Semaglutide may offer renoprotection in type 2 diabetes
medwireNews: Semaglutide has the potential to improve kidney outcomes in people with type 2 diabetes, a post-hoc analysis of the SUSTAIN 1–7 trials shows.
Across the trials, “semaglutide was associated with initial reductions in eGFR [estimated glomerular filtration rate] that plateaued, and marked reductions in UACR [urinary albumin-to-creatinine ratio],” report Johannes Mann (KfH Kidney Center, Munich, Germany) and co-authors in The Lancet Diabetes & Endocrinology.
They add: “Reductions in UACR have been associated with improved kidney outcomes, such as a reduced risk of end-stage kidney disease.”
The analysis included pooled data for 8416 patients with type 2 diabetes enrolled in the SUSTAIN 1–5 and SUSTAIN 7 randomized controlled trials, and the SUSTAIN 6 cardiovascular outcomes trial.
The researchers found that in SUSTAIN 1–5 and SUSTAIN 7, eGFR decreased by a greater degree with semaglutide than with placebo from baseline to week 12, with estimated treatment differences (ETDs) of 2.2 mL/min per 1.73 m2 and 3.0 mL/min per 1.73 m2 in the semaglutide 0.5 mg and 1.0 mg groups, respectively.
However, between weeks 12 and 30, eGFR stabilized, with no further reductions in the active treatment groups and a slight reduction (0.2 mL/min per 1.73 m2) with placebo.
In SUSTAIN 6, which had a longer follow-up, a similar pattern was seen during the early treatment period (weeks 0–16), with ETDs of 1.29 mL/min per 1.73 m2 and 1.56 mL/min per 1.73 m2 with semaglutide 0.5 mg and 1.0 mg, respectively, versus placebo. However, between weeks 16 and 104, there was a greater eGFR decline with placebo than with semaglutide, meaning that by the end of treatment the ETDs were 0.07 mL/min per 1.73 m2 and 0.97 mL/min per 1.73 m2 with semaglutide 0.5 mg and 1.0 mg, respectively.
When the team analyzed the data according to baseline eGFR, they found that the initial eGFR decline was greater among individuals with normal or mildly impaired kidney function than among those with moderate or severely impaired function.
For UACR, Mann and team observed reductions across the SUSTAIN 1–6 trials among the patients who received semaglutide treatment and increases for those who received placebo.
This resulted in estimated treatment ratios of 0.74 and 0.68 for semaglutide 0.5 mg and 1.0 mg versus placebo in the SUSTAIN 1–5 trials, and 0.75 and 0.66, respectively, in the SUSTAIN 6 trial.
And analyses by baseline albuminuria indicated that the effects were greatest among patients with microalbuminuria or macroalbuminuria. Indeed, there were no changes in UACR among patients with normoalbuminuria at baseline, the researchers note.
Mann et al also point out that “there was no imbalance in the incidence of adverse events relating to acute kidney failure or kidney and urinary disorders between semaglutide and comparators; therefore, the initial eGFR decline does not seem to be related to overall on-treatment kidney adverse events or acute kidney injury.”
The authors conclude that, taken together, their findings suggest ”that semaglutide has a suitable kidney safety profile and has potentially nephroprotective effects.”
In an accompanying comment, Srikanth Bellary (Aston University, Birmingham, UK) and co-authors describe the findings as “highly relevant in the context of management of type 2 diabetes and specifically in the prevention and progression of associated diabetic kidney disease.”
They stress, however, that “important questions remain” particularly regarding the long-term renoprotective benefits of semaglutide. They hope however, ongoing studies, such as FLOW, will answer some of these questions.
The study findings were also presented at the virtual 56th EASD Annual Meeting.
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