Weight loss injections and cancer: 6 questions, answered

Most people know that losing weight has numerous benefits, but making major lifestyle changes can be extremely difficult. For example, obese people are often at risk for injuries when they start a new exercise routine, which can set them back or ultimately cause them to give up on it. As a result, more and more people have been turning to weight loss medications for help.

In the last couple of years, a new class of weight-loss injection drugs called GLP-1 agonists like semaglutide, tirzepatide, liraglutide and dulaglutide has made headlines for their promise to help people lose weight. The drugs go by several different brand names, and more are being approved all the time. But what are they, how do they work and are there things current cancer patients should be aware of if they’re considering these drugs?

For answers to these questions, we talked to endocrine neoplasia and hormonal disorders specialist Sonali Thosani, M.D.

How do these drugs work, and how are they different from previous weight loss drugs?

Previous weight loss drugs worked in a few different ways. Some suppressed appetite and made you feel fuller longer, but these could only be used for a limited time due to the side effects. Others inhibited fat absorption, but were hard to tolerate for many patients because they caused gastrointestinal issues.

This new class of drugs, the GLP-1 agonists, has been used for diabetes treatment since 2005, but they only have gotten approval for obesity treatment in the last decade. They work by slowing down gastric emptying. This makes patients feel fuller longer, helping them eat less. They also help balance blood sugars after eating by stimulating insulin secretion and inhibiting glucagon secretion.

Studies have shown that patients can lose up to 20% of their body weight with GLP-1 agonists. That makes these drugs comparable to surgical options, like gastric sleeve surgeries. However, they also have some side effects, with many patients experiencing nausea, vomiting and diarrhea. There have also been some recent reports that they might be linked to gastroparesis in some patients. This is a paralysis of the stomach that can be debilitating and hard to treat.

What’s also interesting about these drugs is that GLP-1 is a neuropeptide. This means it’s made in the neuronal cells in the brain and released in the hypothalamus, which controls several metabolic and cardiovascular functions. So, it will be interesting to see what we continue to learn about how these drugs work and what the long-term effects might be on other organ systems.

Can weight loss injections decrease your cancer risk?

This is a more complicated question than it seems because obesity is so closely associated with increased cancer risk. There are really two questions here:

• Do the drugs themselves decrease cancer risk?
• Does their ability to decrease obesity result in a lowered cancer risk?

There is significant evidence that the answer to the second question is yes, with the caveat that patients should know that these drugs aren’t meant to be taken forever. Many people take GLP-1 agonists or other weight loss medication, they lose weight, they go off the drugs and then they gain the weight back. That’s not going to help lower long-term cancer risk.

Where these types of drugs can be helpful is that many obese people have a hard time making healthy lifestyle changes because it’s very difficult for them to exercise. If taking these drugs for a limited amount of time can help some lose weight quickly so they can get on an exercise plan they can stick to, then that’s helping lower cancer risk long-term. But it all comes back to the person making and sticking to those lifestyle changes, even after they stop taking the drugs. If they can do that, then you’re probably seeing a net positive about long-term cancer risk or other long-term health risks.

As for whether the drugs themselves reduce cancer risk, it’s too early to say for sure. But there is some evidence that GLP-1 agonists like semaglutide may decrease cancer risk beyond just their ability to help people lose weight. A study published early this year showed that patients with diabetes who used weight loss injections were less likely to have colorectal cancer compared to patients on other diabetes drugs, regardless of whether the patients were overweight.

Are there concerns that weight loss injections could increase cancer risk?

There was an early study a couple of years ago that indicated a possible link to thyroid cancer, but that study had some limitations, and subsequent studies have shown that there is likely not a link there. The European Medical Agency even announced that they did not find a causal link after a months-long review of the data.

There has also been some concern that some of the side effects could increase the risk of pancreatic cancer, but so far, studies have not shown that to be the case.

If cancer isn’t a major concern, are there other concerns about these drugs?

There’s always a bit of wariness when a new class of drugs comes to market because we’ve seen several times where promising drugs came to market for weight loss and then they’ve had to be pulled back, due to safety concerns. What’s unique about GLP-1 agonists compared to other weight loss drugs is that we already have a lot of experience with them in patients with diabetes. We also know from the published data that these drugs have heart health benefits; this sets them apart from other weight loss drugs currently on the market.

The primary concern is the availability of these drugs for the patients who need them. They’re expensive, and it’s been hard to get insurers to cover them, even when a patient has a clear indication for them. And there are celebrities and influencers using them who don’t have indications for their use, adding to a national shortage and making them even harder to get.

And the gastroparesis issue is not a small thing. Doctors need to be selective when deciding whether a patient meets the criteria for these drugs because gastroparesis can be very difficult to manage. Guidelines from anesthesia and surgical societies recommend holding the weekly formulations of these drugs for at least a week before surgery, so careful planning is required if a patient is using these therapies.

Are there concerns about these drugs for people who have already had cancer?

There are a couple of things to note for cancer patients, which is why it is always very important to discuss these things with your care team.

We generally avoid GLP-1 agonists for pancreatic cancer patients, for example, because these patients are already at high risk for pancreatitis, and these drugs do carry some potential risk for that. We are also cautious about using these drugs if you’re on active cancer therapy and experiencing side effects such as nausea and vomiting; GLP-1 agonist therapy can sometimes worsen those.

These drugs cause dramatic weight loss, some of which is also a significant muscle mass loss. So, we need to carefully monitor their use in patients who are on active chemotherapy, as sarcopenia and weight loss can make it harder for patients to tolerate chemotherapy.

Are there alternatives to weight loss drugs that people should consider?

I think bariatric surgery is underutilized. And, of the 20 million adults in the US who suffer from severe obesity, less than 1% will undergo bariatric surgery annually. There was a study presented at a national meeting looking at the role of bariatric surgery in patients with obesity and the impact on cancer prevention, and it found a marked decrease in cancer diagnoses in patients with obesity who underwent bariatric surgery compared to those who didn't. This was really the first study to address this question, and I think this exciting new area will have more studies coming out in the next 10 to 15 years.

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