作者: Lübker, Christopher ; Lincoff, A. Michael ; Bøg, Martin ; Lingvay, Ildiko ; McEwan, Phil ; Toliver, Joshua C. ; Yeates, Florian ; Faurby, Mads ; Miller, Ryan ; Foos, Volker

AIMS:

The cardioprotective effects of semaglutide 2.4 mg reported in the SELECT cardiovascular (CV) outcomes trial (ClinicalTrials.gov NCT03574597) provide clinical benefit for subjects with overweight or obesity and established CV disease without type 2 diabetes (T2D). We assessed cost-effectiveness of semaglutide 2.4 mg in this population against the American College of Cardiology/American Heart Association value framework.

MATERIALS AND METHODS:

A cohort-level Markov-state cost-effectiveness model using trial-derived data with outcomes from a healthcare sector perspective measured over a lifetime horizon was developed. Treatment costs were based on US list prices; scenario analyses used literature-reported estimated rebates. Healthcare costs and benefits were discounted at 3.0%. A simulated cohort of 100,000 subjects was aligned to the SELECT trial population baseline characteristics and time-on-treatment. Subjects received either semaglutide 2.4 mg or placebo in addition to standard of care (SoC). Modelled outcomes included clinical events (CV events, progression to T2D, chronic kidney disease [CKD]) and health economic measures, including direct costs and quality-adjusted life years (QALYs).

RESULTS:

Mean semaglutide 2.4 mg treatment duration was 2.79 years. Per 100,000 subjects, treatment avoided 2,791 non-fatal myocardial infarctions, 3,000 coronary revascularizations, 487 non-fatal strokes, and 115 CV deaths over the modeled lifetime horizon. Average per-subject lifetime treatment costs were $47,353; savings arose from avoided T2D ($14,431), CKD ($2,074), and CV events ($1,512). Semaglutide 2.4 mg was associated with increased lifetime costs ($29,767), additional QALYs gained (0.218) and an incremental cost-effectiveness ratio of $136,271/QALY at list price; a scenario using an empirically estimated 48% rebate predicted $32,219/QALY.

LIMITATIONS:

The generalizability of observations from SELECT to a broader US population is unknown. Our model does not capture all outcomes nor costs that may be affected by weight loss. Modeling assumptions may present limitations.

CONCLUSIONS:

Semaglutide 2.4 mg use as in SELECT is cost-effective at list price, using a $150,000/QALY willingness-to-pay threshold.

2025-05-01·Diabetes Therapy

Long- and Short-Term Cost-Effectiveness of Once-Weekly Semaglutide versus Dulaglutide for the Treatment of Type 2 Diabetes in China: A Hypothetical Modeling Exercise

Article

作者: Li, Yijun ; Zou, Huimin ; Ni, Qi ; Mu, Yiming ; Chen, Xianwen ; Ung, Carolina Oi Lam ; Zhang, Hao ; Hu, Ying ; Hu, Hao ; Shen, Yang

INTRODUCTION:

This study aimed to evaluate the long- and short-term cost-effectiveness of once-weekly semaglutide versus dulaglutide for treating patients with type 2 diabetes uncontrolled with metformin after the renewal of China's national reimbursement drug list.

METHODS:

This analysis was conducted using the Institute of Health Economics Diabetes Cohort Model (IHE-DCM) to evaluate the long-term health and economic outcomes of semaglutide 0.5 mg, 1.0 mg, and dulaglutide 1.5 mg. It was performed from the perspective of the Chinese healthcare systems over a 40-year time horizon, with an annual discount rate of 5%. Baseline cohort characteristics and treatment effects were sourced from the head-to-head clinical trial SUSTAIN 7, which compared the efficacy and safety of semaglutide and dulaglutide. The analysis included direct medical costs regarding antidiabetic treatment and complication treatment. The long-term cost-effectiveness analysis used quality-adjusted life years (QALYs) as the primary health outcome. The robustness of the results was evaluated through one-way sensitivity analyses and probabilistic sensitivity analyses. The short-term cost-effectiveness analysis, focusing on the proportion of patients achieving clinical targets as the health outcome, compared the control costs of successfully treating a patient to meet clinical treatment goals between semaglutide 0.5 mg, 1.0 mg, and dulaglutide 1.5 mg over a 40-week study period.

