Q: I’m worried that GLP-1s are bad for my gut. Should I avoid them altogether for this reason?
A: In the original clinical trials of GLP-1 medications for weight loss, the most common side effects were gastrointestinal, including nausea, vomiting, and constipation. Ask almost anyone who’s been on one, and they’ll probably tell you that they’ve had some GI issues — even if very mild.
So you might be surprised that as a gastroenterologist, when my patients tell me they’re considering starting a GLP-1 (the class of drug that includes Ozempic, Wegovy, and Zepbound, among others), my answer is often highly enthusiastic: Do. It.
We hear all the time about the weight loss or heart health benefits of GLP-1s, but as a scientist who studies GLP-1 and the stomach in my own laboratory, I’ve seen firsthand how powerful and beneficial they can be for gut health. The GI effects of GLP-1s that I wish more people talked about? Randomized controlled trials have found that they can, in some cases, improve outcomes for people with fatty liver disease and fibrosis — or liver scarring — which previously no drugs could reliably achieve.
GLP-1s are also associated with a lower risk of stomach ulcers, according to research I conducted with my colleagues and — here’s a big one — they’re linked to lower odds of colorectal cancer. Many of these potential associated benefits are unrelated to weight loss, although the weight loss alone can start a cascade of wins.
For example, one of my patients who started a GLP-1 lost about 20 pounds after six months. Losing that 20 pounds helped her knees, which had been aching all the time, and allowed her to begin exercising regularly. She began walking daily and then, before long, joined a Zumba class. This would have been unheard of for her before taking a GLP-1. Now, even though her weight has remained steady, she’s a healthier person because she stays active, something that lowers the risk of cancer and heart disease regardless of her weight.
That doesn’t mean I downplay the GI issues, rather in my practice, I anticipate them and make a proactive plan. With each patient, I have an honest discussion about the possibility of unwanted side effects, including the possibility of more serious, although rare, complications such as pancreatitis.
Let’s be real: The majority of people taking GLP-1s do experience symptoms like nausea or constipation. However, in most cases, these symptoms are mild to moderate and transient: Fewer than 5% of people stop treatment because of GI symptoms. So if someone wants to stick with their GLP-1, I like to help give them every chance I can. And with a pill version of Wegovy now available, they’re going to become increasingly accessible.
Everyone interested in GLP-1s should have that clear-minded discussion with their own physician who knows their own medical history and goals. To help start that conversation, here are some of the most common questions I get:
What exactly are GLP-1 medications doing to my gut?
You’ve probably heard that GLP-1, or glucagonlike peptide 1, is a hormone produced by the body that is involved in hunger signaling. But GLP-1 medications do so much more than this. For instance, they suppress stomach acid production and fortify the protective mucus layer along the stomach’s lining, which is at least partly how scientists like myself hypothesize they may help reduce the risk of ulcers. Perhaps most evident to anyone taking them is that GLP-1s slow the stomach down. As a result, food sits inside longer before it gets emptied into the small intestine, and that can create an uncomfortable sense of fullness and queasiness. (Hello, Ozempic burps!) A similar slowing occurs in the colon. Because one of the colon’s primary jobs is to absorb water, the longer the waste sits there, the drier and harder it becomes. Hence, constipation.
We still have much to learn about GLP-1’s other effects on the gut and body. How GLP-1 medication influence our microbiome is an emerging area of research, but some limited studies in humans suggest that they may influence the production of beneficial bacterial metabolites. They also appear to help reduce chronic inflammation, which plays a big role in multiple diseases.
How can I treat the unwanted side effects?
You should explore possible treatments with your physician, who can make tailored recommendations. The goal isn’t for you to “suffer through” therapy with GLP-1 in the name of good health, but to make taking a GLP-1 drug as sustainable as possible. I tell my patients when starting these drugs to expect side effects and plan for them. And no, GI symptoms like nausea are not what drives weight loss, so don’t hold back seeking help.
Let your hunger cues guide you
Contrary to how many of us eat otherwise, when taking a GLP-1 it’s important to try to eat only when actually hungry, eat slowly, and respond to your body’s cues saying you’re full. It’s common for people to eat smaller portions than they’re used to, but still feel satisfied.
Be proactive about bowel issues
Anyone who struggles with their bowel movements at baseline, speak up now: We need to be especially proactive. Sometimes it’s as simple as starting a daily fiber supplement, which can be helpful for diarrhea or constipation (both are possible with GLP-1s). In the case of constipation, over-the-counter laxatives like a capful of powdered polyethylene glycol (like in Miralax) can help, while for diarrhea, loperamide (like in Imodium) can be great. But don’t give up if these feel inadequate — there are also several prescription medications that can help get your colon back on track.
Try OTC remedies for nausea and heartburn
For nausea, sometimes the fix can be to simply lower the dose of the GLP-1 you’re taking, although there are medications that can help. Over-the-counter remedies like bismuth subsalicylate (like in Pepto-Bismol), dimenhydrinate (like in Dramamine), or ginger tea can provide quick relief. If these are insufficient, your doctor may consider prescription antinausea medications. Because of the delay in stomach emptying, heartburn can also show up, but over-the-counter treatments like histamine-2 blockers (like Pepcid AC and Zantac 360) can help.
Who is more likely to experience side effects?
In real-world studies of people taking these medications, men appear to have half the risk of experiencing GI side effects as women. The most important advice to avoid side effects is to start on a low dose and increase slowly.
Are certain GLP-1s more likely to cause side effects?
Head-to-head trials comparing semaglutide (Ozempic, Wegovy) with liraglutide (Victoza, Saxenda) show broadly similar GI side effects overall, though results vary somewhat by study and dose. The good news is that major trials have found that these side effects were more common in the first few days or weeks of starting treatment, when they peaked, but then tended to subside. So I tell my patients that even if they experience GI symptoms initially, there’s a good chance they’ll get better.
What I want my patients to know
GLP-1 drugs are often spoken of as weight loss tools but, to me, that really misses the point. Obesity is a chronic, inflammatory disease that drives up the risk of heart disease, Type 2 diabetes, and certain cancers. Using a medication to treat a medical condition is not a moral failing — as some of my patients have been made to feel. There are fewer more powerful steps someone can take for their health than to reduce that constant state of inflammation, and as a doctor, I will always find that worth celebrating and supporting.
Trisha Pasricha is an assistant professor of medicine at Harvard Medical School and author of the forthcoming book “You’ve Been Pooping All Wrong.”
