GLP1 Drugs May Benefit Cancer Patients

Over the past few years, the demand for new weight loss medications has skyrocketed, particularly for anti-obesity drugs like semaglutide (Wegovy) and tirzepatide (Zepbound). Known as glucagon-like peptide 1 (GLP-1) agonists, these medications have revolutionized weight loss, becoming vital tools for individuals struggling with obesity. Originally developed for treating type 2 diabetes under different brand names, these drugs have shown promise in addressing conditions beyond weight loss, including reducing inflammation and alleviating symptoms of depression.

Now, researchers and oncologists are exploring the possibility of using these weight loss drugs in cancer care. Although data is still emerging, a few oncologists have begun cautiously integrating GLP-1 agonists into cancer treatment regimens, studying their effects on patients who also struggle with obesity.

The Connection Between Obesity and Cancer Outcomes

Obesity has been shown to reduce the effectiveness of certain cancer therapies and increase the likelihood of treatment-related side effects, particularly in breast cancer patients. Managing a patient’s weight could therefore play a crucial role in improving cancer outcomes, says Dr. Lajos Pusztai, a breast cancer specialist and professor of medicine at Yale School of Medicine.

While Pusztai’s team at Yale has not yet adopted the use of GLP-1 agonists for cancer care, other oncologists are taking steps toward integrating these drugs into their practice. Dr. Neil Iyengar, an oncologist at Memorial Sloan Kettering Cancer Center in New York City, is one of the pioneers in this field. He estimates that around 40% of his breast cancer patients are now on anti-obesity medications to help them manage their weight.

“For patients who have tried everything to reduce their weight but still remain in the obese range, these medications could be a game changer,” said Dr. Iyengar.

How GLP-1 Agonists Work?

GLP-1 is a hormone released by the small intestine after eating, which helps regulate blood sugar by prompting the release of insulin and reducing the production of glucagon. GLP-1 agonists, such as Wegovy (also known as Ozempic when prescribed for diabetes), mimic this hormone, slowing gastric emptying and prolonging the sensation of fullness. Tirzepatide, sold under the brand name Zepbound for weight loss and Mounjaro for diabetes, also stimulates glucose-dependent insulinotropic polypeptide (GIP), which further enhances its ability to promote weight loss.

In a cancer care setting, however, these drugs can exacerbate the nausea and vomiting often caused by chemotherapy, so Dr. Iyengar generally waits until after chemotherapy is complete to prescribe them, using them during maintenance therapy.

Current Use in Cancer Patients

Oncologists typically do not prescribe GLP-1 agonists themselves but instead refer patients to endocrinologists or weight management specialists who manage the prescriptions. Patients then administer the drugs through weekly subcutaneous injections. Dr. Emily Gallagher, an endocrinologist at Mount Sinai Hospital, has prescribed these drugs to hundreds of cancer patients, particularly those receiving hormone therapy for breast cancer. She has also used GLP-1 agonists to help manage weight gain in patients with prostate, endometrial, and multiple myeloma cancers, especially those who have experienced steroid-induced weight gain.

Despite the growing interest, research supporting the use of GLP-1 agonists in cancer care is still limited. Much of the evidence comes from small retrospective studies, especially on breast cancer patients who are taking hormone therapy such as aromatase inhibitors. These studies suggest that while the drugs are safe, they appear to produce significantly less weight loss in cancer patients than in the general population.

A Closer Look at the Data

A study led by Dr. Iyengar, presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting, followed 75 women with breast cancer who were prescribed GLP-1 agonists. Almost 80% of the participants had diabetes, and 60% were undergoing hormone therapy. At the beginning of the study, the median body mass index (BMI) of the group was 34 kg/m². After 12 months, the women had lost an average of 6.2 kg, or about 5% of their total body weight.

While this is a meaningful reduction, it is notably less than the weight loss observed in phase 3 trials involving patients without cancer, where participants typically lose twice as much weight. Another recent study found similar results, with breast cancer patients experiencing a modest 4.34% reduction in BMI after 12 months on Wegovy, compared to a 14% reduction seen in the general population. Zepbound, on the other hand, was associated with a small overall increase in BMI for cancer patients, while in non-cancer patients, it resulted in a significant 15% BMI reduction.

These findings indicate that GLP-1 agonists may not be as effective in cancer patients, particularly those on hormone therapies. It is unclear why this discrepancy exists, but it could be related to the metabolic changes induced by cancer treatments, such as steroids and hormone therapies, which can increase appetite and cause weight gain. Some treatments may also slow metabolism or induce fatigue, making exercise more difficult.

Future Research and Safety Concerns

There is still much to learn about how GLP-1 agonists work in cancer patients. Some oncologists, like Dr. Iyengar, speculate that higher doses might be necessary to achieve the same weight loss results seen in the general population. Others, like Dr. Gallagher, have found the newer agents, including Wegovy and Zepbound, to be just as effective in their cancer patients as they are in the general population.

As for safety, both Wegovy and Zepbound carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma, though recent studies suggest GLP-1 agonists do not increase the risk of thyroid cancer. These drugs are contraindicated in patients with a personal or family history of thyroid cancer and in those with multiple endocrine neoplasia syndrome type 2. While neither Dr. Iyengar nor Dr. Gallagher have seen any secondary tumors in their patients, they remain cautious and follow labeling recommendations.

Looking ahead, pharmaceutical companies are interested in pursuing cancer-specific indications for GLP-1 agonists. Both Dr. Iyengar and Dr. Gallagher’s institutions are in talks with drug manufacturers to participate in global phase 3 trials aimed at assessing the efficacy and safety of these drugs in oncology settings.

“I think there’s potential here,” said Dr. Iyengar. “These drugs do a lot that we don’t fully understand yet, but from what we’ve seen so far, they seem to be safe.” He adds that while the safety profile is promising, the key challenge will be demonstrating a significant, lasting benefit in cancer patients, enough to warrant FDA approval.

“If we can prove that these drugs help patients achieve durable weight loss and improve cancer outcomes, it could be one of the most significant advancements in both medicine and oncology, particularly given the overlapping epidemics of obesity and cancer,” said Dr. Iyengar.