Oral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes

作者：Rodica Pop-Busui, S. Munkgaard Rasmussen, John E. Deanfield, John B. Buse, N Marx, Sharon L. Mulvagh, Silvio E. Inzucchi, Johannes F E Mann, Scott S. Emerson, Neil Poulter, Mads D. M. Engelmann, G. Kees Hovingh, Katrine Tanggaard, Andreas L. Birkenfeld, Kim A. Connelly, M. Haluzík, Matthew A. Cavender, Monika Kellerer, Pardeep S. Jhund, Søren Gregersen, Olav Wendelboe Nielsen, Bouchra Lamia, Darren K. McGuire, SOUL Study Group, P Schelde, Aslam Amod, Borys Mankovsky, Cyrus Desouza, JUAN J. GORGOJO-MARTINEZ, Rosario Arechavaleta, Shih‐Te Tu, José Francisco, Robinson Sánchez García, Francis Chun Chung Chow, Hirotaka Watada, Kun Ho Yoon, Federico Pérez Manghi, José M Pozzi, Alberto Lorenzatti, Virginia Esther Visco, Daniel Piskorz, Lucrecia Nardone, Mariano I. Chahin, Miguel Bustamante Labarta, Cecilia Luquez, Ignacio J. MacKinnon, Thomas Pieber, R. Prager, Evelyn Fließer-Görzer, Christoph Ebenbichler, Peter Fasching, Chantal Mathieu, Christophe De Block, Francis Duyck, Ellen Heyns, Bruno Lapauw, Luiz A. A. Turatti, DENISE FRANCO, Rosângela Rogisnki Réa, Hugo Lisboa, João Eduardo Nunes Salles, José F. K. Saraiva, Alberto G. T. Fonseca, Maria H. Vidotti, Silmara Oliveira Leite, Naresh Aggarwal, Harpreet Bajaj, Robert Schlosser, Luis Noronha, SUE PEDERSEN, Guy Tellier, John Weisnagel, Sorin Beca, Hani Alasaad, Zubin Punthakee, John G. B. Mancini, Richard Tytus, Thomas Ransom, Mansoor Husain, Michael Tsoukas, Linong Ji, Jun Liu, Guoyue Yuan, Xinhua Ye, XIAOLIN DONG, Fang Bian, A. Angelo Cadena Bonfanti, Ivan D. Hernandez Erazo, Eder A. Hernández Ruiz, Juan E. Gómez Mesa, Silvija Canecki-Varzic, Jelena Vučak Lončar, Vesna Simegi-Djekic, Tina Tičinović Kurir, Srećko Tušek, Dario Rahelić, Srečko Marušić, Ivan Kruljac, Daniela Fabris Vitković, Martina Oznerova, Jan Vrkoc, Barbora Doležalová, Z Jankovec, Jindřich Olšovský, Jitka Zemanova, Pavlina Kyselova, Alena Šmahelová, Ane Mette Z. Olsen, Dennis Mikkelsen, Kenneth Egstrup, Ulrik Pedersen-Bjergaard, Louis Potier, S Borot, Bénédicte Gaborit, Arnaud Monier, Alain Pradignac, Bruno Verges, Alice Larroumet, Jean-Francois Thuan, J Lüdemann, Michael Esser, Gerd Kahrmann, Hans-Peter Kempe, Thorsten Koch, Christoph Axthelm, Björn Paschen, Ludger Rose, Thomas Schaum, Jörg Schulze, Andreas Staudenmeyer, Veronika Wenzl-Bauer, Ronald C. W. Ma, Nihal Thomas, V. Mohan, Vijay Sekhar Reddy, Paturi V. Rao, Rakesh Sahay, Jasminder Singh, Anupam Prakash, Nikhil Tandon, Tiven Marwah, Tirthankar Chaudhury, Sujoy Ghosh, Alok Kumar Kanungo, Naveen Mittal, Jubbin J. Jacob, Manoj Chadha, Nikhil M. Bhagwat, Sunil M. Jain, N. K. Thulaseedharan, Gopalakrishnan Girithara, A. Desai, S. K. Sharma, Sreenivasa Murthy, Bipin K. Sethi, Yogesh Kadam, Jothydev Kesavadev, Bipin V. Daxini, Rajeev Chawla, Unnikrishnan Gopalakrishnan, Manash P. Baruah, Sudhakar P. Reddy, K. M. Suryanarayana, Kiran P. Singh, Banshi Saboo, Genya Aharon-Hananel, Irit Hochberg, Yael Sofer, Amir Tirosh, Ilan Shimon, Victor Vishlitzky, Amir Bashkin, Anat Tsur, Michael Shechter, Francesco Andreozzi, Emanuela Setola, Agostino Consoli, Roberta Lupoli, Stefano Genovese, Marianna Maranghi, Davide Lauro, Roberto Citarrella, Gian Paolo Fadini, Giuseppe Murdolo, Alberto Di Carlo, Francesco