Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering
Introduction Relationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain.Research design and methods We analyzed 4395 individuals with prebaseline and postbaseline hemoglobin A1c (HbA1c) randomized to ca...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-05-01
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| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/11/3/e003270.full |
| _version_ | 1797772111519940608 |
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| author | Bernard Zinman Bruce Neal George L Bakris Vlado Perkovic Meg J Jardine Kris Rogers Jie Yu Adeera Levin Dick de Zeeuw Hong Zhang Kenneth W Mahaffey Clare Arnott Rajiv Agarwal Gian Luca Di Tanna Carol Pollock David C Wheeler Christopher P Cannon David M Charytan Hiddo J Lambers Heerspink Norman Rosenthal |
| author_facet | Bernard Zinman Bruce Neal George L Bakris Vlado Perkovic Meg J Jardine Kris Rogers Jie Yu Adeera Levin Dick de Zeeuw Hong Zhang Kenneth W Mahaffey Clare Arnott Rajiv Agarwal Gian Luca Di Tanna Carol Pollock David C Wheeler Christopher P Cannon David M Charytan Hiddo J Lambers Heerspink Norman Rosenthal |
| author_sort | Bernard Zinman |
| collection | DOAJ |
| description | Introduction Relationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain.Research design and methods We analyzed 4395 individuals with prebaseline and postbaseline hemoglobin A1c (HbA1c) randomized to canagliflozin (n=2193) or placebo (n=2202) in The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects on HbA1c were assessed using mixed models. Mediation of treatment effects by achieved glycemic control was analyzed using proportional hazards regression with and without adjustment for achieved HbA1c. End points included combined kidney or cardiovascular death, end-stage kidney disease or doubling of serum creatinine (primary trial outcome), and individual end point components.Results HbA1c lowering was modified by baseline estimated glomerular filtration rate (eGFR). For baseline eGFR 60–90, 45–59, and 30–44 mL/min/1.73 m2, overall HbA1c (canagliflozin vs placebo) decreased by −0.24%, −0.14%, and −0.08% respectively and likelihood of >0.5% decrease in HbA1c decreased with ORs of 1.47 (95% CI 1.27 to 1.67), 1.12 (0.94 to 1.33) and 0.99 (0.83 to 1.18), respectively. Adjustment for postbaseline HbA1c marginally attenuated canagliflozin effects on primary and kidney composite outcomes: unadjusted HR 0.67 (95% CI 0.57 to 0.80) and 0.66 (95% CI 0.53 to 0.81); adjusted for week 13 HbA1c, HR 0.71 (95% CI 0.060 to 0.84) and 0.68 (95% CI 0.55 to 0.83). Results adjusted for time-varying HbA1c or HbA1c as a cubic spline were similar and consistent with preserved clinical benefits across a range of excellent and poor glycemic control.Conclusions The glycemic effects of canagliflozin are attenuated at lower eGFR but effects on kidney and cardiac end points are preserved. Non-glycemic effects may be primarily responsible for the kidney and cardioprotective benefits of canagliflozin.22 |
| first_indexed | 2024-03-12T21:47:21Z |
| format | Article |
| id | doaj.art-83663dfd99b5429482efb801e4aa82d8 |
| institution | Directory Open Access Journal |
| issn | 2052-4897 |
| language | English |
| last_indexed | 2024-03-12T21:47:21Z |
| publishDate | 2023-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj.art-83663dfd99b5429482efb801e4aa82d82023-07-26T10:20:07ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972023-05-0111310.1136/bmjdrc-2022-003270Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose loweringBernard Zinman0Bruce Neal1George L Bakris2Vlado Perkovic3Meg J Jardine4Kris Rogers5Jie Yu6Adeera Levin7Dick de Zeeuw8Hong Zhang9Kenneth W Mahaffey10Clare Arnott11Rajiv Agarwal12Gian Luca Di Tanna13Carol Pollock14David C Wheeler15Christopher P Cannon16David M Charytan17Hiddo J Lambers Heerspink18Norman Rosenthal19University of Toronto, Toronto, Ontario, Canada3 The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, AustraliaUChicago