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While GIP has lost most of its insulinotropic activity in patients with T2D, GLP-1 has retained enough of its insulinotropic activity to stimulate insulin secretory responses even in patients with T2D [55]

The multifaceted mechanism of action of 5FU involves direct incorporation of its metabolites into DNA (FdUTP) and RNA (FUTP), as well as inhibition of thymidylate synthase (TS) via FdUMP 4,5 , making it more difficult to identify rational combination partners that would enhance clinical responses without eliciting adverse systemic toxicity