Effects of Semaglutide With or Without Concomitant Mineralocorticoid Receptor Antagonist Use in Participants With Type 2 Diabetes and Chronic Kidney Disease: A FLOW Trial Prespecified Secondary Analysis

作者：Peter Rossing, George L. Bakris, Vlado Perkovic, Richard E. Pratley, Katherine R. Tuttle, Kenneth W. Mahaffey, Thomas Idorn, Nicolas Belmar, Heidrun Bosch‐Traberg, Søren Rasmussen, Robert S. Busch, Roland E. Schmieder, Pieter Gillard, Johannes F. E. Mann, FLOW Investigator Group, Andrea Da Porto, A. Oviedo, Alicia Elbert, Elizabeth Gelersztein, Alejandro Chertkoff, A. Wassermann, Miguel Ángel Quevedo, R. J. MacIsaac, S Roger, Richard Phoon, Kerr Pg, Andrew E. Ajani, Shaobo Tan, David Colquhoun, Amanda Mather, P. Gillard, Christophe De Block, Corinne Debroye, Francis Duyck, J.M. Krzesinski, Bruno Lapauw, V. Preumont, C. Vercammen, Zdravko Kamenov, Roza Bobeva, G. Levterov, S. Gerilovska, N. Yabrudi, Bilyana Stoyanovska-Elencheva, Z. Nikitov, Daniel Franco, Gustavo Akerman Augusto, Jean‐Pierre Salles, Luís Henrique Santos Canani, Márcio Krakauer, Maria Cerqueira, Miguel C. Riella, Hitasha Bajaj, Rolf Schlößer, Buki Ajala, Neeru P Aggarwal, R Dumas, Daniel J. O’Keefe, Sean Peterson, George Tsoukas, Chetna Tailor, Richard Tytus, Ronald Akhras, Hasnain Khandwala, Oren Steen, Diane Carbonneau, Jihoon Cha, Ann Steele, G. HOWARD BAILEY, Joseph Berlingieri, Peter Dzongowski, David Z.I. Cherney, Thomas G. Elliott, C. J. Kovacs, Pavel Hamet, BRUCE PERKINS, Karthik Tennankore, Anil Kumar Gupta, Linong Ji, Yan Li, Gongsheng Yuan, Xinzhong Dong, B. Cariou, S. Clavel, Loı̈c Le Marchand, Yves Reznik, Philippe Moulin, E. Legrand, I. Benoit Tricaud, Pierre Gourdy, Philippe Zaoui, Anne Monier, Isabelle Kazes, Dominik Dahl, Melissa M. Esser, Thilo Krüger, Ludger Rose, R. Schmieder, Alexander Segner, Young Hee Lee-Barkey, Santiago Isarria Vidal, Tobias Schürholz, Ioannis Boletis, Anastasios Raptis, Leonidas Lanaras, Emmanouil Pagkalos, John Doupis, Eleni Bekiari, Δ. Γούμενος, Dorothea Papadopoulou, Κωνσταντίνος Τζιόμαλος, Gerasimos Karousos, Maria Somali, Αthina Markou, Ioanna Zografou, I. Wittmann, Pál Brasnyó, József Balla, Gregory Petro, Marietta Baranyai, M Dudás, Sandor Vangel, L. Könyves, Szilárd Vasas, Tímea Tänczer, Mitul Shah, Bettina Anil, Anil Kumar Bhalla, MS Gireesh, Narayan Prasad, Manisha Sahay, Tukaram Jamale, Mahendra Jain, M Magdum, D. Dewan, K Dinesh, Arun Kumar, K. Jayakumar, S. Murthy, Krishnagopal Srikanth, Saurabh Gupta, Genya Aharon‐Hananel, Julio Wainstein, Gil Chernin, Irina Kenis, Roberto Trevisan, Emanuele Bosi, E. Setola, Paolo Fiorina, Giuseppe Penno, G. Pugliese, C. Giordano, Emanuela Orsi, Maria Gisella Cavallo, Katsuharu Tsuchida, T Sasaki, Hiroaki Seino, Tatsushi Kawada, Takeshi