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Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER

Ahmed M. Shaman, Steve Bain Orcid Logo, George L. Bakris Orcid Logo, John B. Buse Orcid Logo, Thomas Idorn, Kenneth W. Mahaffey, Johannes F.E. Mann, Michael A. Nauck, Søren Rasmussen, Peter Rossing, Benjamin Wolthers, Bernard Zinman, Vlado Perkovic Orcid Logo

Circulation, Volume: 145, Issue: 8, Pages: 575 - 585

Swansea University Author: Steve Bain Orcid Logo

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DOI (Published version): 10.1161/circulationaha.121.055459

Abstract

We assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes (T2D). Pooled (N=12,637) and by-trial data from SUSTAIN 6 (N=3297) and LEADER (N=9340) were assessed for albuminuria change, annual slope of estimated glomerular filtration rate (eGFR)...

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Published in: Circulation
ISSN: 0009-7322 1524-4539
Published: Ovid Technologies (Wolters Kluwer Health) 2022
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Pooled (N=12,637) and by-trial data from SUSTAIN 6 (N=3297) and LEADER (N=9340) were assessed for albuminuria change, annual slope of estimated glomerular filtration rate (eGFR) change, and time to persistent eGFR reduction (30%, 40%, 50%, and 57%) from baseline. The median follow-up durations were 2.1 and 3.8 years for SUSTAIN 6 and LEADER, respectively. In the pooled analysis, semaglutide/liraglutide lowered albuminuria from baseline to 2 years post-randomization by 24% versus placebo (95% confidence interval [CI] [20%,27% ], &lt;0.001). Significant reductions were also observed in by-trial data analyses ( &lt;0.001 for all), the largest being with semaglutide 1.0 mg: 33% (95% CI [24%,40% ], &lt;0.001) at 2 years. With semaglutide 1.0 mg and liraglutide, eGFR slope decline was significantly slowed by 0.87 and 0.26 mL/min/1.73 m /year ( &lt;0.0001 and &lt;0.001), respectively, versus placebo. Effects appeared larger in those with baseline eGFR &lt;60 versus &#x2265;60 mL/min/1.73m ( =0.06 and 0.008 for semaglutide 1.0 mg and liraglutide, respectively). Semaglutide/liraglutide significantly lowered risk of persistent 40% and 50% eGFR reductions versus placebo (hazard ratio [HR] 0.86, 95% CI [0.75,0.99], =0.039, and HR 0.80, 95% CI [0.66,0.97], =0.023, respectively). Similar, non-significant, directional results were observed for 30% and 57% eGFR reductions (HR 0.92, 95% CI [0.84, 1.02], =0.10, and HR 0.89, 95% CI [0.69, 1.13], =0.34). In those with baseline eGFR 30-&lt;60mL/min/1.73m , the likelihood of persistent reduction for all thresholds was increased, ranging from a HR 0.71 for 30% reduction (95% CI [0.59,0.85], =0.0003, pinteraction=0.017) to 0.54 for 57% reduction (95% CI [0.36,0.81], =0.003, pinteraction=0.035). 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spelling 2022-12-09T10:57:59.3250912 v2 59068 2022-01-04 Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER 5399f4c6e6a70f3608a084ddb938511a 0000-0001-8519-4964 Steve Bain Steve Bain true false 2022-01-04 BMS We assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes (T2D). Pooled (N=12,637) and by-trial data from SUSTAIN 6 (N=3297) and LEADER (N=9340) were assessed for albuminuria change, annual slope of estimated glomerular filtration rate (eGFR) change, and time to persistent eGFR reduction (30%, 40%, 50%, and 57%) from baseline. The median follow-up durations were 2.1 and 3.8 years for SUSTAIN 6 and LEADER, respectively. In the pooled analysis, semaglutide/liraglutide lowered albuminuria from baseline to 2 years post-randomization by 24% versus placebo (95% confidence interval [CI] [20%,27% ], <0.001). Significant reductions were also observed in by-trial data analyses ( <0.001 for all), the largest being with semaglutide 1.0 mg: 33% (95% CI [24%,40% ], <0.001) at 2 years. With semaglutide 1.0 mg and liraglutide, eGFR slope decline was significantly slowed by 0.87 and 0.26 mL/min/1.73 m /year ( <0.0001 and <0.001), respectively, versus placebo. Effects appeared larger in those with baseline eGFR <60 versus ≥60 mL/min/1.73m ( =0.06 and 0.008 for semaglutide 1.0 mg and liraglutide, respectively). Semaglutide/liraglutide significantly lowered risk of persistent 40% and 50% eGFR reductions versus placebo (hazard ratio [HR] 0.86, 95% CI [0.75,0.99], =0.039, and HR 0.80, 95% CI [0.66,0.97], =0.023, respectively). Similar, non-significant, directional results were observed for 30% and 57% eGFR reductions (HR 0.92, 95% CI [0.84, 1.02], =0.10, and HR 0.89, 95% CI [0.69, 1.13], =0.34). In those with baseline eGFR 30-<60mL/min/1.73m , the likelihood of persistent