{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:51:45Z","timestamp":1791453105732,"version":"4.3.3"},"reference-count":0,"publisher":"Bioscientifica","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n A high proportion of patients with pheochromocytomas and paragangliomas (PPGLs) show glycemic dysregulation. However, studies on the effects of anti-diabetic drugs on PPGL tumor growth are still lacking.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We evaluated the effects of glucagon-like peptide 1 receptor agonist (GLP-1RA) semaglutide, metformin and insulin on fresh patient-derived PPGL primary cultures (n=54), including 8 cluster 1 tumors and 18 cluster 2\/3 tumors (n=4 tumors with RET pathogenic variants [PVs]). We correlated the primary culture data with clinical data from 67 patients enrolled in the prospective clinical trial PROSPHEO (NCT03344016).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n We found cluster-dependent effects of semaglutide in patient primary cultures, with significant anti-tumor effects in cluster 1 PPGLs. Interestingly, we found tumor-promoting effects of high-dose semaglutide in 3 PPGLs with germline RET PVs (MEN2 syndrome), but not in a PPGL with a somatic RET PV. Metformin displayed overall anti-tumor effects while insulin showed individual tumor-promoting effects in the patient primary cultures. Consistently, clinical data confirmed larger median tumor sizes of PPGL patients receiving insulin therapy compared to patients receiving metformin\/GLP-1RA therapy or patients without anti-diabetic therapy.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Overall, we provide novel data on the effects of anti-diabetic drugs on PPGL tumor growth including significant anti-tumor effects of the GLP-1RA semaglutide in cluster 1 PPGLs, and tumor-promoting effects in patients with MEN2 syndrome. Further confirmation of our data in prospective clinical studies is required.<\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/erc-26-0283","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:14:04Z","timestamp":1791450844000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":0,"title":["Effects of a GLP-1 agonist and anti-diabetic therapies on pheochromocytoma\/paraganglioma growth"],"prefix":"10.1530","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7795-1395","authenticated-orcid":true,"given":"Katharina","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priska","family":"Stempfle","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Hamati","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessa","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich 2 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Maccio","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology, University Hospital Zurich 3 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology, University Hospital Zurich 3 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6256-5902","authenticated-orcid":true,"given":"Mercedes","family":"Robledo","sequence":"additional","affiliation":[{"name":"Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO) 4 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras 5 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Maurer","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Peischer","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Reul","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich 2 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Kuzmenko","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich 2 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich 6 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Vetter","sequence":"additional","affiliation":[{"name":"Department of Visceral and Transplantation Surgery, University Hospital Zurich 7 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Oberholzer","sequence":"additional","affiliation":[{"name":"Department of Visceral and Transplantation Surgery, University Hospital Zurich 7 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Reisch","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU 8 ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kn\u00f6sel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine, LMU 9 ,","place":["Munich, Germany"]},{"name":"Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS Centre of Excellence), LMU University Hospital 10 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias K","family":"Auer","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lottspeich","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Beuschlein","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich 2 ,","place":["Switzerland"]},{"name":"The LOOP Zurich - Medical Research Center 11 ,","place":["Switzerland"]},{"name":"ENETS Centre of Excellence Zurich, University Hospital Zurich 12 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8906-2563","authenticated-orcid":true,"given":"Constanze","family":"Hantel","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich 2 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1176-6186","authenticated-orcid":true,"given":"Ashley B","family":"Grossman","sequence":"additional","affiliation":[{"name":"Green Templeton College, University of Oxford 13 , ,","place":["Oxford, UK"]},{"name":"NET Unit, ENETS Centre of Excellence, Royal Free Hospital 14 , ,","place":["London, UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Pacak","sequence":"additional","affiliation":[{"name":"Center for Adrenal Endocrine Tumors, AKESO 15 , ,","place":["Prague 5, Czech Republic"]},{"name":"Faculty of Medicine, Palacky University 16 , ,","place":["Olomouc, Czech Republic"]},{"name":"Faculty of Medicine, 5th Department of Medicine, Commenius University 17 , ,","place":["Bratislava, Slovakia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Zitzmann","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph J","family":"Auernhammer","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]},{"name":"Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS Centre of Excellence), LMU University Hospital 10 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"N\u00f6lting","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, LMU University Hospital, LMU 1 ,","place":["Munich, Germany"]},{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich 2 ,","place":["Switzerland"]},{"name":"ENETS Centre of Excellence Zurich, University Hospital Zurich 12 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,10,7]]},"container-title":["Endocrine-Related Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.bioscientifica.com\/erc\/article-pdf\/doi\/10.1530\/ERC-26-0283\/526258\/erc-26-0283.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/erc\/article-pdf\/doi\/10.1530\/ERC-26-0283\/526258\/erc-26-0283.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:14:05Z","timestamp":1791450845000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/erc\/article\/doi\/10.1530\/ERC-26-0283\/78336\/Effects-of-a-GLP-1-agonist-and-anti-diabetic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1530\/erc-26-0283","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"ERC-26-0283"}}