AbstractObjectiveSevere acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) uses the host’s angiotensin‐converting enzyme 2 (ACE2) as a cellular entry point. Therefore, modulating ACE2 might impact SARS‐CoV‐2 viral replication, shedding, and coronavirus disease 2019 (COVID‐19) severity. Here, it was investigated whether the angiotensin II type 1 receptor blocker valsartan alters the expression of renin‐angiotensin system (RAS) components, including ACE2, in human adipose tissue (AT) and skeletal muscle.MethodsA randomized, double‐blind, placebo‐controlled clinical trial was performed, in which 36 participants (BMI 31.0 ± 0.8 kg/m2) with impaired glucose metabolism received either valsartan or placebo for 26 weeks. Before and after 26 weeks’ treatment, abdominal subcutaneous AT and skeletal muscle biopsies were obtained, and gene expression of RAS components was measured by quantitative reverse transcription polymerase chain reaction.ResultsValsartan treatment did not significantly impact the expression of RAS components, including ACE2, in AT and skeletal muscle.ConclusionsGiven the pivotal role of ACE2 in SARS‐CoV‐2 spread and the clinical outcomes in COVID‐19 patients, the data suggest that the putative beneficial effects of angiotensin II type 1 receptor blockers on the clinical outcomes of patients with COVID‐19 may not be mediated through altered ACE2 expression in abdominal subcutaneous AT.