Impact of Oral Semaglutide on Kidney Outcomes in People With Type 2 Diabetes: Results From the SOUL Randomized Trial

作者：Johannes F.E. Mann, Nikolaus Marx, John Deanfield, Scott S. Emerson, Silvio E. Inzucchi, Darren K. McGuire, Sharon L. Mulvagh, Rodica Pop‐Busui, Neil R Poulter, Mads D.M. Engelmann, G. Kees Hovingh, Nicolas Belmar, Thomas Idorn, Ole Kleist Jeppesen, Andreas L. Birkenfeld, Aslam Amod, Boris Mankovsky, Cyrus Desouza, Juan José Gorgojo Martínez, Rosario Arechavaleta, Shih‐Te Tu, John B. Buse, SOUL Study Group*, D. K. McGuire, John B. Buse, Johannes F.E. Mann, Nikolaus Marx, John Deanfield, S. S. Emerson, S. E. Inzucchi, Sharon L. Mulvagh, Rodica Pop‐Busui, Neil R Poulter, Mads D.M. Engelmann, G. Kees Hovingh, Per Schelde, Andreas L. Birkenfeld, Aslam Amod, Boris Mankovsky, Cyrus Desouza, Juan José Gorgojo Martínez, Rosario Arechavaleta, Shih‐Te Tu, J. Francisco, Ronald G. García, Francis C. C. Chow, Hirotaka Watada, Kun Ho Yoon, Pardeep Jhund Singh, Matthew, Federico Pérez Manghi, José M Pozzi, Alberto Lorenzatti, Valeria Visco, Daniel Piskorz, L Nardone, Mariano Chahin, M. Bustamante Labarta, Carolina Lúquez, Ignacio MacKinnon, T. Pieber, R. Prager, E. Fließer-Görzer, Christoph Ebenbichler, P. Fasching, C. Mathieu, Christophe De Block, Francis Duyck, E. Heyns, Bruno Lapauw, Luiz Alberto Andreotti Turatti, Denise Reis Franco, R. Roginski Rea, Roberta Marques Lisboa, João Eduardo Nunes Salles, José Francisco Kerr Saraiva, A. G. T. Fonseca, Márcio Vidotti, Silmara Leite, Neeru P Aggarwal, Hitasha Bajaj, Rolf Schlößer, Lúcia de Noronha, S Pedersen, Sean Peterson, Guy Tellier, John Weisnagel, Sanja Beca, Hani Al‐Asaad, Zubin Punthakee, Joseph Mancini, Richard Tytus, Thomas Ransom, Katherine Connelly, M. Husain, Michael A. Tsoukas, Linong Ji, Jie Liu, Gongsheng Yuan, X. Ye, Xinzhong Dong, Fei Bian, Andrés Ángelo, Ronald G. García, Ibeth Erazo, Emilie Ruiz, Jordi Mesa, Silvija Canecki-Varžić, Jelena Vučak Lončar, V. Simegi-Djekic, Tina Tičinović Kurir, Srecko Tusek, Dario Rahelić, Suzana Marušić, Ivan Kruljac, Danijela Fabris Vitković, Martina Oznerova, Jan Vrkoč, Barbora Doležalová, Martin Haluzı́k, Z Jankovec, Jindřich Olšovský, Jitka Zemanová, P Kyselová, Alena Šmahelová, Søren Gregersen, Anja Olsen, D. R. Mikkelsen, Kenneth Egstrup, Ulrik Pedersen‐Bjergaard, Louis Potier, Sophie Borot, Benjamin Gaborit, Anne Monier, A. Pradignac, B. Vergès, Alice Larroumet, J.F. Thuan, MONIKA KELLERER, J Lüdemann, Melissa M. Esser, Gerd Kahrmann, Hans‐Peter Kempe, Thorsten Koch, C. Axthelm, B Paschen, Laura J. Rose, Thomas Schaum, J Schulze, A. Staudenmeyer, V. Wenzl-Bauer, R. C. W., N. Thomas, Viswanathan Mohan, V. S. Reddy, Ping Rao, Rakesh Sahay, Jaipaul Singh, Anupam Prakash, N. Tandon, Tiven Marwah, Tristin Chaudhury, Saraswati Ghosh, Alok Kumar Kanungo, Naveen Mittal, Jobin John Jacob, Manoj Chadha, Manoj Chawla, Nikhil Bhagwat, Shalini Jain, N K Thulaseedharan, G. Girithara, Ankur R. Desai, Shivam Sharma, S. Murthy, Bipin Sethi, Y. Kadam, J. Kesavadev, Bipin V. Daxini, Rajesh Chawla, Unnikrishnan Gopalakrishnan, M. P. Baruah, Sekhar P. Reddy, KM Suryanarayana, Kalpana Singh, B. Saboo, Genya Aharon‐Hananel, Irit Hochberg, Yael Sofer, Amir Tirosh, Ilan Shimon, Victor Vishlitzky, Amir