RESULTS:

Compared with dulaglutide 1.5 mg, once-weekly semaglutide 0.5 mg demonstrated an improvement of 0.08 QALYs and a reduction in total direct medical costs of 5476 Chinese yuan (CNY); Once-weekly semaglutide 1.0 mg showed an increase of 0.19 QALYs, and a decrease in total direct medical costs of 6711 CNY. Sensitivity analyses confirmed the robustness of these results. In the short-term cost-of-control study, once-weekly semaglutide 0.5 mg demonstrated lower treatment costs for all targets: the costs of control for dulaglutide 1.5 mg were 1.2-2.1 times as much as that of semaglutide 0.5 mg once weekly. Semaglutide 1.0 mg achieved similar treatment costs for the good glycemic control goal (HbA_1c < 7%) to dulaglutide 1.5 mg. However, when looking at tight glycemic control, weight management targets, and composite targets relating to weight loss, once-weekly semaglutide 1.0 mg showed lower treatment costs compared to dulaglutide 1.5 mg to bring at least one patient to achieve these targets.

CONCLUSIONS:

Compared to dulaglutide 1.5 mg, once-weekly semaglutide remains cost-effective for treating type 2 diabetes uncontrolled on metformin in China under the new negotiation price. However, limitations exist, including the reliance on SUSTAIN-7 data and the lack of specific utility data for the Chinese population.

2025-04-17·Cardiology in Review

Efficacy of Semaglutide and Other GLP-1 Agonists in Patients with Heart Failure With Preserved Ejection Fraction and Obesity: A Systemic Review and Meta-Analysis.

Article

作者: Shembesh, Rana H ; Kara, Arwi Omar ; Elhadi, Muhammed ; Arhaym, Esraa ; Beshr, Mohammed S ; Salama, Abdelaziz H ; Abuajamieh, Maram

Semaglutide, a novel drug, has shown potential benefits for heart failure with preserved ejection fraction (HFpEF) and obesity in early trials. This study aims to evaluate the efficacy and safety of semaglutide and other glucagon-like peptide-1 (GLP-1) agonists in HFpEF patients with obesity. A comprehensive electronic search was conducted on October 18, 2024, using PubMed, Scopus, Web of Science, Embase, and Cochrane. Eligible studies included those comparing semaglutide or other GLP-1 agonists to placebo in this patient population. Primary outcomes included changes in 6-minute walking distance, Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), body weight, and secondary endpoints. Of 1116 studies, 4 met the inclusion criteria, comprising 2194 patients. GLP-1 agonists demonstrated a mean difference (MD) in 6-minute walking distance of 17.14 m [95% confidence interval (CI): 11.92-22.35, P < 0.001] and an MD in KCCQ-CSS of 7.3 (95% CI: 5.09-9.51, P < 0.001), indicating significant improvements in physical function and quality of life. Weight loss was substantial, with an MD of -7.19 kg (95% CI: -11.28 to -3.09, P = 0.001), alongside reduced inflammatory markers (C-reactive protein MD: -30.18, 95% CI: -38.16 to -22.2, P < 0.001). Hospitalizations or urgent care visits for heart failure were reduced (OR: 0.32, 95% CI: 0.15-0.66, P < 0.001). However, gastrointestinal adverse events leading to discontinuation were higher in the other GLP-1 agonists group (OR: 2.996, 95% CI: 1.683-5.331, P < 0.001). In HFpEF patients with obesity, GLP-1 agonists significantly improved symptoms, quality of life, physical function, and weight loss while reducing heart failure-related hospitalizations, though with increased gastrointestinal side effects.

