Could Popular Weight Loss Drugs Help Prevent Cancer?

Dr. Diane Reidy-Lagunes:

You probably heard about a new class of weight loss drugs like Ozempic, Mounjaro and Wegovy, well known for helping people shed pounds quickly. But did you know that these drugs may also play a role in lowering your cancer risk? A new study suggests that indeed, maybe it can. So how do these drugs work? And if you're facing a cancer diagnosis, can they help or hurt you? Let's talk about it.

Hello, I'm Dr. Diane Reidy-Lagunes from Memorial Sloan Kettering Cancer Center, and welcome to Cancer Straight Talk. We're bringing together national experts and patients fighting these diseases to have evidence-based conversations. Our mission is to educate and empower you and your family members to make the right decisions and live happier and healthier lives. For more information on the topics discussed here, or to send us your questions, please visit us at mskcc.org/podcast.

Today we are joined by friend of the pod, Dr. Neil Iyengar. Neil's a breast medical oncologist, and MSK's leading researcher on diet, metabolism, and cancer. He previously joined us on the pod for episode 11, where we discussed diet trends, exercise, and the relationship between fat tissue and cancer. Today, we'll learn about the relationship between weight loss drugs, the so-called GLP-1 medications, and cancer risk. Neil, thanks so much for joining us again and welcome back to the show.

Dr. Neil Iyengar:

Thanks so much, Diane. It's a pleasure to be back.

Dr. Diane Reidy-Lagunes:

We love having you. So this latest study sounds very promising. And to start out, for those who may not be familiar with this class of medications, can you explain to us how they may control diabetes and specifically weight loss?

Dr. Neil Iyengar:

Sure. So this is an exciting class of medications that was originally developed for the treatment of diabetes, and several of these drugs are now indicated for weight loss. And you can think of these drugs as medications that help mimic some of the hormones in our body that essentially put our bodies into a post-meal state. What I mean by a post-meal state, is that we see increases in certain hormones that tell our brains that we're no longer hungry. We also see increases in certain hormones that help to store fat rather than release fat, and we see increases in insulin sensitivity, which really helps regulate our glucose or sugar metabolism.

When you put all of this together, you get a lot of effects that are helpful, both in terms of reducing blood glucose levels, improving diabetes, as well as improving our body's ability to store fat and improving our ability to prevent ourselves from eating excess calories– both because we're feeling satiated and full, but also because our body is now in a state of efficient energy storage. In the end, this leads to improvements for people with diabetes and it improves and accelerates weight loss and specifically fat mass loss.

Dr. Diane Reidy-Lagunes:

We know there are at least 13 cancers that are correlated to obesity. In fact, many people equate obesity and that rising epidemic to tobacco and how that increased the risk of cancer. Can you share with us the results of this study and why it's so exciting?

Dr. Neil Iyengar:

The investigators were able to look at patients who were prescribed one of these medications, a GLP-1 agonist, and subsequently the development or the diagnosis of various cancers. As you mentioned, we know that there are at least 13 cancers that are associated with obesity. So the investigators specifically looked at those cancers and found that the risk or the incidence of developing 10 of those obesity-related cancers was significantly reduced. 

Dr. Diane Reidy-Lagunes:

And Neil, what are those 10 cancers that they thought were protective when you got this class of medications?

Dr. Neil Iyengar:

So the study showed that people with a diagnosis of type 2 diabetes who were treated with a GLP-1 agonist weight loss drug had lower chances of developing 10 different obesity-related cancers. This included lower risks of cancers of the gallbladder, pancreas, liver, ovaries, colorectal cancer, multiple myeloma, meningioma, esophagus, endometrial cancer, and kidney cancer.

Dr. Diane Reidy-Lagunes:

Do we know what it is? Is it the drug? Is it the weight loss itself? Could there be other mechanisms? 

Dr. Neil Iyengar:

So there's a lot, as I mentioned earlier, about this new class of drugs that we don't quite yet know. When it comes to the potential cancer prevention effects, it's still not exactly clear in terms of how these drugs may help reduce the risk of cancer. I think the clearest or the most straightforward explanation is that they're so effective at causing weight loss, and we know that weight loss is an effective way of reducing the risk of several types of cancers. So one school of thought is that just by virtue of reducing weight, these drugs may be reducing cancer risk mainly through that mechanism. In other words, it doesn't matter how you lose weight, as long as you do lose weight, that translates to a cancer prevention benefit. And I suspect that that's the real reason that we're seeing that reduction in 10 different obesity-related cancers, with these medications.

There may be other mechanisms. We know that these drugs not only induce fat loss, but they alter the way that our fat cells work. And there are studies going on right now to try to better understand what some of these biological changes are. Are there immune changes within the fat tissue? Are there other hormonal changes within the fat tissue that lower the risk of cancer, specifically those cancers that develop within fat tissue, like breast cancer or prostate cancer, for example? But I'd say the jury's still out on that one. I think the driving reason why we're seeing a potential prevention effect with this class of drugs is that it's simply so effective at inducing weight loss. 

