Lixisenatide

在医药领域的漫长征途中，总有一些药物如星辰般耀眼夺目。二甲双胍，这个名字在医药界被反复提及，它不仅在糖尿病治疗领域坚守数十年，还闪耀着心血管保护、抗衰老等多重潜在价值的光芒，堪称“神药”典范。如今，新的希望破土而出，GLP-1类减肥药正崭露头角，沿着二甲双胍的轨迹，散发着独特魅力。近期，《Nature》杂志的一篇报道掀起波澜，一项临床试验聚焦于GLP-1类减肥药利拉鲁肽，发现其对偏头痛有意想不到的治疗潜力。当GLP-1攻向偏头痛《Nature》发表这项关于偏头痛的研究，由丹麦南安普敦大学Lanfranco Pellesi团队主导，共有38名患者参与，最终纳入分析的有31名患者，其中女性占比83.9%。这些患者均为慢性偏头痛合并肥胖患者，且此前至少尝试过两种预防性药物但均告失败。在12周的治疗期间，患者接受每日一次的利拉鲁肽注射。结果显示，治疗后患者的平均每月头痛天数从基线时的19.8天显著下降至10.7天，平均减少了9.1天，这一差异具有统计学意义。具体而言，48%的患者（15人）每月头痛频率减少了50%以上，其中7人的头痛频率降低了75%或更多，还有1名患者的头痛症状完全消失。图片来源：headachejournal.onlinelibrary更令人惊喜的是，在观察周期内患者的体重指数仅从34.0±2.3kg/m²微降至33.9±2.3kg/m²，这种微弱的体重变化并未达到统计学显著性，意味着药物对偏头痛的改善作用可能独立于减重效应。研究人员推测，颅内压力的轻微升高可能是偏头痛发作的原因之一，而GLP-1受体激动剂可减少脑脊液分泌，已被证明可有效治疗特发性颅内高压。他们假设利拉鲁肽可能通过降低颅内压，抑制导致偏头痛的皮质和三叉神经敏化，从而发挥治疗作用。尽管该研究存在局限性，如未检测颅内压、空腹血糖水平或血红蛋白A1c，缺乏随机分组及安慰剂对照，研究人群限定为肥胖且难治性偏头痛患者等，但这一发现无疑为偏头痛治疗领域开辟了新的研究方向。百亿美元市场偏头痛是一种常见的慢性神经血管性疾病，全球约有超10亿患者，其反复发作的特性对患者的生活质量造成了严重影响，也带来了沉重的经济负担。数据显示，2022年全球偏头痛市场的整体价值达到96亿美元，预计到2027年将增长至175亿美元，期间的复合年增长率为9.4%。这一增长趋势主要得益于新型药物的研发和应用，尤其是靶向降钙素基因相关肽（CGRP）的药物。图片来源：小药说药CGRP在偏头痛的发病机制中起着关键作用，因此成为药物研发的重要靶点。目前，全球已经批准了多款CGRP受体拮抗剂，包括单克隆抗体和小分子拮抗剂。其中，小分子拮抗剂主要用于急性偏头痛的治疗，而单克隆抗体则主要用于慢性偏头痛的预防。2021年，礼来的Galcanezumab以5.77亿美元的销售额成为畅销的CGRP药物，Allergan的Ubrogepant以5.52亿美元的销售额紧随其后。同时，CGRP拮抗剂的使用增加也将推动预防偏头痛领域的发展，预计到2027年，预防性偏头痛市场的价值将达到101亿美元，复合年增长率为11.3%。急性偏头痛市场则主要受到Nurtec、Ubrelvy和Zavzpret等药物临床应用增加的推动，预计将以7.2%的复合年增长率增长。除了CGRP靶向药物，曲坦类药物作为传统的偏头痛治疗药物，仍然在市场上占据重要地位。这类药物通过增加大脑中的血清素水平，减少炎症并收缩血管，从而有效缓解偏头痛症状。多领域潜力挖掘GLP-1受体激动剂是一类具有多重作用的药物，最初用于2型糖尿病的治疗。在血糖控制方面，其通过刺激胰岛素分泌、抑制胰高血糖素分泌以及延缓胃排空等机制来降低血糖水平，度拉糖肽、司美格鲁肽等在临床上广泛应用。随着研究深入，这类药物的心血管获益逐渐被发现，例如利拉鲁肽于2017年8月获FDA批准用于降低2型糖尿病患者的心血管风险，司美格鲁肽和度拉糖肽也分别在2020年1月和2月获批类似适应症。2025年1月，司美格鲁肽更是首次进入糖尿病肾病综合管理领域，获批用于降低合并慢性肾病的2型糖尿病患者肾脏功能恶化、终末期肾病及心血管死亡风险，进一步拓展了其在糖尿病并发症防治方面的作用。除了在糖尿病领域的广泛应用，GLP-1受体激动剂在体重管理方面也展现出显著优势。利拉鲁肽、司美格鲁肽、替尔泊肽等药物获批用于肥胖症治疗，其通过减少食物摄入和降低食欲来帮助患者减轻体重，为肥胖患者带来了新的治疗选择。在其他疾病领域，GLP-1受体激动剂的研究也在不断拓展。虽然目前尚未被FDA批准用于治疗1型糖尿病，但有研究显示其在降低HbA1c和减轻体重方面具有一定潜力，部分医疗提供者会根据患者情况超说明书使用。在阿尔茨海默症治疗方面，司美格鲁肽等药物正在开展相关适应症的临床试验，有望为这一疑难病症带来新的希望。此外，利司那肽与利拉鲁肽已进入帕金森病治疗的II期临床，为帕金森病患者提供了潜在的新疗法。部分GLP-1药物也已完成射血分数保持的心力衰竭适应症的III期临床，如司美格鲁肽，或将为心力衰竭患者带来新的治疗选择。结语GLP-1受体激动剂的发现与应用，为众多疾病领域的治疗带来了新希望。从2型糖尿病的血糖控制与心血管保护，到体重管理、肥胖症治疗以及偏头痛防治，其展现出的潜力令人瞩目。随着研究的不断深入，GLP-1受体激动剂将在更多疾病的治疗中发挥关键作用，为人类健康福祉添砖加瓦。参考来源：1.https://mp.weixin.qq.com/s/DfDm6DtcjOuqq4M6_-WQMQ2.https://mp.weixin.qq.com/s/z2lwt98xFecOYuPuVYllcw3.https://mp.weixin.qq.com/s/6nf40x5VrWkMENTeSg6Q9w声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 史蒂文合作、投稿、转载开白 | 马老师 18323856316（同微信） 阅读原文，是受欢迎的文章哦

