[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-439881-105":3,"detail-sidebar-cat-0-en-105":85,"doc-detail-439881-en":134},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":78,"head_meta":80,"extra_data":82,"updated_unix":84},105,"en","a-new-era-in-oral-treatment-for-acromegaly-with-the-fda-approved-drug-paltusotine-letter-to-the-editor","A new era in oral treatment for acromegaly with the FDA-approved drug paltusotine - Letter to the Editor","","Letter to the Editor describing the U.S. FDA approval of paltusotine on 26 September 2025 as the first once-daily oral therapy for adults with acromegaly when surgery is ineffective or not an option. The letter explains acromegaly’s hormonal basis, contrasts oral paltusotine with long-term injectable somatostatin analogs, and outlines its SSTR2 selective, nonpeptide mechanism. Clinical data are summarized, including tolerability, dosing effects on GH and IGF-1, and the absence of unexpected safety signals in the PATHFNDR-2 trial, while noting the need for further long-term research.",{"@graph":14,"@context":77},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/a-new-era-in-oral-treatment-for-acromegaly-with-the-fda-approved-drug-paltusotine-letter-to-the-editor/439881/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/a-new-era-in-oral-treatment-for-acromegaly-with-the-fda-approved-drug-paltusotine-letter-to-the-editor/439881.png","ImageObject",300,407,{"name":42,"@type":43},"Dipper","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69,73],{"name":60,"@type":61,"acceptedAnswer":62},"What did the FDA approve for acromegaly, and when?","Question",{"text":63,"@type":64},"The FDA approved paltusotine on 26 September 2025 as the first once-daily oral treatment for adults with acromegaly who have ineffective surgery or surgery is not an option.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Why is an oral therapy considered an important improvement over injectables for acromegaly?",{"text":68,"@type":64},"The letter links oral convenience to improved compliance and reduced treatment burden, addressing limitations of lifetime injectable somatostatin analog use and related discomfort.",{"name":70,"@type":61,"acceptedAnswer":71},"How does paltusotine work at the molecular level?",{"text":72,"@type":64},"Paltusotine selectively binds SSTR2, activating Gi protein-coupled signaling and inhibiting adenylyl cyclase to reduce intracellular cAMP, suppressing GH and IGF-1 secretion.",{"name":74,"@type":61,"acceptedAnswer":75},"What safety and tolerability findings are highlighted?",{"text":76,"@type":64},"In the PATHFNDR-2 trial, paltusotine was well tolerated with no significant unexpected safety signals; the most frequent adverse effects were headache, nausea, and exhaustion, described as mild and typical.","https://schema.org",{"og:url":32,"og:type":79,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":81,"canonical":32},"index,follow",{"doc_id":83,"site_id":7},439881,1790768073,{"code":4,"msg":86,"data":87},"success",[88,92,96,100,105,110,114,119,123,126,130],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Exam",70,"exam",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},5,"Comic",60,"comic",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},6,"Technology",50,"technology",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},7,40,"healthcare",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":121,"slug":122},"Religion & Spirituality",20,"religion-spirituality",{"id":121,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":121,"slug":125},"World Cup","world-cup",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":127,"slug":129},10,"Lifestyle","lifestyle",{"id":131,"doc_module":4,"doc_module_name":25,"category_name":132,"show_sort_weight":101,"slug":133},19,"General","general",{"code":4,"msg":86,"data":135},{"doc_id":83,"user_id":136,"nickname":42,"user_avatar":137,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":26,"language":143,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":144,"faqs":145,"seo_title":146,"seo_description":12,"update_tm":147,"read_time":101,"preview_page_count":4},1374404997633,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Letter to the Editor  \nA new era in oral treatment for acromegaly with the FDA-approved drug paltusotine  \nSuhail Ahmed, MBBSa , Hayat Asghar, MBBSa , Muddassir Khalid, MBBSb ,*  \nDear Editor,  \nPaltusotine was approved by the U.S. Food and Drug Administration (FDA) on 26 September 2025, as the first oncedaily oral treatment for acromegaly in adults for whom surgery was either ineffective or not an option[1] .This approval marks an important milestone in the management of acromegaly, a chronic hormonal disorder requiring long-term medical therapy. A benign pituitary adenoma