FOCUS-GLP-1 drugs may have a beneficial effect across many types of cancer

Research presented at the American Society of Clinical Oncology meeting suggests that popular GLP-1 weight loss and diabetes drugs may lower cancer risks and improve treatment outcomes in patients.

A growing body of evidence suggests that popular GLP-1 drugs, widely used for weight loss and diabetes, can provide protection against many types of cancer.

More ​than two dozen studies presented over the past few days at the American Society of Clinical Oncology meeting ​in Chicago found that patients taking the drugs showed lower risks of developing cancer and ‌disease ​progression, better survival, and improved responses to some treatments, compared with people who were not taking the GLP-1s. The studies included analyses of clinical records and real-world databases tracking patients taking Novo Nordisk's Wegovy or Ozempic, Eli Lilly's Zepbound or Mounjaro, or older GLP-1 treatments.

The studies were not designed to show how or why GLP-1 use might affect cancer treatment. But researchers believe by reducing inflammation, regulating ‌insulin signaling and possibly engaging directly with tumor biology, they may contribute to a protective effect in cancer patients. “Chronic inflammation is a fundamental biological pathway involved in the development and progression of many cancers,” said Dr. Elizabeth Susan McDonald of the University of Pennsylvania.

McDonald on Tuesday reported on a study of 110,000 women, showing those who took GLP-1 medications were up to 35% less likely to develop breast cancer than those who did not. While obesity itself is a known risk factor for certain cancers, the anti-inflammatory effects of GLP-1s will likely prove ‌to have a role in cancer prevention, McDonald said.

BENEFITS ACROSS CANCER STAGES AND TUMOR TYPES GLP-1 drugs include semaglutide, the active ingredient in Wegovy, Ozempic and Rybelsus; tirzepatide, sold as Mounjaro and Zepbound, as well as Lilly's Trulicity, or dulaglutide, and Novo's ‌older liraglutide, sold as Saxenda and Victoza.

Some of the strongest signals of benefit came from a study of more than 12,000 patients that showed GLP-1 use was associated with markedly lower odds of cancers advancing to metastatic disease, particularly in lung, breast, colorectal and liver cancers. People with those cancers who took liraglutide, pramlintide, dulaglutide, tirzepatide, lixisenatide, or semaglutide were 38% to 50% less likely to see the disease spread than people who took drugs from a different class of diabetes medicines known as gliptins.

Reduced cancer incidence, longer survival, and fewer metastases were also seen with GLP-1 use in patients with endometrial, bladder and prostate cancers, as well as in ⁠those with small intestine ​neoplasms and blood cancers, multiple studies found. A separate analysis of patients treated ⁠at U.S. community oncology practices found GLP-1 use was associated with significantly better overall survival across six tumor types - breast, prostate, colorectal, lung, liver and kidney - with a roughly one-third reduction in the risk of death.

Researchers also reported that cancer patients receiving immunotherapies such as Merck's Keytruda and Bristol Myers Squibb's Opdivo or Yervoy ⁠appeared to fare better when they were taking GLP-1 drugs, suggesting a possible interaction with the immune system. GLP-1 users with type 2 diabetes and stage 3 kidney disease had substantially lower mortality and lower rates of several malignancies, particularly lung, colorectal, and hepatocellular cancers, than non-users.

While GLP-1 medications carry a warning ​regarding a possible association with a type of thyroid cancer based on rodent studies, researchers say the recent findings point to a potential beneficial class effect across tumor types, rather than benefits confined to a small subset of cancers. The ⁠drugs, originally designed to treat diabetes and found to promote weight loss, have also shown benefits for heart risks, sleep apnea and alcohol and substance abuse.

“These drugs have never been just glucose-lowering agents,” Dr. Marcin Chwistek of the Fox Chase Cancer Center in Philadelphia said at an ASCO press briefing. LIMITING FACTORS

Researchers cautioned that nearly all ⁠of ​the data presented were from observational studies, raising the risk of confounding factors. Patients prescribed GLP-1 drugs may differ in important ways, including overall health, access to care and concurrent treatments, that could influence outcomes. While the various studies tried to account for those differences, none can prove the drugs improve cancer outcomes. Experts said trials in which GLP-1s are added to standard treatment in some cancer patients but not others are needed to establish clear anti-cancer benefits. Some trials are already being planned.

The apparent cancer benefits were not clearly ⁠tied to the drugs' weight-loss effects, suggesting that alone does not explain the findings. A seven-year study with nearly 120,000 participants found GLP-1s were associated with lower rates of new prostate cancer diagnoses in high-risk men, compared to drugs such as Merck's Propecia and ⁠GSK's Avodart, which are used to shrink enlarged prostate glands.

GLP-1 users had ⁠a "very small" reduction in body weight at one year, said Dr. Colton Jones of the University of Texas San Antonio Mays Cancer Center who presented the study at ASCO. "We hypothesize that both weight loss and a direct anti-cancer effect and anti-inflammatory effect may be driving the associations observed in our study,” Jones said.

ASCO expert Chwistek said anti-inflammatory and immune-modulating properties have long suggested broader ‌effects of GLP-1s. Referring to one of the largest ‌studies, Chwistek said: "What's new here is the consistency across tumor types, and data this large and this consistent warrant a prospective ​randomized trial."