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The case for plausible benefit: Many mechanisms (weight loss, blood pressure, inflammation) are not diabetes-specific Obesity-related kidney disease is common in non-diabetic CKD Cardiovascular benefits (SELECT trial) are independent of diabetes The case for uncertainty: FLOW did not enroll non-diabetic patients Hyperglycemia is a major driver in DKD that is absent in many non-diabetic CKD cases The optimal dose for non-diabetic CKD may differ from the 1.0 mg used in FLOW Dedicated trials in non-diabetic CKD are in design

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This disruption is thought to affect the normal processes of synaptic plasticity, cognitive development, and motor coordination, contributing to the characteristic symptoms of the syndrome