1. Liraglutide and Renal Outcomes in Type 2 Diabetes
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Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, Buse JB, LEADER Steering Committee and Investigators. Bergenstal R, Daniels G, Moses AC, Nauck M, Nissen S, Pocock S, Steinberg W, Stockner M, Kristensen P, Ravn LS, Zychma M, Flyvbjerg A, Ford I, Kloos RT, Schactman MJ, Sleight P, Swedberg K, Tenner SM, Akalın S, Arechavaleta R, Bain S, Babkowski MC, Benroubi M, Berard L, Comlekci A, Czupryniak L, Eliasson B, Eriksson M, Fonseca V, Franek E, Gross J, Hafidh K, Haluzik M, Hayes F, Huang YY, Jacob S, Kaddaha G, Khalil A, Kilhovd B, Laakso M, Leiter L, Lalic N, Ji L, Luedemann J, Mannucci E, Marre M, Masmiquel L, Mota M, Omar M, O’Shea D, Pan C, Petrie J, Pieber T, Pratley R, Raz I, Rea R, Rutten G, Satman I, Shestakova M, Simpson R, Smith D, Tack C, Tarnow L, Thomas N, Van Gaal L, Travert F, Vidal J, Warren M, Yoon KH, Tuttle RM, Sheerman SI, Hegedüs L, Baerwald H, Bergenstal M, Celik S, Dias C, Eder M, Fitzgibbons S, Irvhage L, Kloluckova J, Kriulianski R, McDuffie R, Moen S, Paster A, Saalfeld RM, Sankar K, Shehaj E, Swierzewska P, Tiktin M, Tovey S, Gibson CM, Chakrabarti AK, Dashe JF, Hinchey J, Leary MC, Pride Y, Wiviott S, Allen S, Mehr AP, Mutter WP, Parikh S, Ray S, Cheifetz A, Leffler D, Sheth S, Alexander E, Gaglia JL, Goessling W, Mitzner LD, Rosenberg C, Snow KJ, Wagner A, Piazza G, Abell S, Davis T, D'Emden M, Ding SA, Gilfillan C, Greenaway T, Gunawan F, Ho J, Jackson R, Kalra B, Lau SL, Lin J, MacIsaac R, Makepeace A, Malabu U, Marjason J, McCallum R, McLean M, Moin N, Petersons C, Price S, Roberts A, Roberts D, Sangla K, Stranks S, Tan Y, Thynne T, Walters J, Ward G, Wen W, Zhang J, Brix J, Feder A, Höbaus C, Höllerl F, Höller V, Kotter T, Kratz E, Krzizek EC, Leb-Stoeger U, Mader J, Mras N, Novak E, Obendorf F, Peric S, Pesau G, Prager R, Ribitsch A, Schnack C, Schernthaner G, Wascher T, Batens AH, Benhalima K, De Block C, Ernest P, Fouckova A, Jandrain B, Lapauw B, Letiexhe M, Mathieu C, Neven S, Peiffer F, Ruige J, Scheen A, Taes Y, Van Boxelaer I, Vandistel G, Van Durme Y, Verhaegen A, Alencar E, Alencar R, Almeida AC, Alves B, Alves E, Alves G, Alves J, Araujo L, Arruda V, Augusto GA, Baggentoss R, Balestrassi L, Barbosa M, Barcelos I, Belem L, de Bem A, Betti RT, Bona R, Bosco A, Branda J, Bronstein M, Bueno T, Bulcão T, Caiado F, Camazzola F, Cambréa MF, Campos S, Canani L, Carra MK, Caruso S, Carvalho N, Casillo A, Castro D, Cavalcanti T, Cavichioli V, Cercato C, Chacra A, Challela W, Charchar HS, Chaves C, Chrisman C, Correia-Deur J, da Costa A Jr, Costa M, Costi B, Coutinho P, Coutinho W, Cunha MR, Daher J Jr, Davini E, Democh D Jr, Eliaschewitz F, Esmanhoto Facin G, Farias F, Felício J, Fernandes V, Filho CS, Filho FF, Filho M, Fontan D, Fontenele AP, Forti A, Franco D, Freire K, Fusaro A, Genestreti P, Gerchman F, Godi A, Gomes KF, Gonçalves P, Gonçalves R, Griz L, Grossman