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This effect is primarily mediated by an increase in the phosphorylation of insulin receptor substrate 1 (IRS1) and a concomitant inhibition of Akt phosphorylation, a crucial component of the insulin signaling pathway

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Studies through 2025 show that after stopping semaglutide, approximately 50-70% of lost weight returns within the first year without concurrent lifestyle modifications

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Managing this side effect is important because if people cannot stick with their semaglutide treatment, they may not get the full benefit of weight loss