Osonoi, Hiroshi Ohashi, Yuko Shimizu, Satoru Mitomo, Chizuko Nakamura, Kimio Takai, Hajime Maeda, Hiroyuki Nishi, Yoshio Nishida, Masayo Yamada, Yoshimitsu Fukushima, Mai Kato, Masashiro Sugawara, Hideo Araki, Akito Nakagawa, Hiroyasu Onaka, Atsushi Sueyoshi, K. Kidokoro, Minoru Tanabe, Hideaki Jinnouchi, Shuji Nakamura, Sumiko Hasumi, Guillermo González-Gálvez, Carlos Aguilar Salinas, M. Morales de Teresa, R. Ortiz, Jerome I. Rotter, Saúl Irizar Santana, Si‐Keun Lim, Changwoo Yoon, Fang Tan, Bak Leong Goh, Chek Loong Loh, Nor Shaffinaz Yusoff Azmi Merican, Willem A. Bax, Daniël H. van Raalte, P. T. Luik, P. A. Marcel de Vries, Jannick A N Dorresteijn, Mazen Al‐Hakim, Sanne van Wissen, Pieter W. Kamphuisen, Jacobien C. Verhave, Janusz Gumprecht, G. Majcher-Witczak, Dorota Mlodawska-Choluj, Tomasz Stompór, W. K. Ciechanowski, Robert Małecki, Katarzyna Wasilewska, Минара Шамхаловна Шамхалова, Ludmila Ruyatkina, Gulnar Vagapova, M. Sergeeva-Kondrachenko, L. Kargina, А. Б. Песков, Elena Zhdanova, Tatyana Lysenko, Е. В. Фролова, O. Ya. Mishchenko, Lidiya Belousova, K. Astamirova, Evgeniya Antonova, Y. Pergaeva, Shamil Palyutin, A. N. Krasnopeeva, A. Tyugaeva, E. E. Krasilnikova, Е П Ромашева, Maxim Sorokin, Emil Martinka, Adriana Ilavská, L. Tomasova, K. Porubská, Dasa Skripova, I. Buganova, J. Rociakova, Jaroslav Rosenberger, A. Pavelcikova, Rudolf Smik, José Luis Górriz, Cristina Castro, Secundino Cigarrán, Carlos H. Barrios, María José Soler, Judith Martins, Apiradee Sriwijitkamol, M. Phornphutkul, Ouppatham Supasyndh, Kraiwiporn Kiattisunthorn, P. Buranasupkajorn, P. Susantitaphong, Özant Helvacı, K. Ates, Hakkı Arikan, Mustafa Arıcı, Gültekin Süleymanlar, H. Yazici, Sabahat Alışır Ecder, Özkan Güngör, Ebru Sevinç Ok, Nurhan Seyahi, Necmi Eren, Yavuz Yeniçerioğlu, О. С. Чабанна, Svetlana Panina, P. Semenovykh, V. Leonidova, Olesya Zinych, Oleg Legun, І. P. Kaydashev, Srikanth Bellary, Jacqueline Boyle, M. Chen, John McKnight, E. Pearson, Sam Philip, Santosh Sharma, James M. Wakeling, H Tindall, Ahmed Yousseif, Tak Yee Aw, A. Guerrero, Ahmed A. Arif, James A. Betts, Robert S. Busch, Cyrus Desouza, L. Gonzalez-Orozco, Carl Dukes, Jamal Hammoud, Paul R. Houser, Timothy Jackson, Zeid Kayali, Laura Young, E. Klein, P. Nicol, Stephen D. Smith, Brian D. Snyder, Eugene Soroka, C. Wysham, Ayim Akyea-Djamson, Carlos Arauz-Pacheco, A. Horeish, Alex R. Chang, Lisa Connery, Winston Gandy, Matthew P. Gilbert, Germán T. Hernández, Mark Hewitt, Derek M. Huffman, C. Lovell, Navroz Masani, Jim McGill, Imran Siddiqui, R. Perez, Joseph Reed, K. Sivalingam, Jacqueline London, Shudhanshu Kumar Saha, Abdelmoneim Awad, L. Billings, Kenneth Blaze, David Stricklin, Cynthia Brinson, Jonathan Bornfreund, Nancy