GLP-1 weight loss medications (such as Wegovy, Ozempic, or Zepbound) are flying off the shelves because of their ability to accelerate weight loss– but unwanted side effects can often follow. While constipation is more common than diarrhea on GLP-1 medications, as a gut health dietitian I’ve also been hearing about diarrhea as a side effect and felt called to investigate further.
I’ve done some digging and chatted with two of my dietitian colleagues in the GLP-1 space, who share expert insights and perspectives on GLP-1 diarrhea. Read on for tips on addressing and managing diarrhea as a side effect of a GLP-1 medication, from a holistic nutrition standpoint.
Table of Contents
What exactly are GLP-1’s? (Quick overview)
GLP-1 stands for glucagon-like peptide-1, aka a hormone produced in your gut that helps regulate blood sugar levels and appetite.
GLP-1 agonists are a class of FDA-approved pharmaceuticals that help reduce and regulate blood sugar levels. While they were originally designed for people with type 2 diabetes, GLP-1s are also getting prescribed and taken for Polyendocrine Metabolic Ovarian Syndrome (PMOS) and for facilitating weight loss.
Types of GLP-1 drugs
At this time, the most popular and commonly prescribed GLP-1 agonist medications available on the market include:
- Dulaglutide (aka Trulicity®)
- Exenatide (Byetta®)
- Exenatide extended-release (Bydureon®)
- Liraglutide (Victoza®)
- Lixisenatide (Adlyxin®)
- Orforglipron (Foundayo®)
- Semaglutide injection (Ozempic® or Wegovy®)
- Semaglutide tablets (Rybelsus®)
- Tirzepatide (Mounjaro® or Zepbound®)
How they work
At the molecular level, GLP-1 agonists are derived from a peptide called exendin-4, which comes from the venom of the “Gila monster” (Heloderma suspectum), a reptile native to the southwestern United States. (1, 2) (Something I feel people deserve to know!)
This compound is found to have natural hypoglycemic (blood sugar-lowering) properties, by the following mechanisms (2):
- Upregulating natural insulin secretin in pancreatic β-cells (the cells responsible for making insulin)
- Increasing β-cell proliferation and survival
- Suppressing glucagon secretion
- Delaying gastric emptying
- Suppressing appetite
In your body, GLP-1 agonists work by molecular mimicry: they mimic natural GLP-1 hormones (which are naturally induced by certain probiotic strains in a healthy gut). These hormones help regulate appetite and food intake, so when your body has higher levels, it can become easier to eat less (which can help facilitate weight loss and/or blood sugar regulation, when combined with dietary modification and exercise). (3)
From a gut health perspective, delayed gastric emptying means the food you ate during a meal will sit in your stomach for longer periods of time. “GLP-1 medications slow gastric emptying, meaning food moves more slowly through the stomach and gut,” says Dr. Su-Nui Escobar, DCN, RDN, FAND. “That’s part of how they support fullness and appetite control, but it also explains many of the GI side effects.”
While this particular mechanism does make it more difficult to overeat, it can also potentially be at the expense of your digestive health (especially if you’re predisposed to gut issues).
How Common is Diarrhea on GLP-1s?
What Statistics Show, versus What Experts are Seeing
Diarrhea does show up as a side effect in clinical trials, and studies report about 30% prevalence of diarrhea among people taking GLP-1 medication. (4) However, Ashley Koff, RD shares that she sees new-onset diarrhea in less than 2 out of every 10 people taking these medications.
You may also be more likely to experience diarrhea during the earlier stages of starting the medication, notes Escobar. “It’s also something I tend to see more early on or with dose increases, when the body is still adjusting,” she shares.
Which Medications are Most Likely to Trigger Diarrhea?
The symptoms may also vary to a certain extent depending on the medication. For example, Escobar notes that in her clinical practice, anecdotally, tirzepatide seems to trigger diarrhea less than semaglutide, but that this varies from one person to another.
Koff adds that she has also observed liraglutide and other oral (versus injectable) variations of these drugs seem to have less reported side effects of diarrhea.
“Interestingly, with newer oral GLP-1s like orforglipron, early clinical trials suggest potentially fewer GI side effects overall,” Escobar says– “but it’s still early data and not a completely different pattern, just a possible shift in tolerability.”
