Weight Loss Interventions Linked to Reduced Obesity-Related Cancer Risk: Study Explores GLP-1 RAs and Bariatric Surgery
Obesity has long been established as a significant risk factor for various types of cancer, impacting both the likelihood of developing the disease and subsequent survival rates. Now, a recent study delves into the potential link between weight-loss interventions, specifically weight loss medications and bariatric surgery, and the risk of developing obesity-related cancers (ORCs). The research suggests that GLP-1 receptor agonists (GLP-1 RAs), a class of medications commonly used for obesity and type 2 diabetes, may offer a surprising benefit in reducing ORC risk, potentially beyond their impact on weight loss alone.
Obesity-related cancers encompass a range of malignancies, including multiple myeloma, meningioma, adenocarcinoma of the esophagus, stomach, colorectal region, liver, bile duct, gallbladder, pancreas, uterus, ovary, renal-cell kidney, thyroid, and postmenopausal breast cancer, as identified by the Centers for Disease Control and Prevention (CDC).
The observational study, conducted by researchers at Clalit Health Services in Tel Aviv, Israel, analyzed the medical records of 6,356 participants aged 24 and older who were diagnosed with both obesity and diabetes but had no prior history of ORCs. The study period spanned from 2010 to 2018. During this time, half of the participants were prescribed GLP-1 RAs, administered as injectable medications, and had at least six prescriptions filled within a 12-month period. The remaining half underwent bariatric metabolic surgery (BMS).
After carefully adjusting for other potentially influential factors, the researchers calculated that ORC incidence occurred in 5.62 cases per 1,000 person-years in the bariatric surgery group, compared to 5.89 cases per 1,000 person-years among those taking GLP-1 RAs. Overall, the study indicated a 41% relative risk reduction for ORCs with GLP1-RAs compared to BMS, highlighting that the benefits extend beyond weight-loss alone.
The findings, published in the journal eClinicalMedicine, suggest that GLP-1 RAs may contribute to a decreased risk of ORC through mechanisms beyond simply facilitating weight loss. "The results point at the existence of additional pathways beyond weight loss in which GLP-1RAs contribute to the decreased risk for obesity-related cancer," stated lead study author Yael Wolff Sagy, PhD, head of research at Clalit Health Services.
Niketa Patel, a professor of molecular medicine with the USF Health Morsani College of Medicine in Tampa, Florida, who was not involved in the study, emphasized the link between obesity and chronic inflammation. Patel noted that GLP1-RAs have demonstrated the ability to reduce inflammation, potentially contributing to a decreased risk of developing ORCs.
Dr. Britta Reierson, MD, medical director of knownwell, a provider of metabolic health services, offered additional insights into the potential cancer-mitigating properties of GLP-1 RAs. She highlighted the anti-inflammatory properties of these medications as addressing a significant risk factor for various cancers. Furthermore, she explained that the metabolic regulation and improvement in metabolic health resulting from these medications, including lowering blood glucose levels and decreasing insulin resistance, could also reduce cancer risk. Dr. Reierson also noted emerging evidence suggesting that GLP-1 RAs may have direct anti-tumor effects, potentially through modulation of immune responses and epigenetic changes, which are changes that occur to gene expression and are passed down to future generations.
Dr. Susan Savery, MD, a board-certified obesity medicine and primary care physician with PlushCare, further elaborated on the mechanisms by which GLP-1 medications may help reduce inflammation. She pointed out that research suggests these medications reduce inflammation not only through weight loss but also in other organs of the body, such as the heart. Chronic inflammation can damage cell DNA and has long been recognized as a risk factor for cancer development. Dr. Savery explained that fat cells (adipose tissue) naturally produce inflammatory cells, and GLP-1 medications, similar to bariatric surgery, can help reduce this inflammation by decreasing the amount of adipose tissue through weight loss.
The researchers acknowledged certain limitations to the study. Being an observational study, there may be residual differences between the comparison groups (individuals who underwent surgery versus those who received GLP1-RAs) despite efforts to account for these differences methodologically. However, they emphasized that only this type of real-life observational study can provide the long follow-up period necessary to evaluate the risk of developing cancer, which often has very long latency periods.
Another limitation cited was that the primary drug included in the study was liraglutide (Saxenda, Victoza), with smaller numbers of people taking exenatide (Byetta) and dulaglutide (Trulicity). The researchers emphasized the importance of evaluating the comparative effectiveness of newer GLP1-RA drugs, which are expected to have a larger effect.
Despite the promising results, the researchers cautioned against premature conclusions and emphasized the need for further research. Sagy stated, "Although the direction of the results is promising, we should wait and see if and how clinical guidelines will consider it."
Reierson concurred, emphasizing the need for larger, randomized, controlled trials to confirm the observed effects and better understand the underlying mechanisms. She also emphasized the importance of investigating the impact of GLP-1 RAs on different types of cancer and assessing the long-term safety and potential side effects of using GLP-1 RAs as a cancer therapy.
Savery agreed that it is likely too early to predict FDA approval for cancer therapy but noted that weight reduction plays an important role in cancer prevention, and GLP-1s seem to offer an additional benefit through inflammation reduction.
While GLP-1 RAs offer valuable support for weight loss, maintaining a healthy lifestyle through nutritious eating and regular physical activity remains the foundation for cancer prevention and better overall health.
