Empagliflozin and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus, Established Cardiovascular Disease, and Chronic Kidney Disease
- Authors
- Wanner, Christoph; Lachin, John M.; Inzucchi, Silvio E.; Fitchett, David; Mattheus, Michaela; George, Jyothis; Woerle, Hans J.; Broedl, Uli C.; von Eynatten, Maximilian; Zinman, Bernard; Aizenberg, D.; Ulla, M.; Waitman, J.; De Loredo, L.; Farias, J.; Fideleff, H.; Lagrutta, M.; Maldonado, N.; Colombo, H.; Ferre Pacora, F.; Wasserman, A.; Maffei, L.; Lehman, R.; Selvanayagam, J.; d'Emden, M.; Fasching, P.; Paulweber, B.; Toplak, H.; Luger, A.; Drexel, H.; Prager, R.; Schnack, C.; Schernthaner, G.; Fliesser-Goerzer, E.; Kaser, S.; Scheen, A.; Van Gaal, L.; Hollanders, G.; Kockaerts, Y.; Capiau, L.; Chachati, A.; Persu, A.; Hermans, M.; Vantroyen, D.; Vercammen, C.; Van de Borne, P.; Mathieu, C.; Benhalima, K.; Lienart, F.; Mortelmans, J.; Strivay, M.; Vereecken, G.; Keymeulen, B.; Lamkanfi, F.; Chacra, A.; Eliaschewitz, F.; Zanella, M.; Faludi, A.; Bertolami, M.; Hayashida, C.; Nunes Salles, J.; Monte, O.; Dinato, M.; Manenti, E.; Rassi, N.; Halpern, A.; Lima Filho, M.; Ayoub, J.; Felicio, J.; Borges, J.; Gross, J.; Sgarbi, J.; Betti, R.; Tiburcio, A.; Purisch, S.; Schmid, H.; Takahashi, M.; Castro, M.; Rea, R.; Hissa, M.; Geloneze Neto, B.; Saraiva, J.; Henein, S.; Lochnan, H.; Imran, S. A.; Clayton, D.; Bayly, K.; Berlingieri, J.; Boucher, P.; Chan, Y.; Gupta, M.; Chehayeb, R.; Ouellett, A.; Ur, E.; Woo, V.; Zinman, B.; St Amour, E.; Terront Lozano, M.; Yupanqui Lozno, H.; Urina, M.; Lopez Jaramillo, P.; Jaramillo, N.; Sanchez, G.; Perez, G.; Tusek, S.; Mirosevic, G.; Goldoni, V.; Jurisic-Erzen, D.; Balasko, A.; Balic, S.; Drvodelic-Sunic, E.; Varzic, S. Canecki; Machkova, M.; Weiner, P.; Lastuvka, J.; Olsovsky, J.; Krarup, T.; Ridderstrale, M.; Tarnow, L.; Boesgaard, T. Wellov; Lihn, A. Saetre; Christensen, P.; Juhl, H.; Urhammer, S.; Lund, P.; Adojaan, B.; Jakovlev, U.; Lanno, R.; Lubi, M.; Marandi, T.; Gouet, D.; Courreges, J.; Zaoui, P.; Choukroun, G.; Petit, C.; Formagne, L.; Estour, B.; Mabire, P.; Daugenet, C.; Lemarie, B.; Clavel, S.; Aure, P.; Remaud, P.; Halimi, J.; Hadjadj, S.; Couffinhal, T.; Glonti, S.; Metreveli, D.; Lominadze, Z.; Giorgadze, E.; Burtchuladze, T.; Javashvili, L.; Kurashvili, G.; Kurashvili, R.; Virsaladze, D.; Nadareishvili, L.; Khomasuridze, A.; Cahill, T.; Green, F.; MacRury, S.; Waldron, M.; Middleton, A.; McKnight, J.; Pearson, E.; Butler, M.; Choksi, M.; Caldwell, I.; Farmer, I.; Wyatt, N.; Patrick, J.; O'Brien, I.; Devers, M.; Bousboulas, S.; Pappas, S.; Piaditis, G.; Vryonidou, A.; Tentolouris, N.; Karamitsos, K.; Manes, C.; Benroubi, M.; Avramidis, I.; Ozaki, R.; Tan, K.; Siu, S.; Tsang, C.; Dudas, M.; Nagy, K.; Salamon, C.; Ip, T.; Geroo, L.; Patkay, J.; Tabak, A.; Juhasz, F.; Szentpeteri, I.; Tamas, G.; Ghaisas, N.; Bantwal, G.; Mohan, V.; Gupta, J.; Sadhu, N.; Kulkarni, A.; Garg, N.; Reddy, S.; Deshpande, N.; Gutlapalli, K.; Pillai, M.; Premchand, R.; Badgandi, M.; Jain, S.; Aravind, S.; Shamanna, P.; Pandey, A.; Gupta, S.; Pramono, B.; Saksono, H. Dante; Agung, P.; Wahono, S. Djoko; Suastika, K.; Tanggo, Y.; Juwana, Y.; Siswanto, B.; Adawi, F.; Efrati, S.; Mazen, E.; Bashkin, A.; Herskovits, T.; Jaffe, A.; Schiff, E.; Wainstein, J.; Taddei, S.; Aiello, A.; Arca, M.; Calabro, P.; Cignarelli, M.; Fioretto, P.; Reggiani, G. Marchesini; Gnasso, A.; Marchionni, N.; Marsilii, A.; Bucci, M.; Mezzetti, A.; Pozzilli, P.; Colivicchi, F.; Santini, M.; Moro, E.; Toscano, V.; Fucili, A.; Semplicini, A.; Monno, S.; Furui, K.; Higashiue, S.; Hiramatsu, N.; Kawamitsu, K.; Takenaka, T.; Takahashi, H.; Hojo, F.; Onishi, Y.; Izumino, K.; Okubo, M.; Wakida, Y.; Kondo, Y.; Hieshima, K.; Jinnouchi, H.; Suzuki, A.; Ito, M.; Park, S.; Kim, Y.; Hong, T.; Park, H.; Gwon, H.; Kim, H.; Kang, K.; Jeong, M.; Seung, K.; Lim, D.; Rha, S.; Tahk, S.; Yang, J.; Yoon, J.; Shin, M.; Kim, D.; Jeong, J.; Ahmad, N. Nik; Mustafa, N.; Mohamed, W. Wan; Fung, Y.; Ghani, R. Abdul; Chandramouli, A.; Chee, K.; Kadir, K. Abdul; Ling, K.; Abu Hassan, M.; Foo, S.; Lee, S.; Garcia Hernandez, P.; Aguilar-Salinas, C.; Vidrio Velazquez, M.; Flores, F.; Alpizar Salazar, M.; Micher Escalante, D.; Garcia Soria, M.; Cardona Munoz, E.; Storms, G.; Schaper, N.; Kooy, A.; Krekels, M.; van Bemmel, T.; Verhoeven, R.; Mulder, H.; Oldenburg-Ligtenberg, P.; Gonkel, F.; de Jong, A.; van Soest, J.; Viergever, P.; Mevissen, H.; Lochorn, G.; Zwiers, G.; Hoogslag, P.; Ronner, E.; Nierop, P.; Al-Windy, N.; Kragten, J.; Dekelver, P.; Benatar, J.; Krebs, J.; Scott, R.; Heggen, E.; Berz, A.; Fossum, C.; Hurtig, U.; Langslet, G.; Baranowski, M.; Sparby, J.; Karlsson, T.; Karlsson, Thomas; Delgado Torres, C.; Rodriguez Escudero, A.; Lisson, R.; Allemant Maldonado, A.; Gallardo Rojas, W.; Gonzales Bravo, L.; Lema Osores, J.; Farfan, J.; Zapata, L.; Godoy Junchaya, J.; Roldan Concha, Y.; Urquiaga Calderon, J.; Sy, R.; Tan, G.; Aquitania, G.; De Los Santos, G.; Panelo, A.; Roderos, O.; Rosales, R.; Toledo, R.; Liwag, A.; Ramoncito, H.; Skokowska, E.; Krzyzagorska, E.; Ogorek, M.; Wojnowski, L.; Spyra, J.; Konieczny, M.; Piesiewicz, W.; Kus, W.; Ocicka-Kozakiewicz, A.; Orlowska-Kunikowska, E.; Zmuda, W.; Duarte, S.; Leitao, A.; Monteiro, P.; Rita, H.; Salgado, V.; Pinto, L.; Queiros, J.; Teixeira, J.; Rogado, C.; Duarte, R.; Sobral do Rosario, F.; Silva, A.; Andrade, L.; Velez, M.; Brazao, M.; Istratoaie, O.; Lichiardopol, R.; Catrinoiu, D.; Militaru, C.; Zetu, C.; Barbonta, D.; Cosma, D.; Crisan, C.; Pop, L.; Esip, V.; Khetagurova, F.; Petrov, A.; Arutyunov, G.; Boyarkin, M.; Agafyina, A.; Vorokhobina, N.; Petunina, N.; Libov, I.; Zalevskaya, A.; Nikolaev, K.; Barbarash, O.; Potemkin, V.; Bystrova, A.; Krasilnikova, E.; Barbarich, V.; Chumakova, G.; Tarasov, N.; Meleshkevich, T.; Zateyshchikov, D.; Lantseva, O.; Belenkiy, D.; Obrezan, A.; Rossolko, L.; Fillipova, E.; Yakhontova, P.; Khokhlov, A.; Tan, R.; Sum, C.; Chang, H.; Distiller, L.; Pretorius, M.; Nortje, H.; Mitha, E.; Burgess, L.; Blignaut, S.; Venter, T.; Moodley, R.; Lombaard, J.; Govind, U.; Naidoo, V.; Mookadam, M.; Engelbrecht, J.; Omar, M.; Jurgens, J.; Podgorski, G.; Vawda, H.; Naidoo, D.; Emanuel, S.; Roodt, A.; Amod, A.; Van