Exploring Root Causes: Why do GLP-1 Drugs Cause Diarrhea?
While the exact mechanism isn’t yet known or well-researched, we’ve got some theories.
Dysmotility and SIBO
Delayed gastric emptying (a known mechanism of GLP-1s) is an independent risk factor for small intestinal bacterial overgrowth (SIBO), a gastrointestinal (GI) disorder characterized by microbial overgrowth in the small intestine (which may present with diarrhea, if you’re dealing with hydrogen SIBO or hydrogen sulfide SIBO). This induced state of impaired gastric peristalsis leads to stagnation of food particles and bacteria in the small intestine, which exponentially increases the risk of microbial fermentation and overgrowth in the small intestine. (5)
However, Koff points out– and I agree– that SIBO may be more likely to develop among people who already had pre-existing gut imbalances, such as dysbiosis (an unhealthy, abnormal gut microbiome characterized by suboptimal levels of healthy, probiotic microbes and a subsequent overgrowth of dysbiotic, dysfunction-causing microbes) and suboptimal digestion before starting a GLP-1 medication.
Pre-existing co-morbidities and other medications/supplements
I’ve heard cases in which people experiencing diarrhea while on GLP-1 medication had their gallbladder removed, and/or were already taking other medications (such as Metformin) which are known to alter digestive secretions and the gut microbiome in ways that may increase their risk of diarrhea.
It’s also worth taking a look at other things you’re consuming. “A lot of people unknowingly or intentionally increase magnesium citrate or caffeine and these can increase risk,” Koff highlights.
Injection timing
Koff recommends considering injection timing as it relates to hormonal cycles (for both men and women), as this may play a direct or indirect role in gut peristalsis. She also advises to take a look at your activity level and what you’re consuming around the time of your injection to see if there are any underlying patterns.
Possible gut microbiome changes
“I do also think that there is an impact on the microbiome – it can be both favorable and unfavorable,” says Koff. (6) However, more research is needed to determine how GLP-1 agonists may potentially alter the gut microbiome.
Other Common GI Side Effects of GLP-1s
In addition to diarrhea and appetite suppression, Escobar and Koff explain that the delayed gastric emptying effects of GLP-1 medications may trigger or exacerbate other GI-related side effects such as:
- Constipation
- Bloating
- Gas
- Burping (especially “sulfur burps,” says Escobar)
- Nausea
- Acid reflux
- Abdominal pain
On a positive note, Escobar points out that GI symptoms often seem to subside for many people, after the first few months. “These symptoms are usually most noticeable the day or the day or two following the injection, and again when the dose is increased,” she explains. “So overall, it’s really the gut adjusting to a new pace of digestion, rather than a constant or persistent effect for most people.”
Why Address GLP-1 Diarrhea Sooner Rather Than Later?
Nutritional status
That being said, if you’re having diarrhea, your body is more likely to be mal-absorbing nutrients, increasing your risk of nutrient deficiencies.
Contrary to the popular narrative “you are what you eat,”, it may be more accurate to say “we are what we digest and absorb,” because the nutrients from food must pass through our gut into our bloodstream before our body can utilize them. 😉
Mental health
There’s a strong gut-brain connection, so if your digestive system and nutritional status are becoming compromised, so will your mental health and cognition (if left unchecked).
Increased SIBO risk
Call me biased, but if there’s any chance you’ve developed new-onset SIBO secondary to starting a GLP-1 medication, the risks might outweigh any potential benefits.
Once SIBO is in your system, if left untreated for too long, it can wear away at the brush border of your small intestine (the site in your gut where certain digestive enzymes get produced and secreted), which may subsequently lead to food intolerances such as lactose intolerance, sucrose (sugar) intolerance, starch intolerance, and/or FODMAP intolerances.
