GLP-1 receptor agonists may offer kidney protection in patients with type 2 diabetes
An industry-conducted pooled analysis of two large trials of glucagon-like peptide-1 (GLP-1) receptor agonists found that both semaglutide and liraglutide slowed kidney function decline, with semaglutide appearing to have the greatest effect.
Semaglutide and liraglutide offered renal-protective effects, which appeared more pronounced in those with pre-existing chronic kidney disease, a study found.
Researchers pooled data from two trials, SUSTAIN 6 (n=3,297) and LEADER (n=9,340), that compared once-weekly semaglutide and once-daily liraglutide, respectively, to placebo, to evaluate changes in albuminuria, annual slope of estimated glomerular filtration rate (eGFR) change, time to persistent proportional eGFR reductions of 40% and 50% from baseline, and a composite endpoint of time from randomization to first occurrence of kidney failure/death or proportional eGFR decline. The study's funder, Novo Nordisk A/S, participated in the study design and in management, analysis, and interpretation of the data, and three of the 13 study authors are Novo Nordisk A/S employees. Results were published Dec. 14 by Circulation.
The median follow-up durations were 2.1 and 3.8 years for SUSTAIN 6 and LEADER, respectively. In the pooled analysis, semaglutide and liraglutide lowered albuminuria from baseline to two years postrandomization by 24% versus placebo (95% CI, 20% to 27%; P<0.001). Significant reductions were also observed in by-trial data analyses (P<0.001 for all comparisons), with the largest for semaglutide, 1.0 mg, at 33% (95% CI, 24% to 40%, P<0.001) at two years.
Compared to placebo, semaglutide, 1.0 mg, and liraglutide slowed eGFR slope decline significantly by 0.87 and 0.26 mL/min/1.73 m2 per year (P<0.0001 and P<0.001), respectively. Effects appeared larger in patients with a baseline eGFR less than 60 mL/min/1.73 m2. Compared to placebo, semaglutide and liraglutide significantly lowered risk of persistent 40% and 50% eGFR reductions (hazard ratios [HR], 0.86 [95% CI, 0.75 to 0.99] [P=0.039] and 0.80 [95% CI, 0.66 to 0.97] [P=0.023], respectively). Similar although not statistically significant results were observed for 30% and 57% eGFR reductions.
The study authors noted that the study was an exploratory analysis, and that the two trials were not originally powered to evaluate kidney outcomes, included patients with relatively low kidney risk at baseline, and did not account for terminal events such as cardiovascular death.
Still, the larger magnitude of effect of semaglutide, 1.0 mg, on both albuminuria and eGFR compared with semaglutide, 0.5 mg, and liraglutide suggests that it might have an important role in protecting kidney function in diabetes, the researchers noted.
“This may be especially relevant in people with existing [diabetic kidney disease],” the authors wrote. “Although these post hoc analyses of secondary outcomes are promising, a specific, sufficiently powered trial aiming to assess the effects of semaglutide/liraglutide on kidney outcomes in people with diabetes and kidney disease is needed and currently ongoing.”