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At tissue level, RAS (renin-angiotensin system) can be upregulated with non-hemodynamic effects ( Several studies reported that inappropriate ANGII/AT1R activation occurs because of different mechanisms, particularly in patients with T2DM

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At higher doses: Some participants experienced dysesthesia , an abnormal skin sensation Discontinuation rates were higher than placebo A portion of discontinuations were attributed to excessive weight loss , underscoring the importance of careful dosing and clinical oversight Additional late-stage trials are ongoing and will further clarify safety, tolerability, and optimal dosing strategies