Medicine, Chicago, Illinois, USAGeorge Institute for Global Health, Sydney, New South Wales, AustraliaThe University of Sydney, Sydney, New South Wales, AustraliaGeorge Institute for Global Health, Sydney, New South Wales, AustraliaGeorge Institute for Global Health, Sydney, New South Wales, AustraliaNephrology, St. Paul`s Hospital, Newtown, New South Wales, AustraliaClinical Pharmacology, University Medical Center Groningen, Groningen, The NetherlandsRenal Division of Peking University First Hospital, Beijing, ChinaDepartment of Medicine, Stanford University School of Medicine, Stanford, California, USAThe George Institute for Global Health, Newtown, New South Wales, AustraliaVA Medical Center, Bedford, Massachusetts, USAGeorge Institute for Global Health, Sydney, New South Wales, AustraliaMedicine, The University of Sydney, Sydney, New South Wales, AustraliaDepartment of Renal Medicine, UCL, London, UKBaim Institute for Clinical Research, Boston, Massachusetts, USAUnited States, NYU, New York, New York, USAChildren`s Hospital of Philadelphia, Philadelphia, Pennsylvania, USAJanssen Research & Development LLC, Raritan, New Jersey, USAIntroduction Relationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain.Research design and methods We analyzed 4395 individuals with prebaseline and postbaseline hemoglobin A1c (HbA1c) randomized to canagliflozin (n=2193) or placebo (n=2202) in The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects on HbA1c were assessed using mixed models. Mediation of treatment effects by achieved glycemic control was analyzed using proportional hazards regression with and without adjustment for achieved HbA1c. End points included combined kidney or cardiovascular death, end-stage kidney disease or doubling of serum creatinine (primary trial outcome), and individual end point components.Results HbA1c lowering was modified by baseline estimated glomerular filtration rate (eGFR). For baseline eGFR 60–90, 45–59, and 30–44 mL/min/1.73 m2, overall HbA1c (canagliflozin vs placebo) decreased by −0.24%, −0.14%, and −0.08% respectively and likelihood of >0.5% decrease in HbA1c decreased with ORs of 1.47 (95% CI 1.27 to 1.67), 1.12 (0.94 to 1.33) and 0.99 (0.83 to 1.18), respectively. Adjustment for postbaseline HbA1c marginally attenuated canagliflozin effects on primary and kidney composite outcomes: unadjusted HR 0.67 (95% CI 0.57 to 0.80) and 0.66 (95% CI 0.53 to 0.81); adjusted for week 13 HbA1c, HR 0.71 (95% CI 0.060 to 0.84) and 0.68 (95% CI 0.55 to 0.83). Results adjusted for time-varying HbA1c or HbA1c as a cubic spline were similar and consistent with preserved clinical benefits across a range of excellent and poor glycemic control.Conclusions The glycemic effects of canagliflozin are attenuated at lower eGFR but effects on kidney and cardiac end points are preserved. Non-glycemic effects may be primarily responsible for the kidney and cardioprotective benefits of canagliflozin.22https://drc.bmj.com/content/11/3/e003270.full |
| spellingShingle | Bernard Zinman Bruce Neal George L Bakris Vlado Perkovic Meg J Jardine Kris Rogers Jie Yu Adeera Levin Dick de Zeeuw Hong Zhang Kenneth W Mahaffey Clare Arnott Rajiv Agarwal Gian Luca Di Tanna Carol Pollock David C Wheeler Christopher P Cannon David M Charytan Hiddo J Lambers Heerspink Norman Rosenthal Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering BMJ Open Diabetes Research & Care |
| title | Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering |
| title_full | Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering |
| title_fullStr | Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering |
| title_full_unstemmed | Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering |
| title_short | Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering |
| title_sort | cardiorenal protective effects of canagliflozin in credence according to glucose lowering |
| url | https://drc.bmj.com/content/11/3/e003270.full |
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