Weight loss drugs known as GLP-1 receptor agonists may help reduce the risk of developing several types of cancer in patients with type 2 diabetes, according to a report by medical experts at the National and Kapodistrian University of Athens. The findings are based on a large retrospective analysis tracking 1.65 million patients over a period of up to 15 years.
The observational study compared patients taking GLP-1 receptor agonists against those treated with insulin or metformin. When compared with insulin, patients using GLP-1 medications experienced a significantly lower incidence of 10 out of 13 cancers associated with obesity, including a 59 percent lower risk of pancreatic cancer and a 53 percent lower risk of hepatocellular carcinoma, a form of liver cancer.
The analysis was highlighted by Professor of Therapeutics, Epidemiology, and Preventive Medicine Theodora Psaltopoulou, Dr. Maria Kaparelou, an internist and oncologist, and Professor of Therapeutics, Oncology, and Hematology Thanos Dimopoulos. All three researchers are affiliated with the Therapeutics Clinic at Alexandra Hospital in Athens, where Dimopoulos serves as clinic director and is a former rector of the University of Athens.
Biological link between excess fat and tumor growth
Medical research has established that obesity is one of the most critical modifiable risk factors for cancer development, second only to tobacco smoking. Global estimates indicate that between 4 percent and 8 percent of all cancers worldwide are directly attributable to excess body fat.
Excess adipose tissue accumulation is linked to an elevated risk of 13 specific malignancies:
- Esophageal adenocarcinoma
- Breast cancer
- Colorectal cancer
- Endometrial cancer
- Stomach cancer
- Gallbladder cancer
- Kidney cancer
- Ovarian cancer
- Pancreatic cancer
- Liver cancer
- Multiple myeloma
According to the Greek research team, the connection between obesity and cancer rests on strong biological mechanisms. Obesity is accompanied by hyperinsulinemia and the activation of the insulin-like growth factor-1 (IGF-1) axis. These biological pathways promote rapid cell proliferation while suppressing apoptosis, the process of programmed cell death that normally eliminates damaged cells.
In addition, increased activity of the enzyme aromatase in fat tissue leads to higher estrogen exposure throughout the body. Alterations in adipokines, characterized by elevated levels of leptin and reduced levels of adiponectin, combine with chronic low-grade inflammation to form a cellular microenvironment that encourages cancer formation.
Comparing GLP-1 treatments against insulin and metformin
To evaluate whether GLP-1 receptor agonists offer cancer protection beyond weight reduction and improved metabolic health, researchers examined medical records from 1.65 million patients diagnosed with type 2 diabetes. The long-term study monitored health outcomes for up to 15 years.
The results demonstrated that patients on GLP-1 therapies had lower rates of colorectal, endometrial, kidney, ovarian, and gallbladder cancers, as well as multiple myeloma, compared to those taking insulin. The most substantial reductions were observed in pancreatic cancer, which dropped by 59 percent, and liver cancer, which decreased by 53 percent.
However, the comparison yielded different results when GLP-1 receptor agonists were evaluated against metformin, another standard diabetes medication. When compared to metformin, GLP-1 agonists showed no statistically significant reduction in the incidence of the same 13 malignancies. Furthermore, GLP-1 treatment was associated with an increased relative risk of kidney cancer when compared directly with metformin.
Researchers urge cautious interpretation of findings
The authors of the review stressed that the findings must be interpreted with caution. Chronic hyperinsulinemia is a key driver linking obesity and insulin resistance to cancer development. Consequently, the lower cancer rates seen in GLP-1 users relative to insulin users may reflect the risks of insulin therapy rather than a direct anti-cancer effect from GLP-1 drugs.
Furthermore, because the data comes from retrospective observational studies, it cannot establish a direct cause-and-effect relationship. The observed correlations could be influenced by differences in baseline patient health, variations in the frequency of cancer screening tests, or differing levels of actual medication adherence.
The researchers also noted that much of the historical data predates the widespread clinical adoption of modern GLP-1 and dual-action therapies such as semaglutide and tirzepatide in individuals with obesity who do not have type 2 diabetes. Long-term cancer outcomes for non-diabetic patients using these newer medications remain limited.
Future outlook for metabolic health and cancer prevention
Based on current evidence, experts emphasize that GLP-1 receptor agonists cannot be considered cancer prevention drugs or prescribed solely to reduce oncological risk. However, the study reinforces the fundamental concept that metabolic health and cancer prevention are deeply interconnected.
Effective management of obesity through lifestyle modifications, metabolic intervention, and appropriate medical therapy may serve in the long run as a valuable tool for primary cancer prevention. Future long-term prospective studies will be required to determine whether GLP-1 medications provide independent anti-cancer protection beyond the benefits of weight loss and improved insulin sensitivity.
