Glucagon-like peptide 1 receptor agonists (GLP-1RA) may reduce the risk of specific obesity-associated cancers, according to a study by researchers from Case Western Reserve University School of Medicine, Cleveland, OH, that compared the incident risk of each of the 13 OACs in patients with T2D who were prescribed GLP-1RAs vs insulins or metformin.
The authors noted that 13 human malignant neoplasms have been identified as OACs - the presence of excess body fat is associated with increased risk of developing cancer and worse prognosis in patients with these specific tumours. GLP-1RAs are a class of pharmaceuticals are effective agents for the treatment of type 2 diabetes (T2D) and for achieving weight loss, but the association of GLP-1RAs with the incident risk of 13 OACs is unclear.
This retrospective cohort study, based on a nationwide multicentre database of electronic health records (EHRs) of 113 million US patients, included 1,651,452 patients (mean age, 59.8 [15.1] years; 827 873 [50.1%] male and 775 687 [47.0%] female participants) with T2D who had no prior diagnosis of OACs and were prescribed GLP-1RAs, insulins, or metformin during March 2005 to November 2018.
The main outcome was first-time diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure was examined using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied. Hazard ratios (HRs), cumulative incidences and 95% CIs were calculated. All models were adjusted for confounders at baseline by propensity-score matching baseline covariates.
Outcomes
GLP-1RAs compared with insulin were associated with a significant risk reduction in ten of 13 OACs, including in gallbladder cancer, meningioma, pancreatic cancer, hepatocellular carcinoma, ovarian cancer, colorectal cancer, multiple myeloma, oesophageal cancer, endometrial cancer and kidney cancer). Although not statistically significant, the HR for stomach cancer was less than 1 among patients who took GLP-1RAs vs. those who took insulin.
However, GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer. Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant. Compared with metformin, GLP-1RAs were not associated with a decreased risk of any cancers, but were associated with an increased risk of kidney cancer.
The study authors said that the potential cancer-preventative effects of OACs by GLP-1RAs warrant further long-term studies as well as studies of individual newer and possibly more effective antidiabetic and weight loss agents as well as those with multihormone agonist activities.
“It will be important to correlate these associations with the control of T2D and obesity,” the authors concluded. “Moreover, given that T2D and overweight or obesity have negative impacts on patients during cancer therapy, GLP-1RAs should be evaluated for control of these comorbid conditions during cancer therapy as well as for secondary prevention to delay cancer recurrence.”
The findings were featured in the study, ‘Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes’, published in JAMA Network Open. To access this paper, please click here
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