Providence Health Care, University of Washington, Spokane, Washington, USA.
Novo Nordisk A/S, Medical & Science, Søborg, Denmark.
Kidney Int. 2023 Apr;103(4):772-781. doi: 10.1016/j.kint.2022.12.028. Epub 2023 Feb 2.
Glucagon-like peptide-1 receptor agonists reduce albuminuria and may stabilize the estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (T2D). In this post hoc analysis of the SUSTAIN 6/PIONEER 6 trials encompassing 6480 participants at high cardiovascular risk (semaglutide, 3239 participants; placebo, 3241 participants), we investigated the effects of semaglutide versus placebo on eGFR decline. Pooled data by treatment were evaluated for annual eGFR change (total annual eGFR slope in ml/min per 1.73 m) from baseline to end of treatment and time to persistent eGFR reductions of 30%, 40%, 50% and 57% or more, including subgroup analyses by baseline eGFR (30 to under 60 or 60 and over ml/min per 1.73 m). In the overall population, the estimated treatment difference (ETD; semaglutide versus placebo) in annual eGFR slope was significant at 0.59 ml/min per 1.73 m (95% confidence interval 0.29; 0.89). The ETD was numerically largest in the 30 to under 60 ml/min per 1.73 m eGFR subgroup, 1.06 ml/min per 1.73 m (0.45; 1.67), but no significant interaction was observed for treatment effect by subgroup. Hazard ratios (semaglutide versus placebo) for time to persistent eGFR decline were under 1.0 for all eGFR thresholds in the overall population; and were numerically lower in the baseline eGFR 30 to under 60 ml/min per 1.73 m subgroup versus the overall population, although no significant interaction was observed for treatment effect by subgroup. Thus, pooled analyses of clinical trial data in patients with T2D suggest that semaglutide may reduce the rate of eGFR decline.
胰高血糖素样肽-1 受体激动剂可减少白蛋白尿，并可能稳定 2 型糖尿病（T2D）患者的估算肾小球滤过率（eGFR）。在 SUSTAIN 6/PIONEER 6 试验的事后分析中，该试验共纳入了 6480 名心血管高危患者（司美格鲁肽组 3239 例，安慰剂组 3241 例），我们研究了司美格鲁肽与安慰剂对 eGFR 下降的影响。根据治疗情况对汇总数据进行评估，以了解从基线到治疗结束时 eGFR 的年变化（1.73 m 每毫升每分钟总 eGFR 斜率），并评估 eGFR 持续下降 30%、40%、50%和 57%或更多的时间，包括根据基线 eGFR（30 至低于 60 或 60 及以上 ml/min/1.73 m）的亚组分析。在总体人群中，eGFR 斜率的估计治疗差异（ETD；司美格鲁肽与安慰剂）为 0.59 ml/min/1.73 m（95%置信区间 0.29；0.89），差异有统计学意义。在 eGFR 为 30 至低于 60 ml/min/1.73 m 的亚组中，ETD 最大为 1.06 ml/min/1.73 m（0.45；1.67），但未观察到治疗效果的亚组间存在显著交互作用。在总体人群中，所有 eGFR 阈值的持续 eGFR 下降时间的风险比（司美格鲁肽与安慰剂）均低于 1.0；在 eGFR 基线为 30 至低于 60 ml/min/1.73 m 的亚组中，数值低于总体人群，尽管未观察到治疗效果的亚组间存在显著交互作用。因此，在 T2D 患者的临床试验数据汇总分析中，司美格鲁肽可能会降低 eGFR 下降的速度。