Giorgino, Silvio Buscemi, Keiichi Hanaoka, Takeshi Osonoi, Hiroshi Ohashi, Hirotaka Ezaki, Haruhito Yuki, Arihiro Kiyosue, Yoshiki Hata, Masahiro Sugawara, Hiroshi Domae, Hiroshi Iwata, Yuya Nishida, Masaki Igarashi, Susumu Fujino, Ako Oiwa, Fumiki Oh, Atsushi Sueyoshi, Takaaki Murakami, Muhei Tanaka, Akira Idogaki, Haruhiko Onaka, Isamu Mizote, Masayuki Doi, Osamu Ebisui, Makito Tanabe, Masahiro Natsuaki, Hideaki Jinnouchi, Shuji Nakamura, Wan Mohd Izani Wan Mohamed, Norhayati Yahaya, Jeyakantha Ratnasingam, Tiong Kiam Ong, Masni Mohamad, Nor Shaffinaz Yusoff Azmi Merican, Rohana Abdul Ghani, Noor Lita Adam, Tem Lom Fam, Florence H. S. Tan, Enrique C. Morales Villegas, Guillermo González-Gálvez, Diego Espinoza Peralta, Carlos E. Medina Pech, Ana C. García Ulloa, Hugo A. Laviada Molina, R. Elizondo, José Á. Garza Ruiz, Elías A. García Cantú, Thomas van Bemmel, Harold W. de Valk, Adriaan Kooy, Louis Lieverse, S. A. N. T. Landewe-Cleuren, Klaas Hoogenberg, Daniel van Raalte, Max C.W. Jebbink, Christine Oldenburg-Ligtenberg, Evertine J. Abbink-Zandbergen, Bogdan Mihai, Carmen Nicoleta Crişan, Iuliana Filip, Mihaela M. Busegeanu, Gabriela Román, Alina C. Mot, Anca Nicoara, Veronica Anghel, Noemi N. Pletea, Mirela Suciu, Daniela Strajer, Simona Cernea, Alexei Zilov, Zhanna Kobalava, Ludmila A. Ruyatkina, Lyudmila A. Suplotova, Marina Y. Sergeeva-Kondrachenko, Maria E. Yanovskaya, Lubov Kargina, Anna Ignatyeva, Khavra Astamirova, Alsu Gafurovna Zalevskaya, Olga A. Zagrebelnaya, Е В Фролова, А. Б. Песков, Olga Mishchenko (Golinskaya), Olga Otroshchenko, Leylya Gaysina, Olesya Yurievna Shabelnikova, Tatiana V. Saprina, Tatyana Lysenko, М. А. Куницына, S. T. Zyangirova, Nebojsa Lalic, Katarina Lalić, Teodora Beljić Živković, Sasa Kikovic, Aleksandar Djukić, Milica Pešić, Dragan Dimić, Edita Stokić, Milena Mitrovic, Snežana Polovina, Miodrag Djordjević, Dalibor Sosovec, Daniel Pella, Viera Donicova, Sandra Hanackova Prasekova, Daniel Koleny, Jan Culak, Katarína Černá, Viktor Hundza, Juraj Gmitrov, J. Lacka, Radovan Plášil, Hajira B Bacus, Qasim Bhorat, P Joshi, Deepak R. Lakha, Vikash Makan, Ntobeko Ntusi, Trevenesan Padayachee, Mary Seeber, Deenadayalan Pillay, Mukesh Joshi, Leila Mayet, Joonyub Lee, SIN GON KIM, KyungWan Min, Eun Seok Kang, Woo Je Lee, Sung Hee Choi, Chang Beom Lee, Alejandro López Suárez, Miguel Ángel García Ordóñez, Antonio García Quintana, Pilar Mazón Ramos, Secundino Cigarrán, Clara Barrios, Alfonso Soto González, Esteban Jodar, Javier Delgado Lista, Cristobal Morales Portillo, Coral Montalbán Carrasco, Francisco Tinahones, Chien-Ning Huang, Szu-Tah Chen, Patinut Buranasupkajorn, Apiradee Sriwijitkamol, Supawan Buranapin, Arisara Suwanagool, Puntip Tantiwong, Apussanee Boonyavarakul, Sunun Benjachareonwong, Rattana Leelawattana, Prin Vathesatogkit, Chaicharn Deerochanawong, Yusuf A. Sonmez, Aytekin Oğuz, Omur Tabak, Mustafa Kocak, Baris Sariakcali, Fahri Bayram, Metin Güçlü, Eren Gurkan, Nur Kebapci, Abdurrahman Comlekci, Fettah Acıbucu, Süleyman Ahbab, Habib Bilen, Alina Urbanovych, Petro Kuskalo, Iryna Bondarets, Olena Petrosyan, N.V. Pashkovska, Olga Oleksyk, Igor Kaydashev, Kateryna Maliar, Galyna Myshanych, Stephen C. Bain, Duncan Black, Philip Johnston, Cuong Dang, Ketan Dhatariya, Patrick