London: Adding Roche's immunotherapy drug Tecentriq to chemotherapy after surgery in certain patients whose colon cancer had spread to the lymph nodes led to a 50 per cent reduction in cancer recurrence and death compared to chemotherapy alone, according to trial data presented at recent medical meeting. Patients in the study had tumors with a genetic defect known as deficient DNA mismatch repair, or dMMR. About 15 per cent of colon cancer patients have dMMR tumors , which do not respond well to chemotherapy. "The findings from our study represent a major advance in the adjuvant treatment of dMMR stage 3 colon cancer and will now change the treatment for this type of cancer," study leader Dr. Frank Sinicrope of the Mayo Clinic in Rochester, Minnesota said in a statement. The data were presented at the ASCO meeting that concluded earlier this week. The trial enrolled 712 patients with dMMR stage 3 colon cancer that had been surgically removed and who had cancer cells in their lymph nodes. Half of the study participants received chemotherapy along with Tecentriq, which activates the immune system to attack and kill cancer cells, for six months, followed by the immunotherapy alone for another six months. The other half of the patients received chemotherapy for 12 months. The benefit of Tecentriq was seen even in the oldest patients and those at particularly high-risk. "It's extremely rewarding to be able to offer our patients a new treatment regimen that can reduce the risk of recurrence and improve their chances of survival," Sinicrope said. ASPIRIN MAY NOT BE BEST LONG-TERM OPTION AFTER HEART PROCEDURE As patients recover after a minimally invasive heart procedure, they might be better off continuing to take a certain type of blood-thinning drug to help prevent a heart attack or stroke, instead of continuing with the traditional aspirin, a new study suggests. Early after percutaneous coronary intervention (PCI) - a procedure to prop open blocked arteries either after a heart attack, or to prevent one - patients often receive dual anti-clotting therapy with both a P2Y12 inhibitor such as clopidogrel, the generic version of Plavix, or AstraZeneca's Brilinta (ticagrelor), and aspirin. After several months, patients are usually switched from dual therapy to lifelong daily aspirin use. But pooled data looking at patients who took part in five earlier clinical trials found that continuing to prescribe the P2Y12 inhibitors and stopping the aspirin was associated with lower rates of death, heart attack and stroke compared with continuing the aspirin, with no increased risk of major bleeding, researchers reported in The BMJ. Overall, the trials involved 16,117 patients who received either a P2Y12 inhibitor or aspirin after completing dual therapy following PCI. After an average follow-up period of around 4 years, P2Y12 inhibitor therapy was associated with a 23% lower risk of a composite of heart-related death, heart attack, or stroke, compared with aspirin, with no significant difference in major bleeding. That translates into one prevented cardiovascular death, heart attack, or stroke for every 