SURMOUNT-1: Tirzepatide 15 mg, the generational leap of 2022 SURMOUNT-1 (Jastreboff et al., NEJM 2022, PMID 35658024) randomized 2,539 obese adults without diabetes to tirzepatide 5, 10, or 15 mg/week or placebo over 72 weeks
Chem Soc Rev 24:401412
Diabetes Care 37:29892995 Uehara K, Yamagishi SI, Otsuki S, Chin S, Yagihashi S (2004) Effects of polyol pathway hyperactivity on protein kinase C activity, nociceptive peptide expression, and neuronal structure in dorsal root ganglia in diabetic mice
DSIP works faster, with sleep pressure reported within hours, but even its full effects on sleep architecture normalization develop over multiple doses

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

Furthermore, the mechanical properties of the regenerating tissues, including the femur-medial collateral ligament-tibia complexes, appeared to be improved in the TB-500 group compared to the control