Dr. Diane Reidy-Lagunes:

What about people who are already diagnosed with cancer? Can Ozempic and these similar weight loss drugs help them?

Dr. Neil Iyengar:

Yeah, such an important question, and there we have far less data. We recently presented data at the American Society of Clinical Oncology, where we studied approximately 70 patients who were prescribed these weight loss medications after breast cancer diagnosis. Some were on hormone therapy, some were completed or finished with their therapy. And what we found was that the amount of weight loss was surprisingly less than what has been reported in non-cancer populations or in patients who don't have cancer.

What we don't know is, could that be because of the dosage of the medication that was used in this cohort? Could it be because of a potential interaction between the cancer therapy, like hormone therapy, and these medications? Or it could potentially be because of the study design? This is a retrospective observational study.

So the bottom line is that we need more data in this space, and there are potential concerns about overlapping these medications with different types of cancer therapies that might exacerbate some of the side effects. We don't know ultimately what the long-term effects are on the efficacy of cancer therapy, though I would hypothesize it's probably a positive benefit for some cancers based on what we're seeing in the pre-diagnosis space. But this is an area where there's a lot of investigation going on right now, and we simply need more data.

Dr. Diane Reidy-Lagunes:

Okay. Jury's still out on that one. I think there's a lot of conversation on about, what if you stop it? Most of the data suggests that a lot of the benefit you get from the drug tends to go away when the drug is stopped. Do you worry that the risk of cancer may go back up again, or is that too hard to know?

Dr. Neil Iyengar:

This is also really important because we know from the diet and exercise world that yo-yo diets, or weight going up and down, can actually be harmful for cancer risk because this causes quite a degree of confusion, if you will. The body becomes really perpetuated between cycles of high insulin and low insulin and so forth, and this can induce inflammation and DNA damage. But fortunately that type of yo-yo-ing is more prominent with fad diets, whereas these medications tend to induce longer periods of weight loss, more successful periods of weight loss. If a person does stop the medication and starts to gain the weight back, from what we are seeing so far, the weight gain doesn't appear to be as sudden or quick as with some types of fad diets or yo-yo diets.

But I think it really comes down to the fact that we can't ignore lifestyle changes. We really need to work on consuming a healthy diet, leading a healthy active lifestyle, even while on these medications. And I think of these medications as a tool. It can be incredibly hard to start the weight loss journey, especially if a person has been struggling for a long time. This provides a really nice catalyst to get a person going, induce that initial weight loss. I think it can be mentally motivating when you see that large degree of weight loss, but also physically speaking, it can be very helpful too because it builds that momentum for weight loss once a person comes off the medication. That healthy weight and body composition can potentially be maintained by those lifestyle changes that a person made when they started the drug. So that's why I always encourage starting off with lifestyle modification, then adding these medications if a person needs them, and to think of them as a tool but not an answer to a healthy lifestyle.

Dr. Diane Reidy-Lagunes:

Absolutely. And to share, a friend of mine did just do that. She was having trouble doing exercises in part because of arthritis and plantar fasciitis, then she went on the medications and that all went away. So thankfully she was able to maintain more of the lifestyle that she wanted with the weight off.

Dr. Neil Iyengar:

I love that story. These kinds of stories are increasingly common experience with these medications and it's so helpful to be able to shed some of those problems that are barriers to starting an exercise program. I've certainly had patients and friends tell me that, mentally speaking, they are just less attracted to food. And after coming off the medication, that effect seems to linger. People have, over the course of their treatment, changed the way that they approach food, their philosophy towards food, and I think that's also a really helpful effect. I've always talked about mindful eating – we think about what we're putting in our bodies – and I think that these medications can be very helpful in terms of serving as a catalyst to promote mindful eating.

Dr. Diane Reidy-Lagunes:

Absolutely. Anything that worries you about taking the medication in terms of side effects and/or the rare but potential risks of a cancer, thyroid cancer in particular?

Dr. Neil Iyengar:

There's still a lot, when it comes to these medications and cancer, that we don't yet know. The side effect profile – while these medications are generally well tolerated and they are safe medications for the most part – there are potential interactions that we don't have enough data for, with regard to making side effects worse from cancer therapies, or making side effects worse from the weight loss medications, or perhaps new interactions that we simply haven't discovered yet. And this is why we do need more studies, more clinical trials, that are specifically studying these promising medications in people that have been diagnosed with cancer. I tell folks that if you are on cancer therapy, it's really important that you speak to your oncologist before starting a weight loss medication.