项与司美格鲁肽（中山万汉）相关的新闻（医药）

2025-05-14

·BioPharmaDive

Novo to work with Septerna in hunt for oral obesity drugs

Dive Brief:Novo Nordisk on Wednesday said it will collaborate with biotechnology startup Septerna to hunt new obesity drug prospects, agreeing to pay the California drugmaker more than $200 million in upfront and near-term fees.Septerna and Novo will initially prioritize four experimental programs aimed at drug targets like GLP-1, GIP or glucagon receptors. The companies will use Septernas technology for crafting drugs that can work on so-called G protein-coupled receptors, or GPCRs.The deal is the latest step in Novos efforts to develop a pill that can complement or replace its blockbuster injectable medicine Wegovy for treating obesity. The company recently submitted an oral version of semaglutide Wegovys main ingredient for U.S. approval.Dive Insight:Novo is racing against rival Eli Lilly to develop and market an oral obesity pill. In April, Lilly read out promising data from a Phase 3 trial of its treatment orforglipron in a study of people with diabetes.Establishing a convenient alternative to injectable therapies could be a lucrative opportunity in a market investors and analysts expect to exceed $100 billion in annual sales by next decade.By turning to Septerna, a clinical-stage company testing a drug in hypoparathyroidism, Novo is focusing on GPCRs, a family of proteins thats targeted by a large proportion of approved medicines. GLP-1, GIP and glucagon receptors are GPCRs.Septerna has demonstrated strong capabilities in GPCR drug discovery, and we are excited about the opportunity to develop oral small molecule medicines directed at multiple targets, Novos Chief Scientific Officer Marcus Schindler said in a statement.Both companies will collaborate on R&D from program discovery stages through to candidate selection. Novo will take over development for preclinical testing ahead of an application to trial a new drug. Septerna could receive as much as $2.2 billion in additional payments from Novo if it hits certain R&D and commercial milestones.Under the agreement, Septerna also has the right to opt into global profit-sharing for one of the drugs in place of future milestone and royalty payments for that program.Novo will cover all development costs for the experimental medicines.The deal is the latest research collaboration Novo has struck to gain follow-up prospects to semaglutide. Among its investments are a triple agonist shot from a Chinese drugmaker and a long-acting GLP-1 shot its advancing with Ascendis Pharma.While semaglutide continues to bring in billions of dollars for Novo, the drugmaker recently had to cut sales forecasts as competition from compounded versions hurt its growth. '

临床3期引进/卖出上市批准

2025-05-08

·药智网

司美格鲁肽有望成为覆盖多系统疾病的 “超级药物”

