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In 2023, Real Housewives of New Jersey star Margaret Josephs told me that her doctor at a "metabolic aesthetics" clinic was giving her a "cocktail" of a GLP-1 and various peptides — what's now commonly referred to as a "stack." Meanwhile, people became more aware of alternative sources for the drugs: Compounding pharmacies and the " gray market ," where research versions of semaglutide and tirzepatide, as well as peptides with no FDA-approved analogs, are sold

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Additionally, Protein kinase C (PKC) pathway activation can induce insulin receptor substrate 1 (IRS-1) phosphorylation, inhibiting insulin signaling through downstream effectors such as Akt, phosphoinositide 3-kinase (PI3K), and glucose transporter 4 (GLUT-4) (Ritter et al., 2015