,” as compared with its current weight-loss drugs, Andy Hsieh, healthcare research analyst at William Blair, told BioSpace in an email. Hsieh expects the triple-G asset, “given its high potency,” to set itself apart from Lilly’s other obesity products—including the GLP-1/GIP dual agonist Zepbound and small-molecule drug Foundayo. Still, he anticipates that the debate around retatrutide will focus on the tradeoff between its weight loss efficacy and tolerability. Indeed, data that Lilly has disclosed so far demonstrate impressive weight reduction. Retatrutide generated 28.3% weight loss over 80 weeks in the Phase 3 TRIUMPH-1 study, Lilly announced on May 21, likening the results to those elicited by bariatric surgery. The trial assessed the candidate in patients with obesity but without diabetes. The Phase 3 TRIUMPH-4 study, reported in December, showed a 26.6% placebo-adjusted weight-loss at 68 weeks in patients who have obesity or are overweight with knee osteoarthritis, results BMO Capital Markets said at the time “help to solidify retatrutide’s pro an even higher efficacy next generation GLP-1+ asset.” But the drug’s safety pro tempered some of the industry’s excitement, with Lilly reporting a signal called dysesthesia—a neurological anomaly characterized by unpleasant or painful sensations—in more than a fifth of patients on the 20-mg dose of retatrutide in TRIUMPH-4. Dysesthesia also occurred in TRIUMPH-1, with rates rising with dose level. Obesity Lilly’s Retatrutide Scores Triple Trial Triumph With 26% Weight Loss, But New Safety Signal Emerges Analysts were hoping for a safety pro to what was achieved in Phase II but an abnormal sense of touch, called dysesthesia, has emerged in the late-stage TRIUMPH-4 trial. December 11, 2025 · 3 min read · Annalee Armstrong Read more Not to be outdone by its chief competitor, Novo is bringing its own next-generation weight-loss candidate, CagriSema, to ADA 2026. The drug is a fixed-dose combination of its GLP-1 giant semaglutide and long-acting amylin analog cagrilintide. While the pharma will give several presentations at the conference, William Blair believes investors will be more interested in CagriSema’s data in diabetes—outlined in the Phase 3 REIMAGINE 1, 2 and 3 studies—than in obesity after the asset “failed to demonstrate non-inferiority” versus Lilly’s Zepbound , according to a May 4 note. In February, data from Novo’s head-to-head REDEFINE-4 study showed that patients on CagriSema lost 23% of their body weight on average at 84 weeks, whereas comparators on Zepbound saw a 25.5% reduction in weight. Novo remains confident in CagriSema, however, and expects the drug to hit U.S. shelves next year. “When CagriSema will make it to the market early next year as the first amylin-based product, it will have the best weight loss label than any product marketed at that time,” CEO Maziar Mike Doustdar told investors and analysts at the time of the head-to-head readout. Behind the duopoly, Big Pharmas play for third With Lilly and Novo firmly in the lead, the rest of biopharma is looking to claim that coveted third place, with Boehringer Ingelheim, Roche and more hustling to get their candidates to the market. Many of these aspirants will be at ADA 2026. Based on timelines alone, Hsieh told BioSpace , Boehringer appears poised to win the race. Boehringer is working with Zealand Pharma on survodutide, a dual agonist of the GLP-1 and glucagon receptors, “designed to go beyond weight reduction by targeting pathways relevant to metabolic dysfunction and liver disease,” Vani Manja, global head of Obesity and Liver Health at the German pharma, told BioSpace in an email. With survodutide, Boehringer is shifting its focus “from weight loss to metabolic health, from single targets to multi‑pathway approaches, and from short‑term outcomes to more durable impact,” Manja said. At ADA, the company will present detailed data from the Phase 3 SYNCHRONIZE-1 study, a topline readout from which showed a 16.6% drop in weight at 76 weeks, as compared with 3.2% in placebo controls. These numbers “appear less competitive vs other dual target mechanisms,” such as Lilly’s tirzepatide, BMO said in an April 28 note. Still, survodutide could set itself apart from the current leaders by offering better quality weight loss, BMO added. Indeed, most of the weight reduction in SYNCHRONIZE-1 was due to fat loss. Lean mass accounted for “only a small proportion” of the total weight that participants lost, Zealand said at the time. William Blair expects to see more detailed data from SYNCHRONIZE-1 at ADA, particularly “additional color from survodutide’s impact on body composition and liver fat,” according to the firm’s May 4 note. These findings, in turn, could have readthroughs to other indications, such as metabolic dysfunction-associated