司美格鲁肽（Semaglutide）作为全球最畅销的GLP-1受体激动剂之一，近年来在研发领域持续突破，以下是截至2025.4.10的最新进展（向《豆包》提问，得到的调研结果）：1.适应症拓展：多系统疾病慢性肾病（CKD）2025年1月，美国FDA批准司美格鲁肽（Ozempic）用于降低2型糖尿病合并慢性肾病患者的心血管死亡风险及肾功能恶化风险。这一适应症的获批基于III期FLOW试验的中期数据，显示司美格鲁肽显著降低患者心血管事件和终末期肾病风险，且在不同肾功能阶段（eGFR≥15 ml/min/1.73m²）均有效。非酒精性脂肪性肝炎（NASH）2024年11月公布的III期ESSENCE试验结果显示，司美格鲁肽2.4mg治疗代谢功能障碍相关脂肪性肝炎（MASH）患者72周后，37%的患者肝纤维化改善且无脂肪性肝炎恶化，显著优于安慰剂组的22.5%。诺和诺德计划于2025年上半年向欧美提交监管申请，有望成为首个获批治疗NASH的GLP-1药物。心血管疾病二级预防2025年美国心脏病学会（ACC）公布的SOUL试验结果显示，口服司美格鲁肽（14mg/日）使2型糖尿病合并动脉粥样硬化性心血管疾病或慢性肾病患者的主要不良心血管事件（MACE）风险降低14%，且安全性可控。这是首个证实口服GLP-1药物心血管获益的大型试验，为无法接受注射的患者提供了新选择。2.剂型创新：口服制剂的临床突破口服司美格鲁肽（Rybelsus）的减重适应症2024年8月，诺和诺德宣布口服司美格鲁肽25mg的III期OASIS 4研究成功，治疗72周后患者体重降幅达13.6%（安慰剂组2.2%），且安全性与注射剂一致。此前，口服50mg剂型已在OASIS 1研究中实现17.4%的体重下降。若获批，口服制剂将进一步扩大司美格鲁肽在肥胖症领域的应用。给药方式优化诺和诺德正在开发下一代RELiZORB装置，通过优化配方兼容性提高口服生物利用度，预计2025年推出。此外，长效制剂（如每月一次注射）的研发也在推进中。3.国产竞争与产能扩张国内药企加速跟进翰宇药业：其司美格鲁肽注射液（HY310）针对肥胖适应症的III期临床于2024年9月启动，直接对标原研药，预计2025年上半年完成数据揭盲。中国生物制药：司美格鲁肽注射液（2型糖尿病适应症）III期临床于2024年1月启动，计划入组492例患者。华东医药、联邦制药：同类产品均处于III期阶段，预计2025年提交上市申请。产能瓶颈缓解诺和诺德通过控股股东Novo Holdings以165亿美元收购CDMO巨头Catalent，获得其3个灌装-成品基地，大幅提升司美格鲁肽产能，以应对全球供不应求的局面。4.联合疗法与长期安全性与SGLT-2抑制剂联用多项研究显示，司美格鲁肽与SGLT-2抑制剂（如达格列净）联合使用可进一步降低血糖、减轻体重，并增强心血管保护作用。2025年中国糖尿病防治指南已将GLP-1RA/SGLT-2抑制剂列为合并心血管疾病或慢性肾病患者的一线治疗。长期安全性数据非糖尿病肥胖患者：2024年《美国心脏病学会杂志》（JACC）发表的荟萃分析显示，司美格鲁肽治疗68周后，患者体重平均下降12.3kg，且胃肠道副作用多为短暂性。儿童肥胖：2023年试验显示，司美格鲁肽使45%的青少年体重降至肥胖标准以下，但需结合生活方式干预。5.潜在新适应症探索5阿尔茨海默病尽管目前无直接数据，但GLP-1受体在中枢神经系统的表达提示司美格鲁肽可能改善认知功能。诺和诺德已启动II期试验（NCT05892704），探索其对早期阿尔茨海默病的疗效。儿科适应症司美格鲁肽在儿童肥胖症中的III期试验（NCT05505303）正在进行，预计2025年公布数据，可能成为首个获批用于青少年的GLP-1药物。6.结语司美格鲁肽的研发已从糖尿病和肥胖症扩展到心血管疾病、慢性肾病、NASH等领域，并通过口服制剂和产能扩张巩固市场地位。国产药物的快速跟进和联合疗法的探索进一步推动了这一药物的临床价值。未来，随着更多适应症的获批和剂型创新，司美格鲁肽有望成为覆盖多系统疾病的“超级药物”。注：以上内容仅为AI结合大数据分析推测，不作为任何决策使用。声明：本内容仅用作医药行业信息传播，不代表药智网立场。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

临床3期临床结果临床成功并购

2025-05-02

·FiercePharma

Madrigal's Rezdiffra, the first-ever MASH drug, beats sales projections for 4 quarters in a row