You mentioned the rare risk of a type of thyroid cancer. I think the risk is really quite low, and there's still some debate in the field about whether this is truly a risk or something that was observed in some of the trials that may be unrelated. I think, for now, we need to be careful and cautious and assume that it is indeed a risk, a rare risk. But this goes back to really understanding what your individual risks are and the risk-benefit ratio of these medications for your individual situation, in consultation with your oncologist.

Dr. Diane Reidy-Lagunes:

Absolutely. So again, just to emphasize, as a GI oncologist, I look at this data and it's early. It's what we call retrospective. Like you said, there's a lot of potential flaws with this type of data when we analyze it, and more studies would have to confirm. But taking a quick look, some of the deadliest diseases I care for, like colon and pancreas cancer, had a marked reduction in people who were on these therapies.

Could you talk to us a little bit about breast cancer, since that's your world and your expertise, and if we saw that same reduction in preventing breast cancers when folks were on this treatment?

Dr. Neil Iyengar:

Absolutely. While this recent study showing a potential prevention effect with weight loss drugs against cancer is very promising, as you mentioned, it is not a definitive study. There are questions that remain. I mentioned earlier that the study found that the risk of 10 obesity-related cancers, including colon cancer, was significantly lowered with the weight loss medications. But breast cancer was not on that list, and I think there are several potential explanations for this.

The first is, I do want to caution people a little bit about this study. While I'm very, grateful that the investigators conducted this study, we do have to understand that there are some limitations here. We talked about the retrospective nature of the study. I'll just also point out that the dose of these weight loss medications varies a little bit. There's a different dose for treating diabetes versus treating weight loss. The length of time that you spend on the medication, how adherent a person is to the medication, all of these things might be critical because we are learning that for breast cancer risk, the timing of when a person develops obesity, when a person loses weight, how much their weight fluctuates, all of this seems to contribute to the risk of developing breast cancer.

And that's where we really need to start understanding: Is there an ideal window for when to use these weight loss medications for cancer prevention? I suspect we will see a breast cancer prevention effect if we use these tools in a way that's scientifically guided and that's appropriate for the individual.

Dr. Diane Reidy-Lagunes:

Totally. I'd like to end to go back to our listeners who are being treated for active cancer. And although the jury is out in seeing if this class of medications can help them, your research suggests that in fact, there are things we can do to help treat our cancer that has to do with modification to how we eat and how we live. Can you talk to us about that and what you recommend for patients?

Dr. Neil Iyengar:

Absolutely. I can give you 3 key things that I would recommend to most people. One is, maintain a healthy weight. That sounds obvious, but how we do that, of course, is a lot more complex. One of the biggest pieces of advice I could give you is that the diet is really, really important. Specifically, I would recommend eating a plant-forward diet where at least 80% of your diet or food intake comes from minimally processed, whole foods. If you do eat meat, limit it to about 20% and preferably lean, non-red and non-processed meats.

The second point is that we get far too little fiber in the Western diet, and we find that fiber has so many protective qualities, both for cardiovascular health and for our microbiomes, cancer prevention, as well. The American Institute of Cancer Research recommends at least 30 grams a day of fiber. That's a lot of fiber, but I recommend setting that goal, and doing what you can to get to those 30 grams. If you can get to 20 grams a day of fiber, you're doing very well.

And then the third point really is to maintain an active lifestyle, engaging in about 150 minutes per week of moderate intensity aerobic exercise and 2 days a week strength training or resistance training. That can really help maintain that healthy weight and healthy lifestyle. 

Dr. Diane Reidy-Lagunes:

Great stuff. Neil, any final thoughts?

Dr. Neil Iyengar:

We talked a little bit about what we know and what we don't know, but I think if you're a person who’s been struggling with body weight for a long time, and you've really tried diet and exercise or even certain medications, this is a topic that you should bring up with your oncologist. And if you haven't been diagnosed with cancer, a topic that you should bring up with your primary care physician. With the right timing of these medications and with the right lifestyle modifications in combination with these medications, I think this is an exciting new era where we really now might be able to make a dent in the obesity-cancer epidemic that's going on. 

Dr. Diane Reidy-Lagunes:

I agree. Neil, our listeners and I always love having you on the pod, and I'm so grateful for your time and expertise. Like always, I learned a lot.

Dr. Neil Iyengar:

Thanks so much for having me on. It's always such a pleasure to have a conversation with you, Diane.

Dr. Diane Reidy-Lagunes:

Thank you for listening to Cancer Straight Talk from Memorial Sloan Kettering Cancer Center. For more information or to send us your questions, please visit us at mskcc.org/podcast. Help others find this helpful resource by rating and reviewing it on Apple Podcasts or wherever you listen. Any products mentioned on the show are not official endorsements by Memorial Sloan Kettering. These episodes are for you but are not intended to be a medical substitute. Please remember to consult your doctor with any questions you have regarding medical conditions. I'm Dr. Diane Reidy-Lagunes. Onward and upward.