Oh, oh, oh, shh*t!
GLP-1 agonist weight loss drugs and GI effects
GLP-1 agonists were not all over the news when I first started in private practice. I had about two patients over 6 months who would come in and tell me that they had altered bowel habits because of Ozempic or Wegovy. It's possible that everyone else was simply not admitting to taking these weight-loss injections. Almost two years later, I’d say 1 in every 3 or 4 patients has been or is currently on a weight-loss injection or is copping to it, since it’s become kind of a trend to have pop-up clinics prescribing injections both online and in real life. Whether it’s Mounjaro or Zepbound, these patients are experiencing gastrointestinal side effects, which range from 14% with diarrhea to 7% with constipation. And this is only the published reports. Anecdotally, I’d say everyone on a GLP-1 agonist is affected in some way. Not necessarily to the point where they’d give up the injection, although a few of my patients have. For the rest, the GI effects are a mild but noticeable annoyance. Do GLP-1 agonists work for weight loss? By all accounts, they do. Patients lose up to 15% of their body weight, when combining GLP-1 agonists with lifestyle modifications. There are also plenty of reports saying that, since GLP-1 agonists combat metabolic syndrome, they’re good for everything from Alzheimer’s to cancer (we will see). In the meantime, here is a list of common GLP-1 agonists, the rates of GI side effects, and what to do about it!
Glucagon-like peptide-1 (GLP-1) receptor agonists—including semaglutide, liraglutide, dulaglutide, and others—are widely used for the treatment of type 2 diabetes and obesity due to their glycemic control and weight loss benefits. Gastrointestinal adverse events occur in 30–50% of patients using GLP-1 receptor agonists. While nausea and diarrhea are most common, constipation affects 4–24% of users depending on the specific agent and dose. In the largest trial to date, called STEP 1, constipation affected 19% of GLP-1 users.
Semaglutide (Ozempic, Wegovy, Rybelsus): Studies show constipation is reported in approximately 10–20% of users.
Liraglutide (Saxenda, Victoza): Constipation incidence is lower but still present in about 5–15% of cases.
Tirzepatide (Mounjaro): 7% of users have constipation
Dulaglutide (Trulicity): Moderate rates of constipation have been observed, similar to liraglutide.
Exenatide (Bydureon, Byetta): Less commonly associated with constipation but can still occur.
GLP-1 agonists act by delaying gastric emptying via activation of GLP-1 receptors, reducing small bowel motility, decreasing appetite, and, most importantly, altering the gut microbiome and hormone signaling.
All of these mechanisms contribute to variable effects such as increased bowel transit time, decreased gut motility, and altered fluid absorption– to put it simply, your body doesn’t know what to do with food (if you even feel like eating); while some patients experience diarrhea, others develop significant constipation.
Prevention and Management of Constipation
Strategies to prevent or manage GLP-1–associated constipation include:
Dietary fiber intake of 25–35 g/day and adequate hydration (2- 3L of water) to soften stools and stimulate peristalsis.
Use of osmotic laxatives (e.g., polyethylene glycol) or bulk-forming agents (e.g., psyllium) as needed.
Increasing GLP-1 agonist doses slowly to reduce GI side effects.
Assessing for secondary causes of constipation (very common: reduced food intake) in patients on long-term therapy.
In Constipation Nation, Dr. Carmen Fong notes:
“GLP-1 medications are game-changers for weight loss and diabetes—but they slow the gut down in the process. Patients need proactive support to manage constipation, not just reactive treatment.”
Clinical Considerations
Constipation may be underreported, especially in weight-loss settings where GI side effects are expected.
Long-term effects on colonic motility and microbiome remain under investigation.
A tailored approach to bowel regimens and considering the effects of GLP-1 drugs, especially in older adults or those with baseline motility disorders, is essential.
So, this month was Pride Month– June always comes and goes incredibly fast, and then half the year is over! We worked on a Safe Anal Douching guide, with companion video discussion (teaser here), with Cheeky Charity and Polari Labs. Polari has also developed an amazing product called A-Ball, which will revolutionize anal sex (and has a ton of clinical applications I’m excited about).
I have this Perfect Stool Podcast interview here.
And if you sign up for the email list on my website, you get a copy of the same Constipation Prevention guide that I give to my patients, for free!
More news soon– Bummed launch in the fall, a finalist poem for the Society of Asian American Surgeons newsletter, and a vodcast coming soon.
Until next time, that’s just the way the anus wrinkles!