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Reviews flag this as an unresolved question, especially in patients with current or prior cancer (Sehgal et al., Pharmaceuticals, 2025)

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The durability of metabolic benefits after washout, the consequences of chronic pan-ERR activation in heart and kidney, and the potential for tolerance or compensatory network changes require longer studies

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Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control