# 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

Article · Shaman AM, Bain SC, Bakris GL, Buse JB, Idorn T, Mahaffey KW, Mann JFE, Nauck MA, Rasmussen S, Rossing P, Wolthers B, Zinman B, Perkovic V

- Archive id: doi:10.1161/circulationaha.121.055459
- Published: 2021-12-14
- Venue: Circulation
- DOI: https://doi.org/10.1161/circulationaha.121.055459
- PMID: 34903039
- PMCID: PMC8860212
- Citations: 209
- Source URL: https://doi.org/10.1161/circulationaha.121.055459
- PDF: https://europepmc.org/articles/PMC8860212/pdf
- Provenance: europepmc

## Abstract

Background We assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes. Methods Pooled (n=12 637) and by-trial data from SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes; n=3297) and LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; 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. Results The median follow-up durations were 2.1 years for SUSTAIN 6 and 3.8 years for LEADER. In the pooled analysis, semaglutide/liraglutide lowered albuminuria from baseline to 2 years after randomization by 24% versus placebo (95% CI, 20%-27%; P \<0.001). Significant reductions were also observed in by-trial data analyses ( P \<0.001 for all), the largest being with semaglutide 1.0 mg (33% \[95% CI, 24%-40%\]; P \<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 2 /y ( P \<0.0001 and P \<0.001), respectively, versus placebo. Effects appeared larger in patients with baseline eGFR \<60 versus ≥60 mL/min/1.73 m 2 ( P interaction =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 \[95% CI, 0.75-0.99\]; P =0.039 and HR, 0.80 \[95% CI, 0.66-0.97\]; P =0.023, respectively). Similar, nonsignificant, directional results were observed for 30% and 57% eGFR reductions (HR, 0.92 \[95% CI, 0.84-1.02\]; P =0.10 and HR, 0.89 \[95% CI, 0.69-1.13\]; P =0.34). In patients with baseline eGFR 30 to \<60 mL/min/1.73 m 2 , the likelihood of persistent reduction for all thresholds was increased, ranging from HR 0.71 for 30% reduction (95% CI, 0.59-0.85; P =0.0003, P interaction =0.017) to 0.54 for 57% reduction (95% CI, 0.36-0.81; P =0.003, P interaction =0.035). Conclusions In patients with type 2 diabetes, semaglutide/liraglutide offered kidney-protective effects, which appeared more pronounced in patients with preexisting chronic kidney disease.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [GLP-1 & Incretin Therapies](https://space-kitty.com/topics/glp1-metabolic)

---
Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.