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Overall, efinopegdutide emerged as a promising option for the treatment of NAFLD.144 GLP-1RAs and gastrointestinal cancers GLP-1 and its receptor agonists show some potential in the treatment of gastrointestinal cancers, although this remains an emerging area of research.518,519,520,521 Hepatocellular carcinoma (HCC) Initially developed for treating diabetes, GLP-1RAs have shown potential in treating NASH, which is closely related to HCC.513 Studies suggest that the anti-inflammatory and metabolic effects of GLP-1RAs might also influence the progression of liver diseases, including HCC.503,512,518 These effects include modulating cell proliferation, inflammation, and oxidative stress in liver cells, all of which are key factors in the development and progression of HCC.513,522 In a mouse model induced with NASH-related HCC, treatment with liraglutide (a type of GLP-1RA) was shown to prevent the progression of hepatocellular carcinoma.518 This was observed through improved glycemic control, reduced occurrence of liver cancer, and better liver histology compared to the control group.518 Studies indicate that liraglutide may inhibit liver carcinogenesis through its metabolic effects, suggesting that GLP-1RAs could potentially play a role in preventing or managing HCC in the context of NASH.523 Not only hepatocellular carcinoma, but GLP-1 has also shown potential in the treatment of other gastrointestinal tumors.524,525 Pancreatic cancer Researchers first compared the expression of GLP-1R in human pancreatic cancer tissues with adjacent non-tumorous pancreatic tissues, finding generally lower or absent expression of GLP-1R in pancreatic cancer tissues.520 Subsequently, the study observed that treatment with liraglutide, both in vitro (cell culture models) and in vivo (mouse models), inhibited the tumor formation and metastatic capabilities of pancreatic cancer cells by activating GLP-1R.520 The anti-tumor effect of liraglutide is related to its inhibition of the PI3K/Akt signaling pathway, as the activation of Akt is crucial for promoting cell survival and proliferation, and liraglutide can inhibit this process in a dose-dependent manner.520,526 In the context of T2DM, liraglutide, by regulating the PI3K/Akt pathway and activating GLP-1R, effectively inhibits the growth and spread of pancreatic cancer cells.520 Colorectal cancer The potential impact of GLP-1RAs on colorectal cancer (CRC) treatment is achieved through the modulation of Bone Morphogenetic Protein 4 (BMP4).519 In T2DM and CRC, the regulation of BMP4 is abnormal, which is a key focus of the research.519 Specifically, high blood glucose-induced insulin resistance in CRC cells leads to increased BMP4 expression, which activates the BMP4-Smad1/5/8 signaling pathway.519 The activation of this pathway enhances cell proliferation and metastatic capabilities by promoting epithelial-mesenchymal transition (EMT), thereby increasing the invasiveness and metastatic potential of tumors

Oral GLP-1 formulations produce similar onset of appetite suppression, within one to four weeks, but achieve less total weight loss compared to injectable formulations

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GH Release Comparison Approximate GH pulse amplitude at standard doses (from published research): Note: Individual response varies significantly