Diabetes drugs such as Ozempic may reduce the risk of 10 cancers

Obesity and type 2 diabetes (T2D) are common conditions that can pose health risks to people. Approaches to diabetes treatment may play a role in future health risks, and researchers are beginning to connect the dots in this area.

A study published in JAMA Network Open compared groups of people with T2D receiving three types of treatment: glucagon-like peptide receptor agonists (GLP-1RA), insulin, and metformin.

The study results showed that participants taking GLP-1RA had a significantly reduced risk of developing 10 of 13 obesity-related cancers compared with participants taking insulin.

This suggests that GLP-1RA may help prevent some obesity-related cancers.

Obesity as a risk factor for cancer

Being obese or overweight can increase your risk of developing certain conditions. For example, being obese or overweight can increase your chances of developing thyroid, pancreatic, colon, breast, or liver cancer. In particular, there are thirteen types of cancer that are more likely to occur if you are overweight or obese.

Dr. Wael Harb, a board-certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers in Orange County, California, who was not involved in the study, explained how obesity is linked to cancer:

"Obesity is a well-established risk factor for several types of cancer. Mechanisms linking obesity to cancer include chronic inflammation, insulin resistance, elevated levels of insulin and insulin-like growth factors, altered levels of sex hormones and adipokines. These factors may promote tumor development and progression."

"Being overweight also affects the body's immune response and can create an environment favorable for cancer growth. Specific cancers associated with obesity include colorectal, breast, endometrial, kidney, and pancreatic cancers, among others."

Doctors can help reduce the risk of obesity-related cancer by talking to patients about ways to eat a healthy diet and increase physical activity to maintain a healthy weight. This may also include providing appropriate cancer screenings for people at higher risk of developing obesity-related cancers.

Researchers are also interested in tools and interventions that can help people at increased risk of obesity-related cancers. The authors of this study wanted to examine how interventions for T2D affect the risk of obesity-related cancers.

GLP-1RA use may reduce risk of certain obesity-related cancers

The study was a retrospective observational study. To gather information from a large sample, the researchers used anonymized electronic health records. Their analysis included data from more than 1.6 million people.

All participants had T2DM and no history of any of the 13 obesity-related cancers. All participants also received one of three types of diabetes medication:

• Glucagon-like peptide receptor agonists (GLP-1RA), such as Ozempic.
• Insulin.
• Metformin.

Over a fifteen-year follow-up period, the researchers looked at the incidence of each of thirteen obesity-related cancers among the participants. In their analysis, the researchers found that participants who were prescribed GLP-1RAs had a lower risk of ten of the thirteen obesity-related cancers compared to those prescribed insulin. This included a reduced risk of gallbladder, pancreatic, ovarian, colon, and esophageal cancers.

The risks associated with stomach cancer in this comparison had a hazard ratio of less than one for participants taking GLP-1RA compared with insulin users, but this did not reach statistical significance. The researchers found no association between GLP-1RA use and a reduced risk of breast or thyroid cancer compared with insulin.

The researchers then compared the risks for people taking GLP-1RA with those taking metformin. The risk of colon and gallbladder cancer was reduced for participants taking GLP-1RA, but not to statistically significant levels, compared with those taking metformin.

Overall, the researchers found that compared with metformin users, GLP-1RA users had no reduced risk for any type of cancer and also had an increased risk of kidney cancer.

Dr. Harb noted the following clinical implications of the data:

"The potential clinical implications of these findings are significant. If GLP-1RAs do protect against certain obesity-related cancers, their use may be prioritized in the management of patients with T2DM who are at high risk for these cancers. This could result in the dual benefit of improved glycemic control and reduced cancer risk."

"For example, the study found that GLP-1RAs were associated with a hazard ratio of 0.35 for gallbladder cancer, 0.41 for pancreatic cancer, and 0.54 for colon cancer compared with insulin, indicating a significant protective effect. Furthermore, these findings may stimulate further investigation into the mechanisms by which GLP-1RAs exert these protective effects, which could potentially lead to the development of new therapeutic strategies."

Limitations of the study and further research

This study supports the idea that GLP-1RAs may help reduce the risk of cancer. However, it is important to consider the limitations of the study. First, due to the nature of the study and the use of electronic medical records, there is a risk of diagnostic errors, bias, and confounding. Electronic medical records also include data that was self-reported by participants, which may be inaccurate.

The study can’t prove causation and didn’t allow the researchers to control for variables after the participants were first prescribed a prescription. The researchers also couldn’t identify individual patient data, meaning they couldn’t, for example, “link risk reduction to the degree of weight loss.” They also lacked data on medication adherence, which could have affected the study’s results. Finally, they couldn’t explicitly control for participants’ insurance type or health care use.

The researchers note that future studies could confirm their findings using other electronic health record databases and analytics. Further research is needed to understand potential risks of GLP-1RA, such as a possible increase in the risk of thyroid cancer.

Dr. Anton Bilchik, a surgical oncologist, chief medical officer and director of the Gastrointestinal and Hepatobiliary Diseases Program at Providence St. John's Cancer Institute in Santa Monica, California, who was not involved in the study, offered the following words of caution regarding the study's findings:

"This study has a fairly long follow-up period and includes a large number of patients. Although it shows a reduction in several obesity-related cancers, it remains unclear whether this is a direct effect of the GLP-1 drugs in preventing cancer or whether the reduction is due to weight loss as a result of the drug. This requires further clarification."

"The study also demonstrates how obesity increases the risk of several types of cancer and that exercise, diet and weight loss are important factors in reducing risk. GLP-1 supplements are important as an adjunct to weight loss and therefore cancer prevention, but should not be seen as a substitute for what we already know about the importance of reducing cancer risk."