Madrigal Pharmaceuticals’ fatty liver disease drug Rezdiffra generated $137 million in sales during the first quarter of 2025, well above analysts’ consensus expectation of $112 million. Since its historic FDA approval in March 2024 as the first medication for the treatment of the prevalent liver disease metabolic dysfunction-associated steatohepatitis (MASH), Madrigal Pharmaceuticals’ Rezdiffra has handily beat Wall Street’s sales projections for the fourth straight quarter.On a roll, Rezdiffra generated $137 million in sales during the first quarter of 2025, well above analysts’ average expectation of $112 million. The haul also marked a sequential increase from the fourth quarter’s $103 million, which also beat consensus, bringing the drug’s sales in the first 12 months on the market to $317 million.“By any measure, this is an exceptional launch,” Madrigal CEO Bill Sibold said on an investor call Thursday.“Importantly, the Rezdiffra launch continues to be driven by strong underlying patient demand,” Leerink Partners analysts wrote in a Thursday note.As of the end of March, more than 17,000 MASH patients were actively taking Rezdiffra, compared with more than 11,800 at year-end 2024, according to Madrigal. Rezdiffra’s speed of adding new patients matches that from other top-tier specialty launches, Sibold said.The launch is still at an early stage, as Madrigal is targeting 315,000 patients who fall under Rezdiffra’s FDA-approved label and are currently treated by the company’s target prescribers. Among the 6,000 top MASH prescribers targeted by Madrigal, 70% have prescribed Rezdiffra, Sibold said. Before Rezdiffra’s approval, investors were worried that the FDA would require patients to undergo a liver biopsy to determine treatment eligibility. Now that the drug’s label doesn’t require that test, a potential restriction by payers has become a new investor concern.A key opinion leader in the MASH field—who leads the fatty liver clinic at an academic center in California that takes care of about 3,000 MASH patients—recently told Leerink that he has not encountered a single payer requiring liver biopsy before granting access to Rezdiffra.The expert indicated that 90% of his patients have remained on Rezdiffra after a year of treatment, with a small percentage of discontinuations related to tolerability or lack of treatment response, according to a Leerink note on Thursday.In what Sibold described as a standard move for medicines, payers may require reauthorization of Rezdiffra after a year of treatment based on a patient’s performance. The company doesn’t see that as an issue, he said, as physicians’ feedback so far suggests the drug's efficacy has exceeded expectations.“Physicians and patients continue to highlight meaningful improvements they see on the efficacy measures that matter most to patients such as liver stiffness, liver fat, liver enzymes, LDL and triglycerides,” Sibold said on the call.Competition may be coming, though, potentially first in the form of Novo Nordisk’s formidable GLP-1 semaglutide later this year.Novo is targeting a market that’s “multiples” the size of Madrigal’s target population of 315,000 patients, Sibold noted. Given that Rezdiffra has only penetrated 5% of its own target population, Madrigal still sees “years of growth” ahead, he said.About 25% of Rezdiffra takers are already on a GLP-1 product, Sibold noted, suggesting that there’s still a need for other MASH treatments despite the GLP-1 drugs having been around for more than a decade, albeit not specifically for MASH.Semaglutide is “only going to accelerate diagnosis and add to that” target, Sibold added, suggesting Novo will expand the market to the benefit of Madrigal as well. Putting potential geographic market expansion in its own hands, Madrigal is expecting a regulatory opinion from the European Medicines Agency and subsequent EU market authorization in mid-2025. The company plans to launch first in Germany in the second half of the year.While Rezdiffra is currently approved for stage F2 and F3 non-cirrhotic MASH, also known as nonalcoholic steatohepatitis (NASH), Madrigal is also aiming to unlock the F4 cirrhotic population.The company will present detailed two-year data from the compensated MASH cirrhosis arm of the phase 3 Maestro-NAFLD-1 trial next week at the European Association for the Study of the Liver Congress. Outcomes data from the large Maestro-NASH Outcomes trial in compensated cirrhosis are expected in 2027.The expansion to F4 cirrhosis is “a key pillar of our long-term NASH leadership strategy,” Sibold said, noting that the indication could double Rezdiffra’s market opportunity.