瑞他鲁肽对2型糖尿病和/或肥胖症参与者肾脏参数的影响。
The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity.
作者信息
Heerspink Hiddo J L, Lu Zeqing, Du Yu, Duffin Kevin L, Coskun Tamer, Haupt Axel, Hartman Mark L
机构信息
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
出版信息
Kidney Int Rep. 2025 Apr 2;10(6):1980-1992. doi: 10.1016/j.ekir.2025.03.049. eCollection 2025 Jun.
INTRODUCTION
Obesity and type 2 diabetes mellitus (T2D) increase the risk of kidney disease. This study assessed changes in kidney parameters with retatrutide, an agonist of the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors.
METHODS
A analysis of 2 retatrutide studies (dose range: 0.5-12 mg) was performed in participants (estimated glomerular filtration rate [eGFR] ≥ 45 ml/min per 1.73 m) with T2D ( = 281) and with overweight or obesity without T2D ( = 338). Both studies were placebo-controlled; the T2D study included dulaglutide 1.5 mg as an active comparator. We assessed change from baseline at week 36 (T2D) and week 48 (overweight/obesity) in urine albumin-to-creatinine ratio (UACR) and eGFR derived from creatinine, cystatin C, or both.
RESULTS
At baseline, mean eGFR derived from creatinine and median UACR were 91 ml/min per 1.73 m and 13 mg/g, respectively in the T2D study, and 90 ml/min per 1.73 m and 7 mg/g, respectively in the obesity study. In participants with T2D, retatrutide 12 mg was associated with reduced UACR compared with placebo at 36 weeks by -37.0% (95% CI: -57.3 to -7.0); eGFR was unchanged compared with placebo. In participants with overweight or obesity, retatrutide 8 mg and 12 mg, compared with placebo at 48 weeks, was associated with decreased UACR by -28.0% (95% CI: -46.0 to -4.1) and -31.5% (95% CI: -49.3 to -7.4), respectively, and with increased eGFR derived from creatinine by 5.3 ml/min per 1.73 m (95% CI: 1.9-8.7) and 8.5 ml/min per 1.73 m (95% CI: 4.9-12.1), respectively. Similar increases in eGFR derived from cystatin C and combined creatinine-cystatin C eGFR were observed. Because most patients had normal albuminuria, the absolute reduction in UACR was modest.
CONCLUSION
Higher doses of retatrutide were associated with reduced UACR in participants with T2D and obesity, and with increased eGFR in participants with obesity but not in those with T2D.
引言
肥胖和2型糖尿病（T2D）会增加患肾病的风险。本研究评估了retatrutide（一种葡萄糖依赖性促胰岛素多肽（GIP）、胰高血糖素样肽-1（GLP-1）和胰高血糖素受体激动剂）对肾脏参数的影响。
方法
对两项retatrutide研究（剂量范围：0.5 - 12 mg）进行分析，参与者为患有T2D（n = 281）且估算肾小球滤过率（eGFR）≥45 ml/min per 1.73 m²的患者，以及超重或肥胖但无T2D（n = 338）的患者。两项研究均为安慰剂对照；T2D研究中纳入度拉糖肽1.5 mg作为活性对照。我们评估了在第36周（T2D）和第48周（超重/肥胖）时，尿白蛋白与肌酐比值（UACR）以及由肌酐、胱抑素C或两者得出的eGFR相对于基线的变化。
结果
在基线时，T2D研究中由肌酐得出的平均eGFR和UACR中位数分别为91 ml/min per 1.73 m²和13 mg/g，肥胖研究中分别为90 ml/min per 1.73 m²和7 mg/g。在患有T2D的参与者中，36周时，与安慰剂相比，12 mg的retatrutide使UACR降低了37.0%（95% CI：-57.3至-7.0）；与安慰剂相比，eGFR未发生变化。在超重或肥胖的参与者中，48周时，与安慰剂相比，8 mg和12 mg的retatrutide分别使UACR降低了28.0%（95% CI：-46.0至-4.1）和31.5%（95% CI：-49.3至-7.4），并且由肌酐得出的eGFR分别增加了5.3 ml/min per 1.73 m²（95% CI：1.9 - 8.7）和8.5 ml/min per 1.73 m²（95% CI：4.9 - 12.1）。观察到由胱抑素C得出的eGFR以及联合肌酐 - 胱抑素C得出的eGFR也有类似增加。由于大多数患者蛋白尿正常，UACR的绝对降低幅度较小。
结论
较高剂量的retatrutide与T2D和肥胖参与者的UACR降低相关，与肥胖参与者的eGFR增加相关，但与T2D参与者的eGFR增加无关。
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