de Vries Sieta T, Pena Michelle J, Tye Sok Cin, Peters Sanne A E, van Raalte Daniël H, Arnott Clare, Voors Adriaan A, Mol Peter G M, Denig Petra, Heerspink Hiddo J L
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Diabetologia. 2025 Mar;68(3):507-515. doi: 10.1007/s00125-024-06325-y. Epub 2024 Dec 10.
AIMS/HYPOTHESIS: Our aim was to assess sex differences in the efficacy of angiotensin receptor blockers (i.e. losartan and irbesartan) on kidney and cardiovascular outcomes in individuals with type 2 diabetes and diabetic kidney disease.
Data from the Angiotensin II Antagonist Losartan Study (RENAAL) and Irbesartan type II Diabetic Nephropathy Trial (IDNT) were used. The kidney outcome was time to first event of end-stage kidney disease or doubling of serum creatinine. The cardiovascular outcome was time to first event of a composite of stroke, myocardial infarction, cardiovascular death or hospitalisation for heart failure. Sex differences were assessed by a sex × treatment interaction term in Cox proportional hazards models.
Included were 1737 male participants and 924 female participants. The beneficial effect of angiotensin receptor blockers on the kidney outcome was similar between male and female participants (HR in male participants 0.72 [95% CI 0.59, 0.86] vs HR in female participants 0.86 [95% CI 0.69, 1.06]; sex × treatment interaction HR 1.19 [95% CI 0.89, 1.59]). For the cardiovascular outcome, angiotensin receptor blockers lowered the risk in male but not in female participants (HR in male participants 0.81 [95% CI 0.69, 0.95] vs HR in female participants 1.11 [95% CI 0.88, 1.40]; sex × treatment interaction HR 1.37 [95% CI 1.03, 1.82]).
CONCLUSIONS/INTERPRETATION: This study in individuals with type 2 diabetes and diabetic kidney disease suggests that the beneficial effects of angiotensin receptor blockers are similar in male and female participants for the kidney outcome but not for the cardiovascular outcome. More attention to sex differences in angiotensin receptor blockers' efficacy and underlying mechanisms of differences in response is needed.
ClinialTrials.gov NCT00308347.
目的/假设：我们的目的是评估血管紧张素受体阻滞剂（即氯沙坦和厄贝沙坦）对2型糖尿病和糖尿病肾病患者肾脏及心血管结局疗效的性别差异。
使用了血管紧张素II拮抗剂氯沙坦研究（RENAAL）和厄贝沙坦II型糖尿病肾病试验（IDNT）的数据。肾脏结局为首次出现终末期肾病或血清肌酐翻倍的时间。心血管结局为首次出现中风、心肌梗死、心血管死亡或因心力衰竭住院的复合事件的时间。在Cox比例风险模型中通过性别×治疗交互项评估性别差异。
纳入1737名男性参与者和924名女性参与者。血管紧张素受体阻滞剂对肾脏结局的有益作用在男性和女性参与者中相似（男性参与者的风险比为0.72 [95%置信区间0.59, 0.86]，女性参与者为0.86 [95%置信区间0.69, 1.06]；性别×治疗交互风险比为1.19 [95%置信区间0.89, 1.59]）。对于心血管结局，血管紧张素受体阻滞剂降低了男性参与者的风险，但未降低女性参与者的风险（男性参与者的风险比为0.81 [95%置信区间0.69, 0.95]，女性参与者为1.11 [95%置信区间0.88, 1.40]；性别×治疗交互风险比为1.37 [95%置信区间1.03, 1.82]）。
结论/解读：这项针对2型糖尿病和糖尿病肾病患者的研究表明，血管紧张素受体阻滞剂对肾脏结局的有益作用在男性和女性参与者中相似，但对心血管结局并非如此。需要更多关注血管紧张素受体阻滞剂疗效的性别差异以及反应差异的潜在机制。
ClinicalTrials.gov NCT00308347