McCall, Robert Buynak, K. Cannon, Nizar Daboul, Indrani Acosta, Jorge Díaz, Gregory B. Greenwood, Thomas C. Hart, Syed Shahzad Hasan, Ali Iranmanesh, R. David Koilpillai, Khalid Latif, M. Lawrence, Chen Chen, Isam Marar, C. East, Rakesh Patel, Sergio Rovner, Gilberto Seco, Z. Shaikh, Henry Traylor, Franklin J. Zieve, V Aroda, Atif Ahmed, Mihaela Biscoveanu, Matthew J. Budoff, Mohamed A. El-Shahawy, Joshua Garza, Linda L. Magnusson Hanson, Jakkidi Reddy, Henry Rodriguez, Anup Shrestha, Marializa Bernardo, Tomas Møller Christensen, Peter G. Denker, Shikhar Dua, Mahfouz El Shahawy, Alessandro S. Farias, Ruani Fernando, A. Jamal, Michael Jardula, M. Moustafa, Juan G. Posada, William Sánchez, Daura Vega-Moreno, Jayant Kumar, Sherif Sultan, Sangeeta Bansal, S. Benjamin, Osvaldo Brusco, Jeffrey D. Wayne, Rómulo Campos Gaona, O. Degani, Carolina Figueroa, M. Montero, N. Rasouli, Lawrence Zemel, George Z. Fadda, Yshay Shlesinger, David M. Charytan, David Butuk, Stanley Stringam, V. Espinosa, David D. Brandon, Herbert Shea, D. Cheung, Y. Sanchez, Yogish C. Kudva, Srinivasan Beddhu, Brian Rayner, Qasim Bhorat, Aysha Badat, Hemant Makan, M. Joshi, Marc D. Basson, Vinogran Naidoo, Aslam Amod · 发表于：Diabetes Care · 年份：2025 · DOI：10.2337/dc25-0472 · 被引用次数：16 · 研究领域：Diabetes Treatment and Management、Hormonal Regulation and Hypertension、Blood Pressure and Hypertension Studies

OBJECTIVE: In the Evaluate Renal Function With Semaglutide Once Weekly (FLOW) trial, semaglutide reduced the risk of major kidney and cardiovascular (CV) outcomes and all-cause mortality in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This prespecified analysis assessed the effects of semaglutide on kidney, CV, and mortality outcomes by baseline mineralocorticoid receptor antagonist (MRA) use. RESEARCH DESIGN AND METHODS: Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary kidney outcome was a composite of time to first persistent ≥50% eGFR reduction from baseline, kidney failure, or death from kidney/CV causes. Baseline MRA was predominantly spironolactone; finerenone was only available after recruitment ended. RESULTS: Effects were analyzed by baseline MRA use (n = 257 [136 in the semaglutide group and 121 in the placebo group]) and nonuse (n = 3,276 [1,631 in the semaglutide group and 1,645 in the placebo group]). Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; HR 0.79 [95% CI 0.68, 0.92]; P-interaction = 0.12) versus placebo in MRA and non-MRA subgroups, respectively. There was no heterogeneity, favoring the effects of semaglutide on major adverse CV events (MACE) and all-cause mortality in both MRA subgroups (P-interaction > 0.7). Albuminuria at 104 weeks was reduced from baseline with semaglutide by 15% (95...