flow trial semaglutide kidney outcomes nejm 2024 hazard ratio 0.76 FLOW: outcome results for GLP-1RA FLOW clinical Trial (funded by

This increases: hepatic fat oxidation energy expenditure triglyceride mobilization References: Habegger KM et al., Nature Medicine , 2010 Kim T et al., Cell Metabolism , 2018 Clinical Trial Evidence Obesity (Phase 2) Key outcomes: up to 24% body weight reduction majority of weight loss from fat mass Reference: Type 2 Diabetes Observed effects: HbA1c reduction improved glycemic control reduced insulin resistance Reference: Body Composition Effects Retatrutide appears to: reduce visceral adipose tissue reduce hepatic steatosis preserve lean mass when combined with resistance training Reference: Gastaldelli A et al., Diabetes , 2020 Neurological Research Context GLP-1 receptors are expressed in multiple brain regions including: hippocampus hypothalamus cortex These pathways may influence: neuroinflammation neuronal energy metabolism cognitive signaling Reference: Hlscher C, Nature Reviews Neuroscience , 2014 Cardiovascular and Renal Effects Incretin therapies have demonstrated: improved endothelial function reduced systemic inflammation lower cardiovascular risk markers Reference: Marso SP et al., NEJM , 2016 Safety and Tolerability Common adverse events in trials include: nausea vomiting diarrhea constipation These are generally dose-dependent and improve with titration

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