M, Gurgel MH, Vasconcellos Haddad AW, Halpern A, Hissa M, Inuy A, Jaime J, Jonasson T, Jorge JC, Malucelli FJ, Kohara S, Kramer C, Lacerda C, Ladeira S, Lana J, Lastebasse F, Leitão A, Leite S, Lerário AC, Lima D, Lima M, Lippi V, Lunardi M, Machado E, Maia F, Maia J, Maia KP, Mañas N, Marchisotti F, Marinho C, Martins C, Figueiredo de Medeiros F, Melo A, Melo F, Mendonca E, Mendonça P, Filho RM, Miguel M, Miléo K, Miyahara M, Montenegro AP, Moraes A, Moreira A, Ítalo Mota J, Mothe FS, Murro A, Nakatani V, Napoli TF, Neto BG, Neto OQ, Niclewicz E, Ohe LN, Oliveira F, Oliveira M, Panarotto D, Parente E, Parolin S, Pechmann L, Costa da Penha P, Perlamagna L, Perotta B, Pimentel L, Pinto M, Poço C, Ponte C, Prazeres P, Quintao E, Raduan R, Rassi DT, Rassi N, Reck L, Montenegro R Jr, Ribeiro R, Rodovalho S, Silveira Rodrigues G, Rollin G, Rossi S, Sabino C, Sales AP, Salles J, Sampaio CR, Santana L, Sato V, da Silva Santos M, Santos NL, Santos R, Saraiva J, Sartori C, Sena R, Sevilha M, Sgarbi J, Silva D, D'albuquerque Silva L, Silva ME, Siqueira K, Soares S, Sobreira W, Sousa B, Souza AC, Souza B, Tambascia M, Tarantino R, Tenor F, Tomarchio M, Triches C, Tristão LJ, Valenti A, Vasques E, Vencio S, Vianna A, Munhoz Vidotto T, Vieira 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E, Martinez G, Martinez-Miss S, Marx P, Massara L, Mastoor M, Matfin G, Maturu A, Maurides P, May M, Mayfield R, Maynard B, Mazza A, McCann K, McCoy J, McCoy T, McCullen MK, McDaniel C, McDaniel AM, McDermott M, McDonald A, McMasters B, McMurray C, Medlin T, Meinel M, Mendez I, Menefee J, Meredith M, Merriweather M, Mersey J, Messino C, Meyer S, Meyers L, Michael D, Midyett C, Miklius A, Milford E, Miller B, Miller H, Milligan M, Minor A, Miranda-Palma B, Mirarchi N, Mittadodla S, Mittle J, Moffat A, Mohaupt S, Mohiuddin K, Mokshagundam S, Monaco S, Monsaert R, Montano-Pereira C, Montgomery A, Moody K, Moon M, Moore D, Moore L, Morawski E, Moreau C, Morin D, Moscoa C, Motzkin C, Mueller R, Munoz C, Munoz M, Myneni A, Naderi B, Nagireddy P, Naidu J, Naidu R, Naik S, Naimark R, Nardicchi M, Ndukwu I, Neller C, Netten-Foster L, Neumiller J, New T, Newman S, Newton T, Nguyen B, Nicol B, Nicol P, Ninivaggi L, Niswender K, Norman L, Noworatzky G, Nyenwe E, O'Brien H, O'Connell T, Oden W, Odugbesan A, Oliver M, Oliver T, Olmeda C, O'Neil C, Oremus R, Ortega T, Ortiz-Santos S, Osborn T, Padmanabhan S, Papacostea O, Park I, Parker A, Parker K, Parker R, Patel C, Patel M, Patel R, Patino M, Patterson S, Paulson K, Paz A, Pemba R, Pepe C, Perez J, Perez T, Perry D, Phillips B, Phillips J, Pickett A, Pinson M, Pitzer R, Poduri M, Poehls J, Poteat T, Powell L, Prasad S, Prevost J, Price E, Priest D, Prieto L, Purewal T, Purighalla R, Purighalla U, Quadrel M, Qureshi A, Radhamma R, Rafla E, Rajab H, Ramalingam R, Ramirez A, Ramirez J, Ramirez K, Ramirez M, Randall M, Rangaraj U, Rao V, Rasmussen P, Rasouli N, Ray A, Reed J, Rems L, Renaud