steatotic liver disease (MASH), which survodutide is also targeting, the analysts continued. Another potential third-placer is Roche. The pharma in late 2023 invested $2.7 billion to acquire Carmot Therapeutics and its pipeline of GLP-1 therapies, including CT-388, which additionally activates the GIP receptor. Phase 2 data for the asset in January demonstrated a 22.5% placebo-adjusted weight reduction at 48 weeks, with no signs of plateauing. Earnings Roche Plans To Go Toe-to-Toe With Novo, Lilly in Obesity Roche aims to become a “top three player” in obesity, Teresa Graham, CEO of the group’s Pharma unit, said Thursday during a presentation of the company’s full-year 2025 earnings. January 29, 2026 · 2 min read Read more More detailed data from the trial will be presented at ADA, where William Blair will be keeping an eye out for detailed tolerability data, “given the relatively high doses being evaluated,” analysts said on May 4. So far, Roche has only said that CT-388’s safety is “generally consistent with the incretin class of medicines.” The firm also believes that investors will also be interested in learning about Roche’s plans to combine CT-388 with Zealand’s amylin therapy petrelintide. Roche signed an up to $5.3 billion partnership in March 2025 with the Danish biotech for the asset. Also gaining ground on the leaders is Amgen, which according to Hsieh is just a bit behind Boehringer in terms of timing. When it comes to weight-loss numbers, Amgen might “have a better chance of catching up to the duopoly,” he said. Anchoring Amgen’s weight-loss portfolio is MariTide, a bispecific antibody-peptide that targets both GLP-1 and GIP pathways. In November 2024, the pharma released Phase 2 data showing an up to 20% drop in body weight at 52 weeks—findings analysts found disappointing . Amgen is nevertheless standing by MariTide. During the company’s earnings call in April, Murdo Gordon, executive vice president of global commercial operations, said MariTide has the potential “to be the best monthly or less frequently dosed agent” in obesity. In addition to weight loss, Amgen is positioning MariTide as a medicine for adjacent indications, such as heart failure, obstructive sleep apnea and elevated liver fat. “We see the future of care as increasingly connected across obesity and cardiovascular disease as these conditions commonly coexist and can lead to serious outcomes or death, even though they are treatable,” Chief Medical Officer Paul Burton told BioSpace in an email. Amgen will be at ADA 2026 but will not be presenting MariTide data. Earnings Amgen positions MariTide as potential ‘best monthly’ obesity drug Amgen has launched a late-stage program to test the feasibility of switching patients from weekly GLP-1 injections to its own investigational obesity asset MariTide, which could open up monthly or more infrequent dosing schedules. May 1, 2026 · 2 min read · Tristan Manalac Read more Don’t discount the little guys Obesity isn’t just an opportunity for the big guys, of course, as many smaller biotechs are also advancing promising candidates. Structure Therapeutics is working on the GLP-1 pill aleniglipron, a potential competitor to Lilly’s Foundayo and Novo’s oral Wegovy . In December 2025, Structure released data from the Phase 2b ACCESS II study, showing that a 120-mg dose of aleniglipron resulted in an 11.3% placebo-adjusted weight reduction at 36 weeks—findings that BMO in a Dec. 8 note called “highly competitive.” Additional data in March showed that at the 44-week follow-up, average weight loss improved even further to 16.3% on a placebo-adjusted basis. Structure will show up at ADA with a detailed presentation of ACCESS II, as well as data from the dose-ranging ACCESS study . The biotech will also have posters looking at a lower starting dose of aleniglipron and a combination regimen of the candidate paired with an amylin asset. Viking Therapeutics is similarly looking to play alongside the industry giants with its dual GLP-1/GIP agonist VK2735 , which the biotech is advancing both as a subcutaneous injection and as a daily pill. In his email to BioSpace , Hsieh also named VK2735 as one of the obesity hopefuls likely to catch up to Lilly and Novo, with a chance to potentially overtake Boehringer. At the recently concluded European Congress on Obesity last month, Viking presented data from the Phase 2 VENTURE-Oral study, touting placebo-adjusted weight reduction of up to 10.9% for patients on oral VK2735 at 13 weeks. Meanwhile, the weekly subcutaneous injection hit weight loss of up to 13.1% on a placebo-adjusted basis at the same time point, according to Phase 2 data presented in November 2024. Viking has pushed subcutaneous VK2735 into late-stage development, while the oral formulation is scheduled to enter Phase 3 studies later this year.