Potential role of glucagon like peptide (GLP)-1 receptor agonist to reduce risk of colorectal cancer?

Abstract

Type 2 diabetes and obesity are both independently associated with an increased risk of colorectal cancer. A study conducted by researchers at Case Western Reserve University published in the journal JAMA Oncology has now reported that GLP-1 may reduce the risk of colorectal cancer.¹

Using a national database to identify more than 100 million patients electronic health records, the researchers conducted a population-based study of 1 221 218 patients with type 2 diabetes. Patients were prescribed with anti-diabetic agents from 2005 to 2019 and had no prior antidiabetic agents (drug naïve) use and no previous history of colorectal cancer. The cohorts were propensity-matched, to adjust for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors (exercise, diet, smoking, and alcohol drinking), and procedures such as colonoscopy. Investigators then examined the effects of GLP-1 receptor agonist on their incidence of colorectal cancer compared to those prescribed with other anti-diabetic drugs. The outcome was the first diagnosis of colorectal cancer within 15 years of the first prescription of anti-diabetic therapies.

During a 15-year follow-up, among 22 572 patients treated with insulin, there were 167 case of colorectal cancer compared with 94 cases among matched number of patients receiving GLP-1 receptor agonist—a 44% reduction in the risk of developing colorectal cancer with a GLP-1 receptor agonist. Similarly, in a comparison of 18 518 patients with type 2 diabetes treated with metformin, compared to match number of patients with type 2 diabetes treated with GLP-1 receptor agonist, the latter was associated with a 25% reduction in the risk of developing colorectal cancer. Consistent findings were observed in women and in men. GLP-1RAs were also associated with a 50% lower risk for colorectal cancer in patients with obesity/overweight compared with insulin and 42% reduction compared with metformin.

While simple conclusion cannot be made from an observational study such as this, limited by the usual issues of un-adjusted confounders, evidence from this study could form a basis for the need for clinical trials to determine whether GLP-receptor agonist could prevent colorectal cancer. In addition, further study is required to investigate the mechanism for the potential benefit of GLP-1 receptor agonists to prevent colorectal cancer.