PMID- 26450639 OWN - NLM STAT- MEDLINE DCOM- 20161114 LR - 20221207 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 18 IP - 1 DP - 2016 Jan TI - Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes. PG - 82-91 LID - 10.1111/dom.12589 [doi] AB - AIMS: To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist]. METHODS: CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. RESULTS: Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [-0.56% (95% confidence interval [CI]: -0.77, -0.35), and -0.75% (95% CI: -0.95, -0.54), respectively] and GLP-1 receptor agonists [-1.00% (95% CI: -1.35, -0.65), and -1.06% (95% CI: -1.43, -0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis-related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues. CONCLUSIONS: In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition. CI - (c) 2015 John Wiley & Sons Ltd. FAU - Fulcher, G AU - Fulcher G AD - The Royal North Shore Hospital and University of Sydney, Sydney, Australia. FAU - Matthews, D R AU - Matthews DR AD - Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK. FAU - Perkovic, V AU - Perkovic V AD - The George Institute for Global Health, The Royal Prince Alfred Hospital, and University of Sydney, Sydney, Australia. FAU - de Zeeuw, D AU - de Zeeuw D AD - Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands. FAU - Mahaffey, K W AU - Mahaffey KW AD - Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. FAU - Mathieu, C AU - Mathieu C AD - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium. FAU - Woo, V AU - Woo V AD - Endocrinology Section, Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada. FAU - Wysham, C AU - Wysham C AD - Washington State University, Spokane, WA, USA. FAU - Capuano, G AU - Capuano G AD - Janssen Research & Development, LLC, Raritan, NJ, USA. FAU - Desai, M AU - Desai M AD - Janssen Research & Development, LLC, Raritan, NJ, USA. FAU - Shaw, W AU - Shaw W AD - Janssen Research & Development, LLC, Raritan, NJ, USA. FAU - Vercruysse, F AU - Vercruysse F AD - Janssen Research & Development, Beerse, Belgium. FAU - Meininger, G AU - Meininger G AD - Janssen Research & Development, LLC, Raritan, NJ, USA. FAU - Neal, B AU - Neal B AD - The George Institute for Global Health, The Royal Prince Alfred Hospital, and University of Sydney, Sydney, Australia. CN - CANVAS trial collaborative group LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20151208 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (hemoglobin A1c protein, human) RN - 0SAC974Z85 (Canagliflozin) SB - IM MH - Aged MH - Biomimetics MH - Blood Pressure/drug effects MH - Canagliflozin/*administration & dosage MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/administration & dosage MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptide-1 Receptor/agonists MH - Glycated Hemoglobin/analysis/drug effects MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/*administration & dosage MH - Incretins/*administration & dosage MH - Male MH - Middle Aged MH - Sodium-Glucose Transporter 2 Inhibitors MH - Urologic Diseases/chemically induced/microbiology MH - Weight Loss/drug effects OTO - NOTNLM OT - canagliflozin OT - type 2 diabetes FIR - Arias, Pablo IR - Arias P FIR - Ulla, Maria Rosa IR - Ulla MR FIR - Alvarisqueta, Andres IR - Alvarisqueta A FIR - Maffei, Laura IR - Maffei L FIR - Fretes, Jose Osvaldo IR - Fretes JO FIR - De Lapertosa, Silvia Gorban IR - De Lapertosa SG FIR - Visco, Virginia IR - Visco V FIR - Sposetti, Georgina IR - Sposetti G FIR - Farias, Javier IR - Farias J FIR - Farias, Eduardo Francisco IR - Farias EF FIR - Cantero, Maria Cecilia IR - Cantero MC FIR - Feldman, Rodolfo IR - Feldman R FIR - Ridruejo, Maria Carolina IR - Ridruejo MC FIR - Calella, Pedro IR - Calella P FIR - Zaidman, Cesar IR - Zaidman C FIR - Stranks, Stephen IR - Stranks S FIR - Jeffries, William IR - Jeffries W FIR - Mah, Peak Man IR - Mah PM FIR - Macissac, Richard IR - Macissac R FIR - 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Solovyev, Oleg IR - Solovyev O FIR - Reshedko, Galina IR - Reshedko G FIR - Shilkina, Natalia IR - Shilkina N FIR - Chizhov, Petr IR - Chizhov P FIR - Shapovalova, Julia IR - Shapovalova J FIR - Sherenkov, Alexander IR - Sherenkov A FIR - Reshetko, Olga IR - Reshetko