It’s also very difficult to treat SIBO in such a way that it doesn’t come back; one study showed about 43% recurrence within nine months. (7)
Recommended reading: Anatomy of a Holistic & Natural SIBO Treatment Plan
Other side effects
Koff points out that people noticing diarrhea on GLP-1s may want to look out for the following non-GI side effects, which include (but aren’t limited to):
- Hair thinning
- Muscle and bone loss
- Reduced energy and fatigue
- Skin issues
- Dehydration
“Absorbing nutrients is key for bone, muscle, blood sugar etc. and so if you are losing nutrients via loose stool it is a factor,” she explains.
Tips for Managing GLP-1 Diarrhea
- Eat Balanced: “For people experiencing diarrhea on a GLP-1, I usually start with simple nutrition and lifestyle adjustments,” Escobar shares. For some people, this may mean going lighter on heavy fats and added sugars at meal times.
- Optimize Meal Timing: When it comes to optimizing motility, meal timing is important! Your gut cleaning wave needs about three to four hours of fasting between meals to sweep any stagnant food or bacterial debris down and out of your small intestine. Try to stick to balanced meals and snacks at structured times, spaced out every three to four hours throughout the day, without any sweetened beverages between meals.
- Chew Your Food: This simple practice is powerful, but often overlooked! Chew your food to applesauce consistency, or about 30 “chews” per bite of food, to help reduce the burden on your digestive system.
- Add Soluble Fiber: Both Escobar and Koff agree that leaning into soluble fiber can be helpful, if symptoms of diarrhea persist. (8)
- Try Prebiotic and Probiotic Foods: Lean into foods naturally abundant in prebiotics and/or probiotics help to feed your gut microbiome, the ecosystem of microbes that support your body’s digestion and natural GLP-1 production.
- Consider Prokinetic Herbs: While this may seem counterintuitive, if you begin noticing new-onset signs and symptoms of SIBO (which may include diarrhea, constant bloating that doesn’t respond to diet/gets worse with fiber, and new adverse food reactions) you may want to consult with your treatment team about trying a prokinetic herb to help sweep any stagnant food or microbial debris down and out of your small intestine.
“Most of the time, these adjustments are enough while the body is still adapting to the medication,” says Escobar.
However, If all of the above interventions still don’t help, consider ruling out SIBO (and if positive, make sure to check out my go-to holistic SIBO treatment plan here).
Final Thoughts
Diarrhea and upset stomach are less common than constipation, but still possible side effects you can experience after starting a GLP-1 medication. Don’t neglect foundational diet and lifestyle practices like balanced, mindful eating, strategic meal spacing, chewing your food thoroughly, and leaning into soluble fiber.
Whether you’re taking GLP-1 medication for blood sugar control or weight loss, it’s important to make sure you’re taking a holistic approach and not neglecting your gut health. Healthy digestion is foundational for long-term success, especially since your gut microbiome is a major player in your body’s natural GLP-1 production.
Keep in mind, diarrhea can also result from co-occurring conditions (like previous gallbladder removal, excess bile acid production, SIBO or gut dysbiosis). When in doubt, work with a practitioner 1-1 for additional support!
About the Featured Experts
Dr. Su-Nui Escobar is a bilingual Registered Dietitian and Doctor of Clinical Nutrition specializing in nutrition care for individuals using GLP-1 medications, with a focus on weight management for women in perimenopause and menopause. She is a national speaker, educator, and author of The GLP-1 Kitchen, and previously served as a spokesperson for the Academy of Nutrition and Dietetics.
Ashley Koff, RD is the USA Today bestselling author of Your Best Shot (HarperOne), founder of The Better Nutrition Program (BNP), and a pioneering voice behind the emerging weight health movement. A practitioner and thought-leader with more than 25 years of experience, Ashley has helped redefine how we approach weight, shifting the conversation from weight loss to weight health, a science-based framework focused on metabolic function, hormonal regulation, and sustainable outcomes. Through her work with patients, clinicians, leading brands and companies, and health organizations, Ashley has developed practical systems that translate complex nutrition science into personalized strategies people can actually implement. A trusted expert featured across major media and a sought-after educator for health professionals, Ashley has been recognized as one of CNN’s Top 100 Health Makers and named “Hollywood’s Leading Dietitian” by InStyle. Through her clinical work, educational programs, and writing, Ashley continues to lead a growing movement toward better, not perfect, nutrition that supports long-term metabolic and weight health.
Next Steps
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