Experts at Moffitt Cancer Center are Optimistic that GLP-1 Agonists Might Transform Cancer Care in Obesity
According to the Centers for Disease Control and Prevention (CDC), being overweight or obese puts an individual at an increased risk of developing a myriad of serious diseases and health conditions, including 13 different types of cancer. Between 2005 and 2014, most instances of cancer associated with obesity increased in the United States, while cancers related to other factors decreased, with body composition and excessive fat distribution contributing to considerably worse prognoses. Currently, obesity-related cancers make up roughly 40% of all new diagnoses in the United States annually.
Uterine cancer is one such pathology that is becoming more prevalent, and it is recognized that obesity is the greatest known risk factor for its occurrence. As women age and transition through menopause, excess body fat can lead to higher concentrations of serum estrogen which directly impacts the health of the inner lining of the uterus, or endometrium. Without monthly sloughing and hormonal control, rapid proliferation and division of the endometrial cells can result in cellular mutations that increase the risk of cancer. Traditional treatment methods rely on proper staging and grading, but even confined instances of endometrial cancer (EC) can result in high recurrence rates after achieving remission.
Over the past several years, a new class of prescription drugs, glucagon-like peptide-1 (GLP-1) receptor agonists, have become very popular for their ability to cause pronounced weight loss through appetite control, reduced caloric intake, and slower digestion. Originally intended for use as first-line therapy to treat type 2 diabetes (T2D), these medications later became FDA-approved to treat obesity.
As the science and understanding of the secondary effects of GLP-1 agonists continue to expand, experts have posited whether they might also be used to prevent, or even treat, obesity-related cancers. Dr. Monica Avila, a gynecologic oncologist in the Gynecologic Oncology Program at Moffitt Cancer Center, imagines a world where this just might be the case!
In July 2024, a study was published that sought to uncover clinical evidence to support the use of GLP-1 agonists to prevent obesity-associated cancers (OACs). Using a nationwide, multicenter database of electronic health records (EHRs), researchers compared the incident risk of each of the 13 OACs in over 1.65 million cancer-naïve patients with T2D prescribed GLP-1 agonists, insulin therapy, or oral metformin from March 2005 to November 2018.
Compared with the overall effects of insulin, GLP-1 agonists exhibited a significant risk reduction in ten of the 13 OACs, including gallbladder cancer, pancreatic cancer, meningioma, hepatocellular carcinoma, colorectal cancer, esophageal cancer, endometrial (uterine) cancer, ovarian cancer, multiple myeloma, and kidney cancer. The risk of post-menopausal breast cancer neither increased nor decreased in women with T2D-prescribed GLP-1 agonists compared to those being treated with insulin or metformin. Until now, thyroid cancer risk in this population has been deemed inconclusive, yet there is mounting evidence from multiple studies to suggest that GLP-1 agonists may be associated with increased risk. Relative to metformin use, GLP-1 agonists revealed an increased risk of kidney cancer, but a decrease. risk compared to insulin use. Specific to uterine cancer, there seems to be increased expression of the GLP1 protein receptor which suggests using a GLP1 medication against this could be effective6. In uterine cancer cells, they have shown that the use of GLP1 agonists decreases cell growth and was hopeful this could work similarly in humans.
With this growing body of knowledge, clinical experts have been incorporating prescriptions for GLP-1 agonists into comprehensive weight loss treatment plans to stop the problem at its source. Along with customized diet and lifestyle changes, behavioral therapy, and when indicated, bariatric surgery, patients can achieve effective, sustainable results to treat obesity.
It remains unclear whether the reduction in cancer risk in obese patients is due to considerable weight loss or whether there is something inherently protective in this class of drugs themselves. More clinical research is necessary to change clinical practice and fully comprehend whether GLP-1 agonists might offer primary prevention of cancer.
Furthermore, clinical trials are just starting to be underway to assess the effects of GLP-1 agonists to treat uterine cancer that could ultimately save women’s lives and preserve their fertility. It will take several years to know the results, but many patients are already on these medications for FDA-approved indications such as diabetes. Dr. Avila is hopeful that the addition of GLP-1 agonists will not only prevent recurrence but also have the potential to counteract the very mechanisms that cause uterine cancer.
The Gynecologic Oncology Program at Moffitt Cancer Center offers comprehensive and innovative treatment options for patients with gynecologic cancers. Our multidisciplinary team can collaborate with referring providers on the diagnoses and develop a personalized treatment plan for our shared patients.
To refer a patient with gynecologic cancer or with suspicious tumor findings, please complete our online form or contact a physician liaison for assistance. As part of our efforts to shorten referral times as much as possible, online referrals are typically responded to within 24 - 48 hours.