reduction for all thresholds was increased, ranging from a HR 0.71 for 30% reduction (95% CI [0.59,0.85], =0.0003, pinteraction=0.017) to 0.54 for 57% reduction (95% CI [0.36,0.81], =0.003, pinteraction=0.035). In patients with T2D, semaglutide/liraglutide offered kidney-protective effects, which appeared more pronounced in those with pre-existing chronic kidney disease. Journal Article Circulation 145 8 575 585 Ovid Technologies (Wolters Kluwer Health) 0009-7322 1524-4539 albuminuria; chronic kidney disease; eGFR; glucagon-like peptide-1 receptor agonists; liraglutide; semaglutide; type 2 diabetes 22 2 2022 2022-02-22 10.1161/circulationaha.121.055459 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Other Novo Nordisk A/S 2022-12-09T10:57:59.3250912 2022-01-04T14:18:51.5185243 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Ahmed M. Shaman 1 Steve Bain 0000-0001-8519-4964 2 George L. Bakris 0000-0003-1183-1267 3 John B. Buse 0000-0002-9723-3876 4 Thomas Idorn 5 Kenneth W. Mahaffey 6 Johannes F.E. Mann 7 Michael A. Nauck 8 Søren Rasmussen 9 Peter Rossing 10 Benjamin Wolthers 11 Bernard Zinman 12 Vlado Perkovic 0000-0002-4257-7620 13 59068__22586__ec5aaf3a5b254ad2b3148ab4a31f6896.pdf 59068.pdf 2022-03-14T12:30:28.0213755 Output 1552147 application/pdf Version of Record true © 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution License true eng https://creativecommons.org/licenses/by/4.0/
title Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER
spellingShingle Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER
Steve Bain
title_short Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER
title_full Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER
title_fullStr Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER
title_full_unstemmed Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER
title_sort Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER
author_id_str_mv 5399f4c6e6a70f3608a084ddb938511a
author_id_fullname_str_mv 5399f4c6e6a70f3608a084ddb938511a_***_Steve Bain
author Steve Bain
author2 Ahmed M. Shaman
Steve Bain
George L. Bakris
John B. Buse
Thomas Idorn
Kenneth W. Mahaffey
Johannes F.E. Mann
Michael A. Nauck
Søren Rasmussen
Peter Rossing
Benjamin Wolthers
Bernard Zinman
Vlado Perkovic
format Journal article
container_title Circulation
container_volume 145
container_issue 8
container_start_page 575
publishDate 2022
institution Swansea University
issn 0009-7322
1524-4539
doi_str_mv 10.1161/circulationaha.121.055459
publisher Ovid Technologies (Wolters Kluwer Health)
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description We assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes (T2D). Pooled (N=12,637) and by-trial data from SUSTAIN 6 (N=3297) and LEADER (N=9340) were assessed for albuminuria change, annual slope of estimated glomerular filtration rate (eGFR) change, and time to persistent eGFR reduction (30%, 40%, 50%, and 57%) from baseline. The median follow-up durations were 2.1 and 3.8 years for SUSTAIN 6 and LEADER, respectively. In the pooled analysis, semaglutide/liraglutide lowered albuminuria from baseline to 2 years post-randomization by 24% versus placebo (95% confidence interval [CI] [20%,27% ], <0.001). Significant reductions were also observed in by-trial data analyses ( <0.001 for all), the largest being with semaglutide 1.0 mg: 33% (95% CI [24%,40% ], <0.001) at 2 years. With semaglutide 1.0 mg and liraglutide, eGFR slope decline was significantly slowed by 0.87 and 0.26 mL/min/1.73 m /year ( <0.0001 and <0.001), respectively, versus placebo. Effects appeared larger in those with baseline eGFR <60 versus ≥60 mL/min/1.73m ( =0.06 and 0.008 for semaglutide 1.0 mg and liraglutide, respectively). Semaglutide/liraglutide significantly lowered risk of persistent 40% and 50% eGFR reductions versus placebo (hazard ratio [HR] 0.86, 95% CI [0.75,0.99], =0.039, and HR 0.80, 95% CI [0.66,0.97], =0.023, respectively). Similar, non-significant, directional results were observed for 30% and 57% eGFR reductions (HR 0.92, 95% CI [0.84, 1.02], =0.10, and HR 0.89, 95% CI [0.69, 1.13], =0.34). In those with baseline eGFR 30-<60mL/min/1.73m , the likelihood of persistent reduction for all thresholds was increased, ranging from a HR 0.71 for 30% reduction (95% CI [0.59,0.85], =0.0003, pinteraction=0.017) to 0.54 for 57% reduction (95% CI [0.36,0.81], =0.003, pinteraction=0.035). In patients with T2D, semaglutide/liraglutide offered kidney-protective effects, which appeared more pronounced in those with pre-existing chronic kidney disease.
published_date 2022-02-22T04:16:05Z
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