In a recent study published in the journal JAMA Network Opena team of researchers evaluated the relationship between glucagon-like peptide 1 receptor agonists (GLP-1RAs) (drugs that mimic the hormone GLP-1 to lower blood sugar) and the risk of thirteen obesity-related cancers (OACs ) in patients with type 2 diabetes (T2D), compared to those prescribed insulin or metformin.
Study: Glucagon-like peptide-1 receptor agonists and 13 obesity-related cancers in patients with type 2 diabetes. Image credit: fotogurmespb / Shutterstock
Record
OACs are thirteen malignancies associated with excess body fat, increase cancer risk and worsen prognosis, and are further exacerbated by T2D. GLP-1RAs are effective in treating T2D, promoting weight loss, reducing adverse cardiovascular outcomes, and resolving nonalcoholic steatohepatitis. They are hypothesized to reduce the risk of OACs, as evidenced by their association with a lower risk of colon cancer. However, systematic clinical evidence is limited, which warrants further research to evaluate the potential benefits of GLP-1RAs in reducing the risk of all thirteen OACs.
About the study
The study used the TriNetX platform to access proven electronic health records (EHRs) of 113 million patients from 64 healthcare organizations in the United States (US), representing diverse demographic groups. The platform supports patient-level analyzes and has been used in several retrospective cohort studies.
EHR data included demographics, diagnoses, medications, procedures, laboratory tests, genomics, visits, and socioeconomic information, with oncology data from cancer registries. Self-reported gender, race, and ethnicity data were standardized, with missing values flagged as “unknown.”
The study included 1,651,452 patients with T2D without a history of 13 OACs who were prescribed GLP-1RA, insulin, or metformin between March 2005 and November 2018. Patients were categorized into exposure (GLP-1RA/no insulin or GLP-1RA/no ) and comparison groups (insulin/no GLP-1RA or metformin/no GLP-1RA). Each OAC was examined separately in groups with propensity score matching for relevant covariates. Follow-up continued until the occurrence of the outcome, death, loss to follow-up, or 15 years.
The 13 OACs included cancers of the esophagus, breast, colon, stomach, kidney, ovary, endometrium, gallbladder, pancreas, thyroid, hepatocellular carcinoma (a type of liver cancer that originates in liver cells), meningioma (a tumor that forms in the membranes covering the brain and spinal cord) and multiple myeloma (cancer of the plasma cells in the bone marrow). Cox proportional hazard and Kaplan–Meier survival analyzes compared event rates, calculating hazard ratios (HRs) and 95% confidence intervals (CIs). Statistical analyzes were performed using the platform’s built-in functions in R, Python, and Java. Data collection and analysis was completed on April 26, 2024.
Study results
The study analyzed 1,651,452 patients with T2D, with a mean age of 59.8 years, including 827,873 men and 775,687 women. The racial makeup included 0.4% American Indian or Alaska Native, 4.0% Asian, 17.0% Black, 0.8% Native Hawaiian or Other Pacific Islander, and 60.6% White participants. To compare GLP-1RAs with insulins, 1,093,728 patients without a previous diagnosis of OAC were included. The GLP-1RA/no insulin group consisted of 48,983 patients, while the insulin/no GLP-1RA group had 1,044,745 patients. The GLP-1RA group was younger, had a higher proportion of female and white participants, and had higher rates of family history of cancer, obesity, cancer screening, and prior use of other antidiabetic agents.
The analysis showed that GLP-1RAs were associated with a significantly lower risk of 10 of 13 OACs compared with insulins. These included gallbladder cancer (HR, 0.35), meningioma (HR, 0.37), pancreatic cancer (HR, 0.41), hepatocellular carcinoma (HR, 0.47), ovarian cancer (HR, 0.52), colon cancer (HR, 0.54), multiple myeloma (HR, 0.59), esophageal cancer (HR, 0.60), endometrial cancer (HR, 0.74), and kidney cancer ( HR, 0.76). Although the HR for gastric cancer was less than 1, it was not statistically significant (HR, 0.73). GLP-1RAs did not significantly affect the risk of postmenopausal breast cancer or thyroid cancer. The cumulative incidences of colon and liver cancer were lower in the GLP-1RA group compared with the insulin group. The median follow-up time for colon cancer was approximately 2075 days for the GLP-1RA group and 1982 days for the insulin group, while for liver cancer, it was approximately 2023 days for the GLP-1RA group and 2038 days for the insulin group.
When comparing GLP-1RAs with metformin, the study included 888,525 patients without a previous OAC diagnosis. The GLP-1RA/no metformin group had 32,365 patients and the metformin/no GLP-1RA group had 856,160 patients. Propensity score matching was used for each OAC outcome. GLP-1RAs were not associated with a lower risk of colon cancer, gallbladder cancer, and meningioma compared with metformin, but were associated with an increased risk of kidney cancer. The cumulative incidences of colon and liver cancer showed no significant difference between GLP-1RAs and metformin. The median follow-up time for colon cancer was approximately 1967 days for the GLP-1RA group and 2102 days for the metformin group, while for liver cancer, it was approximately 1971 days for the GLP-1RA group and 2130 days for metformin group.
conclusions
In summary, analyzing over 15 years of EHRs from a US cohort of more than 100 million people, researchers found that GLP-1RAs significantly reduced the risk of 10 of 13 OACs in patients with T2D compared with insulins. These included cancers of the esophagus, colon, kidney, pancreas, gallbladder, ovary, endometrium and liver, as well as meningioma and multiple myeloma. Compared with metformin, GLP-1RAs showed non-significant risk reductions for some OACs but an increased risk for kidney cancer.
