Data di Pubblicazione:
2019
Abstract:
BACKGROUND: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS: In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS: The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P = 0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P = 0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P = 0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS: In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.).
Tipologia CRIS:
14.a.1 Articolo su rivista
Keywords:
Aged; Canagliflozin; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Double-Blind Method; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Sodium-Glucose Transporter 2 Inhibitors
Elenco autori:
Perkovic, V; Mahaffey, Kw; Agarwal, R; Bakris, G; Brenner, Bm; Cannon, Cp; Charytan, Dm; de Zeeuw, D; Greene, T; Jardine, Mj; Heerspink, Hjl; Levin, A; Meininger, G; Neal, B; Pollock, C; Wheeler, Dc; Zhang, H; Zinman, B; Mcguire, Dk; Holman, R; Home, P; Scharfstein, D; Parfrey, P; Shahinfar, S; August, P; Chang, T; Sinha, Ad; Januzzi, J; Kolansky, D; Amerena, J; Hillis, G; Gorelick, P; Kissela, B; Kasner, S; Lindley, R; Fulcher, G; Ounadjela, S; Hufert, K; von Ingersleben, G; Gaglia, J; Harris, R; Hudson, M; Turchin, A; Cheifetz, A; Sheth, S; Feuerstein, J; Cohen, S; Jardine, M; Li, N; Kolesnyk, I; Aizenberg, D; Pecoits-Filho, R; Cherney, D 3rd; Obrador, G; Chertow, G; Hawley, C; Ji, L; Wada, T; Jha, V; Lim, Sk; Lim-Abrahan, Ma; Santos, F; Chae, Dw; Hwang, Sj; Vazelov, E; Rychlík, I; Hadjadj, S; Krane, V; Rosivall, L; De Nicola, L; Dreval, A; Nowicki, M; Schiller, A; Distiller, L; Górriz, Jl; Kolesnyk, M; Morren, F; Goykhman, S; David, C; Yost, L; Wang, H; Hettiarachchi, M; Thimmaiah, R; Koppolu, D; George, S; Schmidt, M; Ignjatovic, J; Chapin, L; Travis, K; Destree, M; Sood, V; Coffee, L; De Brouwer, K; Zaviriukha, V; Starzec, A; Koizumi, M; Lin, G; Chen, E; Lin, P; Leia, C; Mascaro, D; Amigo, A; Limos, A; Abrahamsen, I; Jaffer, S; Ahuad Guerrero, Ra; Albisu, Jp; Alvarisqueta, A; Bartolacci, I; Berli, Ma; Bordonava, A; Calella, P; Cantero, Mc; Cartasegna, Lr; Cercos, E; Coloma, Gc; Colombo, H; Commendatore, V; Cuadrado, J; Cuneo, Ca; Cusumano, Am; Douthat, Wg; Dran, Rd; Farias, E; Fernandez, Mf; Finkelstein, H; Fragale, G; Fretes, Jo; Garcia, Nh; Gastaldi, A; Gelersztein, E; Glenny, Ja; Gonzalez, Jp; Gonzalez Colaso, Pdc; Goycoa, C; Greloni, Gc; Guinsburg, A; Hermida, S; Juncos, Li; Klyver, Mi; Kraft, F; Krynski, F; Lanchiotti, Pv; Leon de la Fuente, Ra; Marchetta, N; Mele, P; Nicolai, S; Novoa, Pa; Orio, Si; Otreras, F; Oviedo, A; Raffaele, P; Resk, Jh; Rista, L; Rodriguez Papini, N; Sala, J; Santos, Jc; Schiavi, Lb; Sessa, H; Smith Casabella, T; Ulla, Mr; Valdez, M; Vallejos, A; Villarino, A; Visco, Ve; Wassermann, A; Zaidman, Cj; Cheung, Nw; Droste, C; Fraser, I; Johnson, D; Mah, Pm; Nicholls, K; Packham, D; Proietto, J; Roberts, A; Roger, S; Tsang, V; Raduan, Ra; Alves da Costa, Fa; Amodeo, C; Andreotti Turatti, La; Bregman, R; Camelo Sanches, Fc; Canani, Lh; Chacra, Ar; Cunha Borges, Jl; Cunha Vêncio, Sa; da Silva Franco, Rj; D'Avila, D; de Souza Portes, E; de Souza, P; Deboni, Lm; Filho, Ff; Geloneze Neto, B; Gomes, M; Kohara, Sk; Keitel, E; Kerr Saraiva, Jf; Kurtz Lisboa, Hr; de Carvalho Contieri, Fl; Milagres, R; Montenegro Junior, R; Moreira de Brito, C; Nazzer Hissa, M; Nazario Sabbag, Âr; Noronha, I; Panarotto, D; Pecoits Filho, R; Pereira, Ma; Saporito, W; Scotton, As; Schuch, T; Simões de Almeida, R; Slompo Ramos, C; Soares Felício, J; Thomé, F; Tibes Hachmann, Jc; Yamada, S; Yoiti Hayashida, C; Zanata Petry, Tb; Zanella, Mt; Andreeva, V; Angelova, A; Dimitrov, S; Genadieva, V; Genova-Hristova, G; Hristozov, K; Kamenov, Z; Koundurdjiev, A; Lozanov, L; Margaritov, V; Nonchev, B; Rangelov, R; Shinkov, A; Temelkova, M; Velichkova, E; Yakov, A; Aggarwal, N; Aronson, R; Bajaj, H; Chouinard, G; Conway, J; Cournoyer, S; Daroza, G; De Serres, S; Dubé, F; Goldenberg, R; Gupta, A; Gupta, M; Henein, S; Khandwala, H; Leiter, L; Madore, F; Mcmahon, A; Muirhead, N; Pichette, V; Rabasa-Lhoret, R; Steele, A; Tangri, N; Torshizi, A; Woo, V; Zalunardo, N; Fernández Montenegro, Ma; Godoy Jorquera, Jg; Medina Fariña, M; Saavedra Gajardo, V; Vejar, M; Chen, N; Chen, Q; Gan, S; Kong, Y; Li, D; Li, W; Li, X; Lin, H; Liu, J; Lu, W; Mao, H; Ren, Y; Song, W; Sun, J; Sun, L; Tu, P; Wang, G; Yang, J; Yin, A; Yu, X; Zhao, M; Zheng, H; Accini Mendoza, Jl; Arcos, E; Avendano, J; Diaz Ruiz, Jea; Garcia Ortiz, Lh; Gonzalez, A; Hernandez Triana, E; Higuera, Jd; Malaver, N; Molina de Salazar, Di; Rosero, R; Terront Lozano, Ma; Valderrama Cometa, L; Valenzuela, A; Vargas Alonso, Rd; Villegas, I; Yup
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