Zyl, L.; Segura, J.; Brito, M.; Fernandez-Cruz, A.; Artola, S.; Iglesias, R.; Toural, E.; Garcia-Ortiz, L.; Saban, J.; Mesa, J.; Vidal, J.; Linares, J.; del Canizo, F.; Rigla, M.; Suarez, C.; Llorente, I.; Moreno, B.; Antoli, A.; Gomez Peralta, F.; Iglesias, M.; Pereg, V.; de Teresa, L.; Camafort, M.; Trescoli, C.; Satarasinghe, R.; Somasundaram, N.; Siyambalapitiya, S.; Antonypillai, C.; Bulugahapitiya, D.; Medagama, U.; Huang, C.; Lu, Y.; Hwang, J.; Chiang, C.; Wen, M.; Chen, J.; Lai, W.; Chang, K.; Wang, J.; Yeh, H.; Kriangsak, P.; Deerochanawong, C.; Suwanwalaikorn, S.; Mangklabruks, A.; Kaewsuwanna, P.; Piyayotai, D.; Iabluchanskyi, M.; Samoylov, O.; Godlevska, O.; Kovalyova, O.; Voloshyna, O.; Tseluyko, V.; Zotov, S.; Vykhovanyuk, I.; Dulgeroff, A.; Mayfield, R.; Zaniewski-Singh, M.; Ullal, J.; Aloi, J.; De La Rosa, R.; Mosely, J.; Wittmer, B.; Aronoff, S.; Rosenfeld, J.; Seidner, M.; Warren, M.; Fishman, N.; Weiss, R.; Arif, A.; Sandberg, M.; Lewis, D.; Ball, E.; Graf, R.; Breton, C.; Tamayo, R.; Richards, R.; Cefalu, W.; Uwaifo, G.; Zayour, D.; Hoffman, J.; Fitz-Patrick, D.; Khan, B.; Blaze, K.; Bressler, P.; Halpern, S.; Chappell, D.; Bergenstal, R.; Cuddihy, R.; Matfin, G.; Freedman, Z.; Gonzalez-Campoy, J.; Lerman, S.; Rendell, M.; Sitar, S.; Reeves, M.; Howard, T.; Soufer, J.; Miranda-Palma, B.; Laliotis, A.; Shomali, M.; Teltser, M.; Hurley, D.; Morawski, E.; Cherlin, R.; Houchin, V.; Welch, M.; Goytia-Leos, D.; Syed, M.; Kowaloff, E.; Weinrauch, L.; Peniston, J.; Brockmyre, A.; First, B.; Feld, L.; Huffman, D.; Nassim, O.; Gottschlich, G.; Patel, A.; Knopke, C.; Hernandez, M.; Diaz, J.; Giugliano, G.; Nicasio, J.; Eagerton, D.; Huntley, R.; Reed, J., III; Magee, M.; Hippert, R.; Sofley, C., Jr.; Alzohaili, O.; Levins, P.; Anspach, R.; Shah, S.; Brusco, O.; Naidu, J.; Lindenbaum, J.; Jacks, R.; Hammond, G.; Arena, C.; Saxman, K.; Mach, M.; Kerstein, H.; Kereiakes, D.; Wahlen, J.; Wehmeier, K.; Chaykin, L.; Rothman, J.; Fogelfeld, L.; Stroger, John H., Jr.; Bittar, N.; Rosenstock, J.; Kayne, D.; Navarro, J.; Colfer, H.; Mokshagundam, S.; Shandilya, L.; Connery, L.; Wysham, C.; Dela Llana, A.; Jardula, M.; MacAdams, M.; Flippo, G.; Heurich, E.; Curtis, C.; Sanders, D.; Rawls, R.; Velazquez, F.; Osea, E.; Mahood, K.; Feldman, G.; Eder, F.; Riley, E.; Fowler, W.; Jain, M.; Shepard, M.; Schear, M.; Barker, B.; Strout, C.; Obiekwe, O.; Shanik, M.; Green, C.; Blakney, E.; Roberson, K.; Bretton, E.; Pish, R.; Kaveh, K.; Maynard, B.; Barager, W.; Soldyshev, R.; Austin, B.; Parmar, P.; Simpson, R.; Chauhan, A.; Kasper, J.; Burr, R.; Patel, N.; Mariano, H.; Pluto, T.; Bratcher, C.; Juarez, M.; Levinson, L.; Awad, A.; Longshaw, K.; Hoffman, K.; Richwine, R.; Molter, D.; Boscia, J., III; Kowalyk, S.; Lemis, P.; Liss, J.; Orr, R.; Riser, J.; Wood, J.; Ubani, A.; Paine, W.; Hassani, F.; Miranda, F.; Hansen, V.; Hansen, Val R.; Farris, N.; Bowden, R.; Ajani, D.; Maw, K.; Andersen, J.; Bergman, B.; Dunmyer, S.; Brandon, D.; Anderson, M.; Bononi, P.; Prawer, J.; Seidman, B.; Cruz, H.; Wilks, K.; DiSanto, L.; Buynak, R.; Christensen, T.; Denker, P.; Koppel, W.; Stedman, M.; Lewy-Alterbaum, L.; Karim, S.; Shapiro, J.; Gardner, T.; Oskin, T.; Gabra, N.; Malano, J.
