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No, semaglutide-related fatigue is a normal metabolic adaptation and not dangerous

Availability of data and materials Not applicable Abbreviations CMD: CMD HDL: high-density lipoprotein LDL: low-density lipoprotein OxLDL: Oxidized LDL TG: triglycerides VLDL: very-low-density lipoprotein ATP III: Adult Treatment Panel III IDF: International Diabetes Foundation (NCEP): National Cholesterol Education Program TNF-: tumour necrosis factor-alpha IL: interleukin MCP-1: macrophage chemo-attractant protein 1 ROS: reactive oxygen species RNS: reactive nitrogen species XO: xanthine oxidase eNOS: uncoupled endothelial nitric oxide synthase HO: heme oxygenase XDH: xanthine dehydrogenase Ang II: angiotensin II GDP: guanosine diphosphate PI (3) P: phosphatidylinositol 3-phosphate BH 4 : tetrahydrobiopterin ECs: endothelial cells SMCs: smooth muscle cells GTP: guanosine-5-triphosphate MAPKs: mitogen-activated protein kinases ERK: extracellular signal-regulated kinases NO: nitric oxide NOX: nicotinamide adenine dinucleotide phosphate oxidase O 2 - : superoxide anion radicals ONOO - : peroxynitrite ECM: extracellular matrix HIF: hypoxia-inducible factor SOD: superoxide dismutase H 2 O 2 : hydrogen peroxide GPx: glutathione peroxidase PON: paraoxonases CO: carbon monoxide Trx: thioredoxin SR: sarcoplasmic reticulum SERCA: sarcoplasmic reticulum ATPase HNE: 4-hydroxyl 2-nonenal COX: cyclooxygenase RAAS: renin-angiotensin-aldosterone system IRS: insulin receptor substrate PI3K: phosphatidylinositol 3-kinase RBP: retinol-binding protein GLUT: glucose uptake transporter AT 1 R: angiotensin II type 1 receptor VSMCs: vascular smooth muscle cells NF-kB: nuclear factor-kappa B LOX: lipooxygenase VCAM: ICAM PDGF: platelet-derived growth factor SMC: smooth muscle cells MMP: matrix metalloproteinases IGF-1: insulin-like growth factor-1 FAO: Fatty acid oxidation PCI: percutaneous coronary intervention DES: drug eluting stent References Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, et al

Once retatrutide is tolerated at the 2 mg/week step typically 812 weeks in community references describe introducing cagrilintide at 0.25 mg/week and following a separate 4-week titration to maintenance

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