Bashkin, Avishai M. Tsur, Michael Shechter, Francesco Andreozzi, E. Setola, Agostino Consoli, Roberta Lupoli, S. Genovese, Marianna Maranghi, Davide Lauro, Roberto Citarrella, Gian Paolo Fadini, Giuseppe Murdolo, Antonio Di Carlo, F. Giorgino, Silvio Buscemi, Kazushige Hanaoka, Takeshi Osonoi, Hiroshi Ohashi, Haruo Ezaki, Hideo Yuki, A. Kiyosue, Y. Hata, Masashiro Sugawara, HIROSHI DOMAE, H. Iwata, Yoshio Nishida, Masahiro Igarashi, Sumiko Fujino, Ayano Oiwa, F. Oh, Atsushi Sueyoshi, T. Murakami, Masayuki Tanaka, A. Idogaki, Hiroyasu Onaka, Isamu Mizote, Masafumi Doi, Osamu Ebisui, Minoru Tanabe, Masahiro Natsuaki, Hiroshige Jinnouchi, Shuji Nakamura, Wan Mohamed, Nor Hamdan Mohamad Yahaya, Jeyakantha Ratnasingam, T.K. Ong, Masni Mohamad, Nor Shaffinaz Yusoff Azmi Merican, Rohana Abdul Ghani, N Adam, Tem Lom Fam, Fang Tan, Enrique C. Morales Villegas, Guillermo González-Gálvez, Diego Espinoza Peralta, Carlos Eduardo Medina Pech, Ana Cristina García Ulloa, Héctor Molina, R. Elizondo, José Angel Garza Ruíz, E. Cantu, Thomas van Bemmel, Harold W. de Valk, Adriaan Kooy, Louis A.G. Lieverse, S.A.N.T. Landewé-Cleuren, K. Hoogenberg, Daniël H. van Raalte, M. Jebbink, Christine P Oldenburg-Ligtenberg, E.J. Abbink-Zandbergen, Bianca-Margareta Mihai, Carmen Crișan, Irina Filip, Mihaela-Magdalena Busegeanu, Gabriela Román, Augustin C. Moţ, Alina Nicoara, Veronica Anghel, N. N. Pletea, Maria Suciu, D. Strajer, Simona Cernea, Алексей Вадимович Зилов, Ж. Д. Кобалава, L. A. Ruyatkina, Л. А. Суплотова, M. Sergeeva-Kondrachenko, M. E. Yanovskaya, L. Kargina, A.V. Ignatyeva, K. Astamirova, Alsu Gafurovna Zalevskaya, Olga A. Zagrebelnaya, Е. В. Фролова, А. Б. Песков, O. Ya. Mishchenko, O. Otroshchenko, Leyla Gaysina, O. Y. Shabelnikova, T. V. Saprina, Т. А. Лысенко, М. А. Куницына, S. T. Zyangirova, Nebojša Lalić, Katarina Lalić, Teodora Beljić Živković, Sasa Kikovic, Aleksandar Djukić, M. Pesic, Dragan Dimić, Edita Stokić, Milena Mitrović, Snežana Polovina, Miladin Djordjevic, Dalibor Sosovec, Daniel Pella, Viera Doničová, S. Hanackova Prasekova, Daniel Koleny, Jan Culak, K. Cerna, V. Hundza, Juraj Gmitrov, J. Lacka, Radovan Plášil, Hajira B Bacus, Qasim Bhorat, Pradeep Joshi, Deepak Lakha, V. Makan, Ntobeko Ntusi, Trevenesan Padayachee, Mary Seeber, Deenan Pillay, M. Joshi, L. Mayet, Jong Eun Lee, S. G. Kim, Kyong Wan Min, Eun Seok Kang, Wookjin Lee, Sun-Ja Choi, Chul‐min Lee, Ana López Suárez, M. Araujo Ordoñez, A. García Quintana, P. Mazón Ramos, S. Cigarrán, Carlos H. Barrios, A. Soto González, Esteban Jódar, Javier Delgado‐Lista, C. Morales Portillo, C. Montalbán Carrasco, Francisco J. Tinahones, S. Cigarrán, C.-N. Huang, Shao-Chia Chen, P. Buranasupkajorn, Apiradee Sriwijitkamol, Supawan Buranapin, Arisara Suwanagool, Puntip Tantiwong, Apussanee Boonyavarakul, Sunun Benjachareonwong, Rattana Leelawattana, Prin Vathesatogkit, Chaicharn Deerochanawong, Alper Sönmez, Aytekin Oğuz, Ömür Tabak, Mehmet Koçak, Barış Sarıakçalı, Fahrı Bayram, M. Guclu, Eren Gürkan, Nur Kebapçı, A. Comlekci, Fettah Acıbucu, Süleyman Ahbab, Habib Bilen, Alina Urbanovych, Petro Kuskalo -, Iryna Bondarets, Olena Petrosyan, N.V. Pashkovska, О.T. Oleksyk, І. P. Kaydashev, К. Ю. Маляр, Galyna Myshanych, Stephen C. Bain, D. Black, P. Johnston, Cuong