O FIR - Simanenkov, Vladimir IR - Simanenkov V FIR - Puig, Juan Garcia IR - Puig JG FIR - Saban, Jose IR - Saban J FIR - Pascual, Jose IR - Pascual J FIR - De Teresa, Luis IR - De Teresa L FIR - Dominguez, Jose IR - Dominguez J FIR - Delgado, Elias IR - Delgado E FIR - Calvo, Carlos IR - Calvo C FIR - Vida, Manuel IR - Vida M FIR - Duran, Santiago IR - Duran S FIR - Tinahones, Francisco IR - Tinahones F FIR - Salas, Jordi IR - Salas J FIR - Gonzalez, Jose Miguel IR - Gonzalez JM FIR - Monreal, Manuel IR - Monreal M FIR - Paz, Marco Antonio IR - Paz MA FIR - Nubiola, Andreu IR - Nubiola A FIR - Alvarez, Pere IR - Alvarez P FIR - Stenlof, Kaj IR - Stenlof K FIR - Koskinen, Pekka IR - Koskinen P FIR - Lindholm, Carl-Johan IR - Lindholm CJ FIR - Nilsson, Leif IR - Nilsson L FIR - Mathiesen, Ulrik IR - Mathiesen U FIR - Blom, Katarina Berndtsson IR - Blom KB FIR - Tengmark, Bengt-Olov IR - Tengmark BO FIR - Larsson, Kjell IR - Larsson K FIR - Jul-Nielsen, Hans IR - Jul-Nielsen H FIR - Norrby, Anders IR - Norrby A FIR - Larin, Oleksandr IR - Larin O FIR - Panina, Svetlana IR - Panina S FIR - Popik, Galyna IR - Popik G FIR - Kovalenko, Svitlana IR - Kovalenko S FIR - Voloshyna, Olena IR - Voloshyna O FIR - Tseluyko, Vera IR - Tseluyko V FIR - Gyrina, Olga IR - Gyrina O FIR - Vizir, Vadim IR - Vizir V FIR - Barna, Olga IR - Barna O FIR - Dolzhenko, Maryna IR - Dolzhenko M FIR - Ignatenko, Grigoriy IR - Ignatenko G FIR - Mostovoy, Yuriy IR - Mostovoy Y FIR - Korpachev, Vadim IR - Korpachev V FIR - Mankovskiy, Boris IR - Mankovskiy B FIR - Vatutin, Mykola IR - Vatutin M FIR - Akpunonu, Basil IR - Akpunonu B FIR - Zerikly, Rahfa IR - Zerikly R FIR - Baker, Claire IR - Baker C FIR - Wine, Alan IR - Wine A FIR - Kravitz, Alan IR - Kravitz A FIR - Bartilucci, Darlene IR - Bartilucci D FIR - Barzilay, Joshua IR - Barzilay J FIR - Breton, Christian IR - Breton C FIR - Buse, John IR - Buse J FIR - Cherlin, Richard IR - Cherlin R FIR - Cobble, Michael IR - Cobble M FIR - Ellis, Clarence IR - Ellis C FIR - Fink, Raymond IR - Fink R FIR - Forker, Alan IR - Forker A FIR - Garcia, Ronald IR - Garcia R FIR - Agarwal, Naresh IR - Agarwal N FIR - Hollander, Priscilla IR - Hollander P FIR - House, Angela IR - House A FIR - Huynh, Minh IR - Huynh M FIR - Ingebretsen, Richard IR - Ingebretsen R FIR - Jack, David IR - Jack D FIR - Kirstein, Judith IR - Kirstein J FIR - Lee, Ferrol IR - Lee F FIR - Lorber, Daniel IR - Lorber D FIR - McNeil, Donald IR - McNeil D FIR - Miers, Wendell IR - Miers W FIR - Murray, Alex IR - Murray A FIR - Call, Robert IR - Call R FIR - Ong, Stephen T IR - Ong ST FIR - Ovalle, Fernando IR - Ovalle F FIR - Pearlstein, Robert IR - Pearlstein R FIR - Piziak, Veronica IR - Piziak V FIR - Pomposini, Daniel IR - Pomposini D FIR - Robertson, David IR - Robertson D FIR - Rosenstock, Julio IR - Rosenstock J FIR - Schubart, Ulrich IR - Schubart U FIR - Shah, Shaukat IR - Shah S FIR - Stout, Rodney IR - Stout R FIR - Turner, Mark IR - Turner M FIR - Wallace, James IR - Wallace J FIR - Chuck, Leonard IR - Chuck L FIR - Weiss, Robert IR - Weiss R FIR - White, Judith IR - White J FIR - Wynne, Alan IR - Wynne A FIR - Wysham, Carol IR - Wysham C FIR - Alderman, Michael IR - Alderman M FIR - Crump, William IR - Crump W FIR - Pogue, Bryan IR - Pogue B FIR - Silva, Arnold IR - Silva A FIR - Guthrie, Roger IR - Guthrie R FIR - Lerman, Sam IR - Lerman S FIR - Madder, Robert IR - Madder R FIR - Janosz, Katherine Nori IR - Janosz KN FIR - Weiss, Daniel IR - Weiss D FIR - Kereiakes, Dean IR - Kereiakes D FIR - Graf, Ronald J IR - Graf RJ FIR - Rassouli, Negah IR - Rassouli N FIR - Muse, Derek IR - Muse D FIR - Kalen, Vicki IR - Kalen V FIR - Kersh, Robert IR - Kersh R FIR - Fernandez-Miro, Humberto IR - Fernandez-Miro H FIR - Dobrusin, Richard IR - Dobrusin R FIR - Johnson, Glover IR - Johnson G FIR - Bruce, Tami IR - Bruce T EDAT- 2015/10/10 06:00 MHDA- 2016/11/15 06:00 CRDT- 2015/10/10 06:00 PHST- 2015/07/15 00:00 [received] PHST- 2015/08/06 00:00 [revised] PHST- 2015/10/02 00:00 [accepted] PHST- 2015/10/10 06:00 [entrez] PHST- 2015/10/10 06:00 [pubmed] PHST- 2016/11/15 06:00 [medline] AID - 10.1111/dom.12589 [doi] PST - ppublish SO - Diabetes Obes Metab. 2016 Jan;18(1):82-91. doi: 10.1111/dom.12589. Epub 2015 Dec 8.