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

Abstract

Background: We assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes (T2D). Methods: 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. Results: 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% ], 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 /year ( p <0.0001 and p <0.001), respectively, versus placebo. Effects appeared larger in those with baseline eGFR <60 versus ≥60 mL/min/1.73m 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, non-significant, 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 those with baseline eGFR 30−<60mL/min/1.73m 2 , 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], p =0.0003, pinteraction=0.017) to 0.54 for 57% reduction (95% CI [0.36,0.81], p =0.003, pinteraction=0.035). Conclusions: In patients with T2D, semaglutide/liraglutide offered kidney-protective effects, which appeared more pronounced in those with pre-existing chronic kidney disease.