Continuous use was defined as having overlapping successive prescriptions, with a 60 day grace period to bridge consecutive non-overlapping prescriptions
In mouse models where semaglutide lost its acute anti-inflammatory effects when neuronal GLP-1 receptors were knocked out, tirzepatide still effectively prevented TNF-alpha induction
In mouse models of highfat dietinduced liver steatosis, it significantly inhibits hepatic NNMT activity, reduces NAM methylation, increases NAD+ and SAM levels, enhances mitochondrial fatty acid oxidation, reduces hepatic triglyceride and lipid accumulation, lowers lipotoxicity markers (e.g., malondialdehyde, transaminases), improves hepatocellular injury, and reverses steatosis
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Unlike sulfonylureas or insulin, GLP-1 receptor agonists carry a low intrinsic risk of hypoglycemia when used as monotherapy