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Data Animal Data In pregnant rats given twice weekly subcutaneous doses of 0.02, 0.1, and 0.5 mg/kg tirzepatide (0.03-, 0.07-, and 0.5-fold the MRHD of 15 mg once weekly based on AUC) during organogenesis, increased incidences of external, visceral, and skeletal malformations, increased incidences of visceral and skeletal developmental variations, and decreased fetal weights coincided with pharmacologically-mediated reductions in maternal body weights and food consumption at 0.5 mg/kg
The active ingredient is the same, so transitioning is relatively straightforward
Manifestations of hepatic oxidative damage include dysregulation of lipid metabolism (leading to steatosis), hepatocyte degeneration and death, and activated immune response (leading to inflammation and fibrosis/cirrhosis)
The reduction of roGFP2(S 2 ) is therefore a good example for an enzyme using an alternative reaction pathway to overcome a kinetic challenge, and we hypothesize that other non-glutathione disulfide substrates with reactive proximal cysteinyl residues and rather negative redox potentials also require a ternary complex for their reduction
Together, these data reveal a sex-dependent requirement for NRF2 in the absence of GSH over time
