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, Stephen C. Bain, George L. Bakris, John B. Buse, Thomas Idorn, Kenneth W. Mahaffey, Johannes F.E. Mann, Michael A. Nauck, Søren Rasmussen, Peter Rossing, Benjamin Ole Wolthers, Bernard Zinman, Vlado Perkovic
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.