Researchers found that a class of medications used for type 2 diabetes, called GLP-1 RAs, significantly lowered the risk of this malignancy compared to other diabetes drugs like insulin or metformin.
Glucagon-like peptide-1 (GLP-1), a 30-amino acid peptide secreted by L cells in the distal ileum, colon, and pancreatic α cells, exerts profound glycemic regulatory effects. It binds to the glucagon-like peptide-1 receptor (GLP-1R) on pancreatic β-cells, directly stimulating insulin secretion, promoting β-cell proliferation and differentiation, and inhibiting apoptosis, thereby contributing to a reduction in blood sugar levels. GLP-1 RAs work by activating GLP-1 receptors, leading to similar effects as the natural GLP-1 hormone.
The study, published in JAMA Oncology, suggests GLP-1 RAs could prove valuable not only for managing diabetes and aiding weight loss, but also for warding off colon cancer. This benefit was observed in both overweight and lean patients with diabetes, highlighting the drug's broader potential.
These findings, led by researchers at Case Western Reserve University, have important implications for cancer prevention. With colon cancer ranking as the third most common cancer and the second leading cause of cancer deaths in the US, this potential new line of defense brings significant hope for reducing its burden. The next step is to conduct clinical trials to confirm these findings and explore the mechanisms behind GLP-1 RAs' protective effect against colon cancer.
GLP-1 RAs are effective anti-diabetic and weight-loss agents, which may be related to the incidence of colorectal cancer. In a study, among 22,572 patients with diabetes treated with insulin, there were 167 cases of colorectal cancer, while treated with GLP-1 RAs, there were 94 cases of colorectal cancer. In a similar comparison of 18,518 patients with diabetes treated with metformin compared to 18,518 patients with diabetes treated with GLP-1 RAs, had a 25 percent reduction in colorectal cancer.
Currently, this exciting prospects for preventing colon cancer is found in patients with diabetes, it is unknown if these prospects can be applied to healthy subjects or subjects suffered from other conditions.
While the exact mechanisms through which GLP-1 RAs reduce colorectal cancer risk in diabetic patients are still being investigated, several potential explanations are being explored:
1. Anti-inflammatory effects: GLP-1 RAs possess anti-inflammatory properties, which could help suppress chronic inflammation in the colon, a known risk factor for cancer development. Notably, such anti-inflammatory effects target different pathways in different tissues, underling the broad spectrum of GLP-1RAs actions.
2. Modulation of cell growth and differentiation: They may influence the growth and differentiation of intestinal cells, potentially hindering the growth of precancerous or cancerous cells.
3. Improved insulin sensitivity: GLP-1 RAs enhance insulin sensitivity, leading to better blood sugar control. High blood sugar levels are associated with increased cancer risk, so this improvement could play a role.
4. Weight management: Obesity is a risk factor for colorectal cancer, and GLP-1 RAs can promote weight loss by regulating appetite and satiety. This weight reduction could contribute to the observed cancer risk reduction.
5. Reduced gut microbiome inflammation: Some studies suggest GLP-1 RAs may alter the gut microbiome, reducing inflammation and potentially suppressing carcinogenesis.
It's important to remember that further research is needed to definitively understand the precise mechanisms involved. However, the existing evidence suggests that GLP-1 RAs may offer a promising avenue for protecting diabetic patients from colorectal cancer through multiple pathways.
Reference:
(1) Diabetes drugs may reduce colon cancer risk: study, Taller, 12/07/2023.
(2) Giulia Bendotti et al, The anti-inflammatory and immunological properties of GLP-1 Receptor Agonists, Pharmacol Res. 2022 Aug:182:106320.
(3) Xie Xiao-Yun et al, Glucagon-like peptide-1 improves proliferation and differentiation of endothelial progenitor cells via upregulating VEGF generation, Med Sci Monit. 2011 Feb;17(2):BR35-41.
(4) Daniel J Drucker Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosisMol Endocrinol. 2003 Feb;17(2):161-71.
(5) T D Müller et al, Glucagon-like peptide 1 (GLP-1) Mol Metab. 2019 Dec:30: 72-130.
(6) Jun Chen et al, GLP-1 receptor agonist as a modulator of innate immunity, Front Immunol. 2022 Dec 8:13:997578.
(7) Jennifer A Ligibel et al, Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline, J Clin Oncol. 2022 Aug 1;40(22):2491-2507.
(8) Lindsey Wang et al, GLP-1 Receptor Agonists and Colorectal Cancer Risk in Drug-Naive Patients With Type 2 Diabetes, With and Without Overweight/Obesity, JAMA Oncol. 2023 Dec 7: e235573
