Researchers at Case Western Reserve University say that a class of diabetes drugs used to treat type 2 diabetes may reduce the risk of the development of colorectal cancer (CRC). The drugs, called glucagon-like peptide-1 receptor agonists, or GLP-1 RAs are medications that are given by injection to lower blood sugars, improve insulin sensitivity, and can help manage weight. This class of drugs has also recently taken off as a weight loss medication.
Results of the study were published this week in the journal JAMA Oncology.
“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular anti-diabetic drugs, such as Metformin or insulin, at preventing the development of CRC,” said co-lead researcher Nathan Berger, a professor at the Case Western Reserve School of Medicine.
Added Rong Xu, co-lead researcher and professor at the School of Medicine: “To our knowledge, this is the first indication this popular weight-loss and anti-diabetic class of drug reduces incidence of CRC, relative to out anti-diabetic agents.”
GLP-1 RAs, which have also been shown to reduce rates of cardiovascular diseases, were shown in this study to produce protective effects against CRC—which is considered an obesity-related cancer—regardless of whether a patient was overweight or obese.
GLP-1 receptor is a G protein-coupled receptor (GPCR) which, when it binds to the GLP-1 ligand, activates signaling pathways that regulate insulin secretion, glucose metabolism, and curbs hunger. GLP-1 is released by L cells in the intestine in response to the presence of nutrients.
Because of the role of the intestine on releasing GLP-1, the Case Western investigators hypothesized that in addition to GLP-1 RAs being effective against diabetes and as a weight-loss drug, that it might also be protective against development of CRC.
For their retrospective study, the investigators tapped a national database that contains more than 100 million electronic health records (EHRs). The team conducted their study on the data of more than 1.2 million patients who had been treated with diabetes drugs between 2005 and 2019. The Case Western team then compared the incidence rates of the development of colorectal cancer in patients treated with GLP-1 RAs to those who had been treated by other means.
Of the more than 22,527 patients who were treated with insulin, there were 167 reported cases of CRC, while a matched set of 22,527 patients treated with GLP-1 RAs revealed only 94 cases of CRC—an incidence rate 44 percent lower. Similarly, matched sets of 18,518 patients treated with either Metformin versus GLP-1 RAs showed a 25 percent reduction of CRC development among the GLP-1 RA group.
Study limitations included potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases inherent in observational studies. As such, the research team noted further studies are warranted to investigate the effects in patients with prior anti-diabetic treatments, underlying mechanisms, potential differential effects within GLP-1RAs, and effects of GLP-1RAs on other obesity-associated cancers.