- Issue Date
- Jan-2018
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Keywords
- diabetes mellitus, type 2; hospitalization; kidney diseases; mortality; sodium-glucose transporter 2; treatment outcome
- Citation
- CIRCULATION, v.137, no.2, pp.119 - 129
- Journal Title
- CIRCULATION
- Volume
- 137
- Number
- 2
- Start Page
- 119
- End Page
- 129
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/82442
- DOI
- 10.1161/CIRCULATIONAHA.117.028268
- ISSN
- 0009-7322
- Abstract
- BACKGROUND: Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus and established cardiovascular disease in the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients). Urinary glucose excretion with empagliflozin decreases with declining renal function, resulting in less potency for glucose lowering in patients with kidney disease. We investigated the effects of empagliflozin on clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease. METHODS: Patients with type 2 diabetes mellitus, established cardiovascular disease, and estimated glomerular filtration rate (eGFR) >= 30 mL.min(-1).1.73 m(-2) at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. We analyzed cardiovascular death, hospitalization for heart failure, all-cause hospitalization, and all-cause mortality in patients with prevalent kidney disease (defined as eGFR < 60 mL.min(-1).1.73 m(-2) and/o r urine albumin-creatinine ratio > 300 mg/g) at baseline. Additional analyses were performed in subgroups by baseline eGFR (< 45, 45-< 60, 60-<90, >= 90 mL.min(-1).1.73 m(-2)) and baseline urine albumin-creatinine ratio (> 300, 30-<= 300, < 30 mg/g). RESULTS: Of 7020 patients treated, 2250 patients had prevalent kidney disease at baseline, of whom 67% had a diagnosis of type 2 diabetes mellitus for > 10 years, 58% were receiving insulin, and 84% were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. In patients with prevalent kidney disease at baseline, empagliflozin reduced the risk of cardiovascular death by 29% compared with placebo (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.98), the risk of all-cause mortality by 24% (HR, 0.76; 95% CI, 0.59-0.99), the risk of hospitalization for heart failure by 39% (HR, 0.61; 95% CI, 0.42-0.87), and the risk of all-cause hospitalization by 19% (HR, 0.81; 95% CI, 0.72-0.92). Effects of empagliflozin on these outcomes were consistent across categories of eGFR and urine albumin-creatinine ratio at baseline and across the 2 doses studied. The adverse event profile of empagliflozin in patients with eGFR < 60 mL.min-1.1.73 m-2 was consistent with the overall trial population. CONCLUSIONS: Empagliflozin improved clinical outcomes and reduced mortality in vulnerable patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/82442)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.