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In preclinical models, glucagon agonism has been associated with increased energy expenditure and hepatic lipid mobilization

Tirzepatide (Mounjaro, Zepbound) activates two: GLP-1 and GIP

20 Possible mechanisms are: natriuresis, due to increased atrial natriuretic peptide secretion, GLP-1R activation in the proximal nephron tubule and Na + /H + transporter inhibition (which reduces sodium reabsorption), as well as vasodilation due to nitric oxide-dependent vasodilation (endothelial GLP-1R activation) and direct effects on smooth muscle cells GLP-1R

However, metformin offers minimal appetite suppression, which limits its usefulness as a standalone weight loss tool for patients without diabetes