Key result
Olmesartan significantly increased serum Ang-(1–7) levels compared to amlodipine over 24 weeks in patients with type 2 diabetes and hypertension.
Why the study?
Recent studies suggest ACE2 and Ang-(1-7) may have beneficial cardiovascular effects, but the impact of olmesartan on their levels and on kidney and vascular function in type 2 diabetes and hypertension needed investigation.
Does olmesartan increase serum Ang-(1-7) levels compared to amlodipine in patients with type 2 diabetes and hypertension?
RCT (n=80)
1:1
No
Does olmesartan increase serum Ang-(1-7) levels compared to amlodipine in patients with type 2 diabetes and hypertension?
p-value: p=0.01
In patients with type 2 diabetes and hypertension, olmesartan significantly increased serum ACE2 and Ang-(1-7) levels compared to amlodipine, and these increases were independently associated with a reduction in albuminuria.
Olmesartan may confer RAS-modulating benefits in T2D hypertension; extends ARB vs CCB evidence to Ang-(1-7) elevation.
BACKGROUND: Recent studies suggest that angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1-7) [Ang-(1-7)] might have beneficial effects on the cardiovascular system. We investigated the effects of olmesartan on the changes in serum ACE2 and Ang-(1-7) levels as well as kidney and vascular function in patients with type 2 diabetes and hypertension. METHODS: This was a prospective, randomized, active comparator-controlled trial. Eighty participants with type 2 diabetes and hypertension were randomized to receive 20 mg of olmesartan (N = 40) or 5 mg of amlodipine (N = 40) once daily. The primary endpoint was changes of serum Ang-(1-7) from baseline to week 24. RESULTS: Both olmesartan and amlodipine treatment for 24 weeks decreased systolic and diastolic blood pressures significantly by > 18 mmHg and > 8 mmHg, respectively. Serum Ang-(1-7) levels were more significantly increased by olmesartan treatment (25.8 ± 34.5 pg/mL → 46.2 ± 59.4 pg/mL) than by amlodipine treatment (29.2 ± 38.9 pg/mL → 31.7 ± 26.0 pg/mL), resulting in significant between-group differences (P = 0.01). Serum ACE2 levels showed a similar pattern (6.31 ± 0.42 ng/mL → 6.74 ± 0.39 ng/mL by olmesartan treatment vs. 6.43 ± 0.23 ng/mL → 6.61 ± 0.42 ng/mL by amlodipine treatment; P < 0.05). The reduction in albuminuria was significantly associated with the increases in ACE2 and Ang-(1-7) levels (r = - 0.252 and r = - 0.299, respectively). The change in Ang-(1-7) levels was positively associated with improved microvascular function (r = 0.241, P < 0.05). Multivariate regression analyses showed that increases in serum Ang-(1-7) levels were an independent predictor of a reduction in albuminuria. CONCLUSIONS: These findings suggest that the beneficial effects of olmesartan on albuminuria may be mediated by increased ACE2 and Ang-(1-7) levels. These novel biomarkers may be therapeutic targets for the prevention and treatment of diabetic kidney disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT05189015.
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Kim et al. (2023) conducted an RCT in Type 2 diabetes and hypertension (n=80). Olmesartan vs. Amlodipine 5 mg once daily (titrated to 10 mg if needed) was evaluated on Change in serum Ang-(1–7) levels from baseline to week 24 (p=0.01). Olmesartan significantly increased serum Ang-(1–7) levels compared to amlodipine over 24 weeks in patients with type 2 diabetes and hypertension.
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