typically causes acromegaly, a rare endocrine disorder that results in excessive growth hormone (GH) secretion and elevated insulin-like growth factor-1 (IGF-1) levels. Paltusotine’s approval represents a significant step forward in the long-term medical treatment of acromegaly, particularly for patients switching from injectable somatostatin analogs to oral therapy. Even though injectable somatostatin analogs are effective, the need for more convenient oral therapies has been brought to light by their lifetime administration requirements and related discomfort. Injectable somatostatin analogs like octreotide or lanreotide have long been used to treat acromegaly, which is characterized by elevated IGF-1 and chronic GH hypersecretion. It is anticipated that the creation of a successful oral substitute will significantly increase patient compliance, lessen the burden of treatment, and improve quality of life. A nonpeptide selective somatostatin receptor-2 agonist called paltusotine is being developed as a once-daily oral medication to treat acromegaly. In patients with acromegaly, replacing injected somatostatin receptor ligands (SRLs) with oncedaily oral paltusotine was well tolerated and maintained both biochemical and symptom control[2] .  \nPaltusotine’s therapeutic benefit stems from both its distinct molecular mechanism and oral formulation. By selectively binding to the somatostatin receptor subtype 2 (SSTR2), paltusotine, an oral small-molecule agonist, activates Gi protein-coupled signaling and inhibits adenylyl cyclase, thereby lowering intracellular cAMP levels. GH and IGF-1 secretion are suppressed by  \naDepartment of Medicine, Liaquat University of Medical & Health Sciences (LUMHS), Jamshoro and Pakistan and bDepartment of Medicine, Nishtar Medical University, Multan, Pakistan  \nSponsorships or competing interests that may be relevant to content are disclosed at the end of this article.  \n*Corresponding author. Address: Department of Medicine, Nishtar Medical University, Nishtar Road, Multan 60000, Pakistan. Tel.: +92 3330333544.  \n[E-mail: dr.muddassirkhalid@gmail.com](E-mail: dr.muddassirkhalid@gmail.com) (M. Khalid).  \nCopyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.  \nAnnals of Medicine & Surgery (2026) 88:1068–1069  \nReceived 11 November 2025; Accepted 13 November 2025  \nPublished online 3 December 2025  \n[http://dx.doi.org/10.1097/MS9.0000000000004426](http://dx.doi.org/10.1097/MS9.0000000000004426)  \nthis action. According to cryo-EM research, paltusotine produces a unique SSTR2 conformation that leads to biased signaling and enhanced receptor selectivity, offering a targeted and efficient treatment for neuroendocrine tumors and acromegaly. Its clinical superiority is further elucidated by comprehending the pharmacologic differences between this novel nonpeptide agent and conventional peptide analogs. Although both paltusotine and octreotide work via SSTR2, their mechanisms vary in terms of selectivity and efficiency. Compared to octreotide, paltusotine exhibits a more effective and selective mechanism. While octreotide, a first-generation peptide, has variable cell surface expression and limite","cbCaidWz7JyoXLLV","https://ap.wps.com/l/cbCaidWz7JyoXLLV","pdf",162651,"English","# Letter to the Editor: A new era in oral treatment for acromegaly with the FDA-approved drug paltusotine\n## FDA approval and clinical rationale\n## Mechanism of action and pharmacology\n## Efficacy, tolerability, and safety profile\n## Compliance, ethics, funding, and declarations","[{\"question\":\"What did the FDA approve for acromegaly, and when?\",\"answer\":\"The FDA approved paltusotine on 26 September 2025 as the first once-daily oral treatment for adults with acromegaly who have ineffective surgery or surgery is not an option.\"},{\"question\":\"Why is an oral therapy considered an important improvement over injectables for acromegaly?\",\"answer\":\"The letter links oral convenience to improved compliance and reduced treatment burden, addressing limitations of lifetime injectable somatostatin analog use and related discomfort.\"},{\"question\":\"How does paltusotine work at the molecular level?\",\"answer\":\"Paltusotine selectively binds SSTR2, activating Gi protein-coupled signaling and inhibiting adenylyl cyclase to reduce intracellular cAMP, suppressing GH and IGF-1 secretion.\"},{\"question\":\"What safety and tolerability findings are highlighted?\",\"answer\":\"In the PATHFNDR-2 trial, paltusotine was well tolerated with no significant unexpected safety signals; the most frequent adverse effects were headache, nausea, and exhaustion, described as mild and typical.\"}]","A new era in oral treatment for acromegaly with the FDA-approved drug paltusotine - Letter to the Editor | PDF",1790690467]