TY - JOUR
T1 - Sex differences in the efficacy of angiotensin receptor blockers on kidney and cardiovascular outcomes among individuals with type 2 diabetes and diabetic kidney disease
T2 - post hoc analyses of the RENAAL and IDNT trials
AU - de Vries, Sieta T.
AU - Pena, Michelle J.
AU - Tye, Sok Cin
AU - Peters, Sanne A.E.
AU - van Raalte, Daniël H.
AU - Arnott, Clare
AU - Voors, Adriaan A.
AU - Mol, Peter G.M.
AU - Denig, Petra
AU - Heerspink, Hiddo J.L.
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
PY - 2025/3
Y1 - 2025/3
N2 - 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. Methods: 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. Results: 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. Trial registration: ClinialTrials.gov
AB - 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. Methods: 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. Results: 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. Trial registration: ClinialTrials.gov
KW - Angiotensin receptor blockers
KW - Cardiovascular outcome
KW - Diabetic kidney disease
KW - Kidney outcome
KW - Renin–angiotensin system
KW - Sex differences
UR - http://www.scopus.com/inward/record.url?scp=85212117046&partnerID=8YFLogxK
U2 - 10.1007/s00125-024-06325-y
DO - 10.1007/s00125-024-06325-y
M3 - Article
AN - SCOPUS:85212117046
SN - 0012-186X
VL - 68
SP - 507
EP - 515
JO - Diabetologia
JF - Diabetologia
IS - 3
M1 - doi.org/10.1007/s00125-024-06325-y
ER -