English, Ben Field, Philip Grimmer, Anthony Gunstone, Sutapa Ray, Danijela Tatović, Andrew Kernohan, Robert Lindsay, John McKnight, Adrian Park, Dipesh Patel, Sam Philip, Harpal Randeva, Thozhukat Sathyapalan, Wayne Turner, Nell Wyatt, Dale C. Allison, Vivex Awasty, Etsegenet Gossa Ayele, CHRIS BAJAJ, Matthew J. Budoff, Robert Busch, Luis Casaubon, Sushela Chaidarun, Ronald H. Chochinov, James W. Chu, Nizar Y. Daboul, Andy H. Dang, Brian G. Everhart, Justin Arambasick, Raymond I. Fink, David Fitz-Patrick, Charles M. Fogarty, Matthew P. Gilbert, David Johnson, Sathya S. Krishnasamy, Wendy S . Lane, Samer N. Nakhle, David Levenson, Philip O’Donnell, Daniel Weiss, Joseph A. Risser, Craig Wierum, Kanagaratnam Sivalingam, Dinesh Gupta, Athena Philis-Tsimikas, Richard E. Pratley, Lubna Mirza, Brian Snyder, Neda Rasouli, John Porter, Gilbert N. Ledesma, Talessa Powell, Ileana J. Tandron, Ildiko Lingvay, John C.H. Reed, Minesh Patel, Dragana Lovre, Tira Chaicha-Brom, Curtis Jantzi, Donald Brautigam, Shichun Bao, Caroline N. Mbogua, Leonard R. Zemel, Syed Hasan, Julio Rosenstock, Hien Tran, John Poremba, Claire Baker, Kevin Prier, Sapna Chilka, John M. Agaiby, Jonathan Condit, Donald C. Eagerton, David Huffman, George M. Cornett, Henry Traylor, Cynthia Brinson, Harold E. Bays, Terri Jerkins, Philip R. Nicol, Imran A. Siddiqui, Mitzie Hewitt, Adeniyi O. Odugbesan, Lillestol Michael J, James R. Thrasher, Winston H. Gandy, Nicole Pant, S Nagelberg, Kevin Cannon, Marshall W. Anderson, Anuj Bhargava, Ankur Doshi, Michael F. Jardula, Manuel Montero, Raman S. Purighalla, MARK L. WARREN, Kathleen Harris, Richard A. Jackson, Ajit S. Khaira, Luis Gonzalez-Orozco, Peter Gagianas, Kevin Pantalone, Alexander V. Murray · 发表于：JAMA Internal Medicine · 年份：2026 · DOI：10.1001/jamainternmed.2025.7774 · 被引用次数：9 · 研究领域：Diabetes Treatment and Management、Cardiovascular Function and Risk Factors、Diabetes Management and Research

Importance: Heart failure (HF) is a common complication of type 2 diabetes (T2D). Oral semaglutide reduced the risk of major adverse cardiovascular (CV) events (MACE; comprising CV death, nonfatal myocardial infarction, or nonfatal stroke) in people with T2D in the SOUL trial, but the impact on HF outcomes in these participants is unknown. Objective: To evaluate the effect of oral semaglutide on HF events, MACE, and safety among participants with or without HF at baseline. Design, Setting, and Participants: This is a secondary analysis of the double-blind, placebo-controlled, event-driven, phase 3b SOUL randomized clinical trial, which was conducted at 444 centers in 33 countries. Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline. Data were analyzed from December 2024 to August 2025. Intervention: Once-daily oral semaglutide or placebo in addition to standard of care. Main Outcomes and Measures: Prespecified composite HF outcome (time to first occurrence of HF hospitalization, urgent HF visit, or CV death). Results: Overall, 9650 participants (median [IQR] age, 66.0 [61.0-72.0] years; 2790 [28.9%] female) were randomized, with a mean (SD) follow-up of 47.5 (10.9) months. Of these participants, 2229 (23.1%) had HF history (991 [10.3%] with preserved ejection fraction, 592 [6.1%] with reduced ejection fraction, and 6...