PMID- 24965700 OWN - NLM STAT- MEDLINE DCOM- 20150514 LR - 20220409 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 16 IP - 10 DP - 2014 Oct TI - Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes mellitus and chronic kidney disease. PG - 1016-27 LID - 10.1111/dom.12348 [doi] AB - AIM: This study evaluated the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and within a subset of Stage 3 chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] >/= 30 and <50 ml/min/1.73 m(2)). METHODS: In this 52-week, randomized, double-blind, placebo-controlled study, patients (N = 269; mean eGFR, 39.4 ml/min/1.73 m(2)) received canagliflozin 100 or 300 mg and placebo once daily. Efficacy endpoints included changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and systolic blood pressure (BP); adverse events (AEs) were also recorded. RESULTS: At week 52, canagliflozin 100 and 300 mg reduced HbA1c compared with placebo (-0.19, -0.33 and 0.07%, respectively); placebo-subtracted differences (95% confidence interval) were -0.27% (-0.53, 0.001) and -0.41% (-0.68, -0.14). Canagliflozin also lowered FPG, body weight and BP versus placebo. Overall AE incidence was 85.6, 80.9, and 86.7% with canagliflozin 100 and 300 mg and placebo, respectively. Osmotic diuresis-related AEs were more common with both canagliflozin doses, and incidences of urinary tract infections and volume depletion-related AEs were higher with canagliflozin 300 mg versus placebo. Decreases in eGFR (-2.1, -4.0 and -1.6 ml/min/1.73 m(2)) were seen with canagliflozin 100 and 300 mg compared with placebo. Canagliflozin 100 and 300 mg provided median percent reductions in urine albumin to creatinine ratio versus placebo (-16.4, -28.0 and 19.7%). CONCLUSIONS: Canagliflozin improved glycaemic control and was generally well tolerated in patients with T2DM and within a subset of Stage 3 CKD over 52 weeks. CI - (c) 2014 John Wiley & Sons Ltd. FAU - Yale, J-F AU - Yale JF AD - Department of Medicine, Royal Victoria Hospital and McGill University, Montreal, Canada. FAU - Bakris, G AU - Bakris G FAU - Cariou, B AU - Cariou B FAU - Nieto, J AU - Nieto J FAU - David-Neto, E AU - David-Neto E FAU - Yue, D AU - Yue D FAU - Wajs, E AU - Wajs E FAU - Figueroa, K AU - Figueroa K FAU - Jiang, J AU - Jiang J FAU - Law, G AU - Law G FAU - Usiskin, K AU - Usiskin K FAU - Meininger, G AU - Meininger G CN - DIA3004 Study Group LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140722 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (SLC5A2 protein, human) RN - 0 (Sodium-Glucose Transporter 2) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Thiophenes) RN - 0SAC974Z85 (Canagliflozin) SB - IM MH - Aged MH - Blood Glucose/drug effects MH - Blood Pressure/drug effects MH - Body Weight/drug effects MH - Canagliflozin MH - Diabetes Mellitus, Type 2/blood/*drug therapy/physiopathology MH - Diabetic Nephropathies/blood/*drug therapy/physiopathology MH - Disease Progression MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Glomerular Filtration Rate/drug effects MH - Glucosides/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Renal Insufficiency, Chronic/blood/*drug therapy/physiopathology MH - Sodium-Glucose Transporter 2/drug effects MH - *Sodium-Glucose Transporter 2 Inhibitors MH - Thiophenes/*therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - diabetic nephropathy OT - randomized trial OT - sodium glucose co-transporter 2 (SGLT2) inhibitor OT - type 2 diabetes mellitus FIR - Ansari, Anwar IR - Ansari A FIR - Arnouts, Paul IR - Arnouts P FIR - Assefi, Ali IR - Assefi A FIR - Barreto, Angelique IR - Barreto A FIR - Barysheva, Olga IR - Barysheva O FIR - Bavanandam, Sunita IR - Bavanandam S FIR - Blaze, Kenneth IR - Blaze K FIR - Bochenek, Anna IR - Bochenek A FIR - Bononi, Patricia IR - Bononi P FIR - Booth, William IR - Booth W FIR - Boyarkin, Mikhail IR - Boyarkin M FIR - Burgess, Lesley IR - Burgess L FIR - Busch, Klaus IR - Busch K FIR - Buse, John IR - Buse J FIR - Cariou, Bertrand IR - Cariou B FIR - Carranza, Jaime IR - Carranza J FIR - Cha, Bongsoo IR - Cha B FIR - Chang, Anna IR - Chang A FIR - Clavel, Sylvaine IR - Clavel S FIR - Cockrell, Robert C IR - Cockrell RC FIR - Conway, James IR - Conway J FIR - Cook, William IR - Cook W FIR - Dande, Ajay IR - Dande A FIR - De Los Rios, Manuel Odin IR - De Los Rios MO FIR - Deshmukh, Vaishali IR - Deshmukh V FIR - Dobjanschi, Carmen IR - Dobjanschi C FIR - Dotta, Francesco IR - Dotta F FIR - Elliott, Thomas IR - Elliott T FIR - Ellis, Graham IR - Ellis G FIR - Ferraro, Robert IR - Ferraro R FIR - Fishman, Norman IR - Fishman N FIR - Fomin, Viktor IR - Fomin V FIR - Fraige Filho, Fadlo IR - Fraige Filho F FIR - Gagiu, Remus IR - Gagiu R FIR - Goh, Bak Leong IR - Goh BL FIR - Goldenberg, Ronald IR - Goldenberg R FIR - Gorriz, Jose Luis IR - Gorriz JL FIR - Gottschlich, Gregory IR - Gottschlich G FIR - Gouet, Didier IR - Gouet D FIR - Grenfell, Raymond IR - Grenfell R FIR - Griffin, Carl IR - Griffin C FIR - Guarisco, Michael IR - Guarisco M FIR - Guerci, Bruno IR - Guerci B FIR - Henkel, Elena IR - Henkel E FIR - Hramiak, Irene IR - Hramiak I FIR - Ison, Rodney IR - Ison R FIR - Jadoul, Michel IR - Jadoul M FIR - Jang, Hakchul IR - Jang H FIR - Januszewicz, Andrzej IR - Januszewicz A FIR - Kale, Shailaja IR - Kale S FIR - Karpova, Irina IR - Karpova I FIR - Kaye, William IR - Kaye W FIR - Kerstein, Howard IR - Kerstein H FIR - Kijanska, Janina IR - Kijanska J FIR - Kobalava, Zhanna IR - Kobalava Z FIR - Kong, Norella IR - Kong N FIR - Krasilnikova, Elena IR - Krasilnikova E FIR - Krebs, Jeremy IR - Krebs J FIR - Kuczerowski, Roman IR - Kuczerowski R FIR - Kuzin, A IR - Kuzin A FIR - Kuzmenko, Alexandr IR - Kuzmenko A FIR - Laurens, Wim IR - Laurens W FIR - Lim, Soo Kun IR - Lim SK FIR - Marasaev, Vyacheslav IR - Marasaev V FIR - Castelao, Alberto Martinez IR - Castelao AM FIR - Merker, Ludwig IR - Merker L FIR - Michlin, Bernard IR - Michlin B FIR - Morales, Enrique IR - Morales E FIR - Motylev, Igor IR - Motylev I FIR - Muse, Derek IR - Muse D FIR - Mutha, Abhay IR - Mutha A FIR - Neto, Elias Davi IR - Neto ED FIR - Nicholls, Kathy IR - Nicholls K FIR - Niemetz, Ingo IR - Niemetz I FIR - Iglesias, Javier Nieto IR - Iglesias JN FIR - Ong, Loke Meng IR - Ong LM FIR - Onor, Gabriel IR - Onor G FIR - Packham, David IR - Packham D FIR - Petit, Catherine IR - Petit C FIR - Piatti, Marco IR - Piatti M FIR - Pirags, Valdis IR - Pirags V FIR - Poch, Esteban IR - Poch E FIR - Ramirez, German IR - Ramirez G FIR - Riser, James IR - Riser J FIR - Roger, Simon IR - Roger S FIR - Ross, Stuart IR - Ross S FIR - Rudolph, Lance IR - Rudolph L FIR - Sangumani, Jeyaraman IR - Sangumani J FIR - Schollum, John IR - Schollum J FIR - Scott, Russell IR - Scott R FIR - Sebopa, Boitumelo IR - Sebopa B FIR - Serafinceanu, Cristian IR - Serafinceanu C FIR - Serusclat, Pierre IR - Serusclat P FIR - Seufert, Jochen IR - Seufert J FIR - Siegmund, Thorsten IR - Siegmund T FIR - Silva, Arnold IR - Silva A FIR - Skokowska, Ewa IR - Skokowska E FIR - Smith, Diane IR - Smith D FIR - Sokolova, Jelena IR - Sokolova J FIR - Solovyov, Oleg IR - Solovyov O FIR - Steindorf, Jorg IR - Steindorf J FIR - Stringam, Stanley IR - Stringam S FIR - Teterovska, Dace IR - Teterovska D FIR - Thivolet, Charles IR - Thivolet C FIR - Tytus, Richard IR - Tytus R FIR - Vally, Tasneem IR - Vally T FIR - Van Vlem, Bruno IR - Van Vlem B FIR - Vercammen, Chris IR - Vercammen C FIR - Volkova, Natalya IR - Volkova N FIR - Warling, Xavier IR - Warling X FIR - Winkler, Lee IR - Winkler L FIR - Yale, Jean-Francois IR - Yale JF FIR - Young, Simon IR - Young S FIR - Yue, Dennis IR - Yue D FIR - Zanella, Maria Tereza IR - Zanella MT FIR - Zimmerer, Michael IR - Zimmerer M EDAT- 2014/06/27 06:00 MHDA- 2015/05/15 06:00 CRDT- 2014/06/27 06:00 PHST- 2014/03/17 00:00 [received] PHST- 2014/06/10 00:00 [revised] PHST- 2014/06/14 00:00 [accepted] PHST- 2014/06/27 06:00 [entrez] PHST- 2014/06/27 06:00 [pubmed] PHST- 2015/05/15 06:00 [medline] AID - 10.1111/dom.12348 [doi] PST - ppublish SO - Diabetes Obes Metab. 2014 Oct;16(10):1016-27. doi: 10.1111/dom.12348. Epub 2014 Jul 22.