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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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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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URI: https://cronfa.swan.ac.uk/Record/cronfa59068
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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) 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.
Keywords: albuminuria; chronic kidney disease; eGFR; glucagon-like peptide-1 receptor agonists; liraglutide; semaglutide; type 2 diabetes
College: Swansea University Medical School
Funders: Novo Nordisk A/S
Issue: 8
Start Page: 575
End Page: 585