Dang, K. Dhatariya, Patrick English, B Field, P. Grimmer, Anthony Gunstone, Subir Ray, Danijela Tatović, Andrew Kernohan, Robert S. Lindsay, John McKnight, A. Park, Dipesh Patel, Sam Philip, Harpal Randeva, Thozhukat Sathyapalan, Wayman E. Turner, Naomi A. Wyatt, D. C. Allison, Vivek Awasty, Esubalew Tesfahun Ayele, Chandrajit Bajaj, M. J. Budoff, Robert S. Busch, Leanne K. Casaubon, Sushela Chaidarun, R. H. Chochinov, Jaeryang Chu, Nizar Daboul, Amit Dang, Brian G. Everhart, J. Arambasick, R. I. Fink, David Fitzpatrick, Charles Fogarty, Michael Gilbert, Daniel M. Johnson, SENTHILKUMAR KRISHNASAMY, W S Lane, Samer Nakhle, D Levenson, Patrick O’Donnell, D. Weiss, Joseph Risser, Carl Wierum, K. Sivalingam, Daksh Sanjay Gupta, A. Philis-Tsimikas, R. E. Pratley, Lubna Mirza, Brian D. Snyder, N. Rasouli, Julie A. Porter, Gilbert Ledesma, T. D. Powell, I. J. Tandron, I. Lingvay, Joseph Reed, Mayur B. Patel, Dragana Lovre, Tira Chaicha-Brom, Curtis Jantzi, D. H. Brautigam, Shichun Bao, C. N. Mbogua, Lawrence Zemel, Syed Shahzad Hasan, J. Rosenstock, Hoang Minh Tran, John A. Poremba, C. Baker, Kim Prier, S Chilka, John Agaiby, J. Condit, Donald Eagerton, Derek M. Huffman, George Mitchell Cornett, Henry Traylor, Cynthia Brinson, Harold Bays, Terri Jerkins, P. Nicol, Ishratullah Siddiqui, Mark Hewitt, A. Ola Odugbesan, Michael Lillestol, James Thrasher, Winston Gandy, Nicole Pant, S Nagelberg, K. Cannon, M. Anderson, Anuj Bhargava, Ankur Doshi, Michael Jardula, M. Montero, Raman Purighalla, Mark Warren, Kathleen Mullan Harris, R. A. JACKSON, Ajit S Khaira, B. L. Gonzalez-Orozco, Peter Gagianas, Kevin M. Pantalone, Alexander V. Murray · 发表于：Diabetes Care · 年份：2025 · DOI：10.2337/dc25-1080 · 被引用次数：8 · 研究领域：Diabetes Treatment and Management、Chronic Kidney Disease and Diabetes、Renal Transplantation Outcomes and Treatments

OBJECTIVE: To examine the effects of oral semaglutide on kidney outcomes in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: SOUL (NCT03914326), a double-blind randomized controlled trial, compared oral semaglutide with placebo in people with T2D, ASCVD, and/or CKD, showing a 14% reduction in risk of major adverse cardiovascular (CV) events. Prespecified kidney outcomes included a five-point composite (≥50% decrease in estimated glomerular filtration rate [eGFR], persistent eGFR <15 mL/min/1.73 m2, initiation of chronic kidney replacement therapy, or death from kidney or CV causes); a four-point composite (excluding CV death); and eGFR decline. Prespecified subgroups were also assessed, including those with eGFR <60 mL/min/1.73 m2 at baseline. RESULTS: Among 9,650 participants, mean eGFR was 73.8 mL/min/1.73 m2, and follow-up was 47.5 months. The five-point outcome occurred in 403 (8.4%) and 435 (9.0%) participants taking oral semaglutide versus placebo, respectively (hazard ratio [HR] 0.91; 95% CI 0.80, 1.05; P = 0.19). The four-point outcome occurred in 112 (2.3%) and 129 (2.7%) participants, respectively (HR 0.86; 95% CI 0.66, 1.10; P = 0.22). Mean annual eGFR decline was less with oral semaglutide than placebo (-1.67 vs. -2.06 mL/min/1.73 m2; estimated treatment difference 0.40 [95% CI 0.27, 0.53; P < 0.0001). These effects were similar across most subgroups, including th...