K, Reno M, Resnick M, Reusch J, Reynolds L, Rhoton K, Rhudy J, Ricci C, Rice L, Richardson A, Richardson L, Rickard H, Rickels M, Riff D, Rightenour N, Risser J, Rizvi A, Robertson J, Robinson A, Robinson R, Rockwell M, Rodriguez JP, Rodriguez M, Rojas M, Rojas W, Rooker-Morris L, Root C, Rose M, Rosenberg R, Rosenstock J, Roth M, Ruby R, Sachson R, Sack P, Sadler RK, Sahai S, Salazar J, Salgam M, Samal A, Samson A, Sanagorski R, Sanchez A, Sandberg J, Sanderson M, Sandoval J, Santiago E, Sapp T, Saunders J, Schill J, Schott C, Schreiman R, Schu D, Schuh K, Schutta M, Schwartz J, Schweppe L, Scofield H, Scribner A, Seal J, Sealock J, Seaton B, Sedlak-Hanslik T, Seekins K, Segal M, Seggelke S, Semenza S, Sentman P, Serra M, Seshadri P, Sevilla E, Shah S, Shaheen K, Shanik M, Shaw J, Sheets M, Shellabarger C, Sher J, Shippey J, Shivaswamy V, Shomali M, Shore D, Shroff P, Siddiqui T, Siegwald A, Silver R, Simmons D, Simons R, Sinan A, Singh M, Sirinvaravong S, Skero J, Slover-Zipf J, Small S, Smith B, Smith K, Smith M, Sohl J, Solarz SH, Soler D, Sood A, Sora N, Souchet A, Soule J, Sparks J, Spector L, Speicher R, Spillers L, Spivey T, Springer N, Sprouse H, St John J, Stacey A, Stacey H, Stafford M, Stagner E, Staples K, Steadman E, Steed R, Steeves G, Steinberg H, Stell C, Stirman E, Straub K, Strock E, Sue M, Suris O, Sutton T, Tabbah I, Talsania M, Tang R, Tapia J, Taylor K, Taylor-Hancher R, Teator R, Tekateka M, Temple B, Temple K, Teodori M, Tharp P, Thethi T, Theuma P, Thomas S, Thottan A, Thrasher J, Thrasher L, Tiemeyer M, Tinney I, Tobin T, Toma S, Tovar M, Townsend J, Trantow C, Traylor H, Trevino M, Troy M, Trumper D, Tryggestad J, Tucker C, Turner J, Turney R, Tuten C, Tyzack J, Ullo L, Underkofler C, Unger J, Urdanetta R, Valdivia V, Valenti S, Vanderheiden A, Vanderlinde-Wood M, Varma C, Vasquez E, Vazquez M, Vickery D, Villafuerte B, Villegas C, Vivar J, Vivekananthan K, Vo G, Vukojicic K, Wachter A, Wahl D, Waitmann J, Walker D, Walsh J, Walsh K, Walton A, Wang A, Wardell K, Watkins S, Watkinson J, Watts M, Watwe V, Weaver N, Weber R, Wedick C, Weeks D, Weeks L, Weindorff K, Weinstein R, Weiss S, Wenger K, Wentworth M, Werner A, West M, Whelan S, White B, White J, Whitmire M, Whittington R, Wical J, Wigley C, Wilkins F, Will K, Williams A, Wilson LE, Wince M, Wine S, Winkle P, Winner C, Wise J, Witte M, Wittenmyer J, Wood C, Wood R, Woodruff C, Worthington B, Wynn D, Wysham C, Xavier P, Yela S, Yenoby L, Young L, Younus N, Yourell V, Zaid M, Zubair I., Mann, Jfe, Ørsted, Dd, Brown-Frandsen, K, Marso, Sp, Poulter, Nr, Rasmussen, S, Tornøe, K, Zinman, B, Buse, Jb, Bergenstal R, LEADER Steering Committee and