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Recently, the newly developed drug tirzepatide, which targets both the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, was introduced to the market to treat type 2 diabetes and obesity in 2022 and 2023, respectively (Table 1).25,26 GIP (Figure 1G) is another incretin hormone that triggers insulin secretion when a meal is ingested.27 Tirzepatide (Figure 1H) was designed to bind GLP-1/GIP receptors by modifying the native amino acid sequence of GIP.3,28 The combined activation of GLP-1 and GIP receptors more effectively reduces glucose levels and stimulates weight loss compared to the placebo, semaglutide and dulaglutide, or insulin.2931 Table 1

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GLP-1 analogs are water-soluble and large, which means they cannot diffuse easily