Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.
Diabetes Research Centre, University of Leicester, Leicester, U.K.
Diabetes Care. 2023 Apr 1;46(4):801-810. doi: 10.2337/dc22-1889.
These post hoc analyses of the Semaglutide Treatment Effect in People with obesity (STEP) 1-3 trials (NCT03548935, NCT03552757, and NCT03611582) explored the effects of semaglutide (up to 2.4 mg) on kidney function.
STEP 1-3 included adults with overweight/obesity; STEP 2 patients also had type 2 diabetes. Participants received once-weekly subcutaneous semaglutide 1.0 mg (STEP 2 only), 2.4 mg, or placebo for 68 weeks, plus lifestyle intervention (STEP 1 and 2) or intensive behavioral therapy (STEP 3). Changes in urine albumin-to-creatinine ratio (UACR) and UACR status from baseline to week 68 were assessed for STEP 2. Changes in estimated glomerular filtration rate (eGFR) were assessed from pooled STEP 1-3 data.
In STEP 2, 1,205 (99.6% total cohort) patients had UACR data; geometric mean baseline UACR was 13.7, 12.5, and 13.2 mg/g with semaglutide 1.0 mg, 2.4 mg, and placebo, respectively. At week 68, UACR changes were -14.8% and -20.6% with semaglutide 1.0 mg and 2.4 mg, respectively, and +18.3% with placebo (between-group differences [95% CI] vs. placebo: -28.0% [-37.3, -17.3], P < 0.0001 for semaglutide 1.0 mg; -32.9% [-41.6, -23.0], P = 0.003 for semaglutide 2.4 mg). UACR status improved in greater proportions of patients with semaglutide 1.0 mg and 2.4 mg versus placebo (P = 0.0004 and P = 0.0014, respectively). In the pooled STEP 1-3 analyses, 3,379 participants had eGFR data; there was no difference between semaglutide 2.4 mg and placebo in eGFR trajectories at week 68.
Semaglutide improved UACR in adults with overweight/obesity and type 2 diabetes. In participants with normal kidney function, semaglutide did not have an effect on eGFR decline.
这些 Semaglutide 在肥胖人群中的治疗效果（STEP）1-3 试验（NCT03548935、NCT03552757 和 NCT03611582）的事后分析探讨了司美格鲁肽（高达 2.4mg）对肾功能的影响。
STEP 1-3 纳入了超重/肥胖的成年人；STEP 2 患者还患有 2 型糖尿病。参与者接受每周一次皮下注射司美格鲁肽 1.0mg（仅 STEP 2）、2.4mg 或安慰剂，持续 68 周，同时进行生活方式干预（STEP 1 和 2）或强化行为疗法（STEP 3）。评估 STEP 2 中基线至第 68 周时尿白蛋白与肌酐比值（UACR）的变化和 UACR 状态。从 STEP 1-3 的汇总数据评估估计肾小球滤过率（eGFR）的变化。
在 STEP 2 中，1205 名（总队列的 99.6%）患者有 UACR 数据；司美格鲁肽 1.0mg、2.4mg 和安慰剂组的基线 UACR 几何均数分别为 13.7、12.5 和 13.2mg/g。在第 68 周时，司美格鲁肽 1.0mg 和 2.4mg 组 UACR 变化分别为-14.8%和-20.6%，安慰剂组为+18.3%（与安慰剂相比，组间差异[95%CI]：-28.0%[-37.3，-17.3]，P<0.0001 用于司美格鲁肽 1.0mg；-32.9%[-41.6，-23.0]，P=0.003 用于司美格鲁肽 2.4mg）。与安慰剂相比，更多的司美格鲁肽 1.0mg 和 2.4mg 组患者 UACR 状态得到改善（P=0.0004 和 P=0.0014）。在 STEP 1-3 的汇总分析中，3379 名参与者有 eGFR 数据；在第 68 周时，司美格鲁肽 2.4mg 和安慰剂组之间的 eGFR 轨迹没有差异。
司美格鲁肽可改善超重/肥胖和 2 型糖尿病成人的 UACR。在肾功能正常的参与者中，司美格鲁肽对 eGFR 下降没有影响。
