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Here is a great new review paper on the topic if you want to dig into this more: Leptin resistance: underlying mechanisms and diagnosis

[4] That selectivity profile is relevant to the liver because cortisol itself is a potent driver of hepatic gluconeogenesis and visceral fat accumulation

Mechanistically, we demonstrated that intracellular BPC157 interacts with the E3 ubiquitin ligase adaptor FBXO22 via its proline residue at position 3

The Lancet, DOI: 10.1016/S0140-6736(25)01073-6 [5] Rohit Loomba, M.D., M.H.Sc

That changed in 2025 and 2026 with the FDA approval of two oral options: the Wegovy pill (oral semaglutide, approved December 2025) and Foundayo (orforglipron, approved April 2026)