46 patients taking a P2Y12 inhibitor instead of aspirin after dual therapy. Overall, the findings suggest that P2Y12 inhibitor drugs should be preferred over aspirin "due to reductions in major adverse cardiac and cerebrovascular events without increasing major bleeding in the medium term," according to an editorial published with the study. But the editorial said that since patients are advised to continue the post-PCI therapy for life, large trials directly comparing the different strategies with longer follow up are needed. LONG-TERM GLP-1 USE LINKED TO HIGHER RISK OF AGE-RELATED EYE DISEASE Some diabetes and weight-loss drugs from the class known as GLP-1 agonists were linked with a small but elevated risk for an age-related eye disease in patients with diabetes, according to a study published on Thursday in JAMA Ophthalmology. In 139,000 patients with diabetes, including 46,334 who had been using the GLP-1 drugs semaglutide or lixisenatide, researchers identified 181 new cases of neovascular age-related macular degeneration, also known as wet AMD. Wet AMD is a degenerative eye disease marked by the abnormal growth of blood vessels under the retina that leak fluid or blood and can lead to blindness. The risk of developing AMD during up to three years of follow-up was low, at 0.2% in GLP-1 users versus 0.1% in non-users. Still, the researchers point out, after accounting for patients' individual risk factors, the odds of AMD were doubled with at least six months of GLP-1 use and tripled in patients with the longest duration of use. Semaglutide is the active ingredient in the widely used Novo Nordisk drugs Ozempic and Wegovy, while lixisenatide is the main ingredient in Sanofi's discontinued Adlyxin. GLP-1 drugs have also been associated with higher risks for an eye condition known as nonarteritic anterior ischemic optic neuropathy, or NAION. Researchers did not have information about the dose, route of administration, or frequency of administration of the medications used in the study. Even with that information, the study could not have proved cause and effect. At least one earlier study with longer follow up reported that GLP-1 use was linked with a lower, rather than higher, risk for AMD. "Our findings are not directly contradictory" with that earlier report, said study leader Dr. Reut Shor of the University of Toronto. "Factors such as timing and duration of exposure, disease stage, and patient characteristics may all influence outcomes," Shor said. "Our results add another layer to the emerging understanding of this complex relationship and emphasize the need for further research to clarify these trends." (To receive the full newsletter in your inbox for free sign up here) (Reporting by Nancy Lapid; additional reporting by Shawana Alleyne-Morris; editing by Bill Berkrot)