Investigators., Daniels, G, Moses, Ac, Nauck, M, Nissen, S, Pocock, S, Steinberg, W, Stockner, M, Kristensen, P, Ravn, L, Zychma, M, Flyvbjerg, A, Ford, I, Kloos, Rt, Schactman, Mj, Sleight, P, Swedberg, K, Tenner, Sm, Akalın, S, Arechavaleta, R, Bain, S, Babkowski, Mc, Benroubi, M, Berard, L, Comlekci, A, Czupryniak, L, Eliasson, B, Eriksson, M, Fonseca, V, Franek, E, Gross, J, Hafidh, K, Haluzik, M, Hayes, F, Huang, Yy, Jacob, S, Kaddaha, G, Khalil, A, Kilhovd, B, Laakso, M, Leiter, L, Lalic, N, Ji, L, Luedemann, J, Mannucci, E, Marre, M, Masmiquel, L, Mota, M, Omar, M, O’Shea, D, Pan, C, Petrie, J, Pieber, T, Pratley, R, Raz, I, Rea, R, Rutten, G, Satman, I, 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Resnick, M, Reusch, J, Reynolds, L, Rhoton, K, Rhudy, J, Ricci, C, Rice, L, Richardson, A, Richardson, L, Rickard, H, Rickels, M, Riff, D, Rightenour, N, Risser, J, Rizvi, A, Robertson, J, Robinson, A, Robinson, R, Rockwell, M, Rodriguez, Jp, Rodriguez, M, Rojas, M, Rojas, W, Rooker-Morris, L, Root, C, Rose, M, Rosenberg, R, Rosenstock, J, Roth, M, Ruby, R, Sachson, R, Sack, P, Sadler, Rk, Sahai, S, J, Salazar, Salgam, M, Samal, A, Samson, A, Sanagorski, R, Sanchez, A, Sandberg, J, Sanderson, M, Sandoval, J, Santiago, E, Sapp, T, Saunders, J, Schill, J, Schott, C, Schreiman, R, Schu, D, Schuh, K, Schutta, M, Schwartz, J, Schweppe, L, Scofield, H, Scribner, A, Seal, J, Sealock, J, Seaton, B, Sedlak-Hanslik, T, Seekins, K, Segal, M, Seggelke, S, Semenza, S, Sentman, P, Serra, M, Seshadri, P, Sevilla, E, Shah, S, Shaheen, K, Shanik, M, Shaw, J, Sheets, M, Shellabarger, C, Sher, J, Shippey, J, Shivaswamy, V, Shomali, M, Shore, D, Shroff, P, Siddiqui, T, Siegwald, A, Silver, R, Simmons, D, 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- Subjects
Male ,Settore MED/09 - Medicina Interna ,Acute Kidney Injury ,Aged ,Albuminuria ,Creatinine ,Diabetes Mellitus, Type 2 ,Diabetic Nephropathies ,Double-Blind Method ,Female ,Follow-Up Studies ,Glomerular Filtration Rate ,Glucagon-Like Peptide 1 ,Humans ,Hypoglycemic Agents ,Intention to Treat Analysis ,Kidney Failure, Chronic ,Liraglutide ,Middle Aged ,Type 2 diabetes ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,GLOMERULAR-FILTRATION-RATE ,KIDNEY-FUNCTION ,DISEASE ,law.invention ,Kidney Failure ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Medicine ,Settore MED/49 - Scienze Tecniche Dietetiche Applicate ,Chronic ,RISK ,Kidney ,Acute kidney injury ,11 Medical And Health Sciences ,General Medicine ,medicine.anatomical_structure ,TRIAL ,liraglutide, randomized controlled trial, type 2 diabetes, renal outcomes ,Life Sciences & Biomedicine ,Type 2 ,medicine.drug ,medicine.medical_specialty ,Renal function ,030209 endocrinology & metabolism ,CARDIOVASCULAR OUTCOMES ,Follow-Up Studie ,03 medical and health sciences ,Medicine, General & Internal ,General & Internal Medicine ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,Intensive care medicine ,Science & Technology ,business.industry ,MORTALITY ,medicine.disease ,INTENSIVE GLUCOSE CONTROL ,INDIVIDUALS ,chemistry ,Diabetic Nephropathie ,LEADER Steering Committee and Investigators ,business - Abstract
BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).
- Published
- 2017