The effects of incretins as a double-edged sword on cancer

Incretins, such as Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic peptide (GIP), are hormones known to stimulate insulin secretion and are widely used in the management of type 2 diabetes mellitus (T2DM). Recent evidence suggests that these hormones, and incretin-based therapies like DPP-4 inhibitors and GLP-1 receptor agonists, may have proliferative effects on pancreatic β-cells, raising concerns about a potential link to certain cancers. This review aims to evaluate both the beneficial and detrimental effects of incretins in cancer development and therapy.

We conducted a comprehensive review of clinical cohort studies, as well as in vivo and in vitro investigations, to assess the dual role of incretin-based therapies in cancer risk and potential treatment. The molecular and cellular mechanisms underlying these effects were critically analyzed.

While some studies have suggested an increased risk of pancreatic, thyroid, cholangiocarcinoma, and colorectal cancers associated with incretin therapies-especially in genetically predisposed individuals-other research has demonstrated anticancer effects in prostate, breast, ovarian, and other cancers through various mechanisms. These include inhibition of tumor proliferation, induction of apoptosis, and modulation of immune responses.

Although incretin-based drugs may pose a cancer risk in specific tissues, particularly in susceptible individuals, their therapeutic potential in mitigating other cancer types appears promising. The overall evidence suggests that the benefits of incretins may outweigh the risks when patient-specific factors are carefully considered.