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Do GLP-1 Agonists Cause Gallstones?
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Safety8 min readJanuary 15, 2025

Do GLP-1 Agonists Cause Gallstones?

Our investigation into the link between GLP-1 medications like semaglutide and tirzepatide and gallbladder problems. What the research shows and what you should know.

By Med Consumer Watch Team
If you're considering or currently taking a GLP-1 medication like semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound), you may have heard concerns about gallbladder problems. This is a legitimate concern worth understanding. In this article, we investigate what the research actually shows about GLP-1 medications and gallstone risk, who may be most at risk, and what you can do to protect yourself.

The Short Answer

Yes, there is a documented connection between GLP-1 agonists and increased risk of gallbladder problems, including gallstones (cholelithiasis) and gallbladder inflammation (cholecystitis). However, the full picture is more nuanced. The risk appears to be primarily related to rapid weight loss rather than the medications themselves. Any method of losing weight quickly—whether through medication, surgery, or severe calorie restriction—increases gallstone risk.

The FDA requires GLP-1 medication labels to include warnings about potential gallbladder problems. This doesn't mean everyone will experience issues, but awareness is important.

What the Research Shows

Multiple clinical trials and real-world studies have examined this connection: Clinical Trial Data: In the STEP trials for semaglutide, gallbladder-related adverse events occurred in approximately 1.6-2.6% of participants taking semaglutide compared to 0.7-1.2% in placebo groups. For tirzepatide (SURMOUNT trials), cholelithiasis was reported in 1.0-1.7% of participants compared to 0.4% with placebo. A 2022 meta-analysis published in JAMA Internal Medicine found that GLP-1 agonist use was associated with increased risk of gallbladder or biliary diseases (relative risk of about 1.27-1.37). Real-World Evidence: A large population-based study using data from millions of patients found similar patterns, with the risk being dose-dependent—higher doses correlating with higher risk.
  • Risk increases with faster weight loss rates
  • Higher doses may carry higher risk
  • Most gallbladder events are mild to moderate
  • Serious complications requiring surgery are less common

Why Rapid Weight Loss Causes Gallstones

To understand this risk, it helps to know how gallstones form: Your gallbladder stores bile, which helps digest fats. When you lose weight rapidly: 1. Fat breakdown increases: Your body breaks down stored fat for energy, releasing cholesterol into the bile. 2. Bile composition changes: The increased cholesterol can supersaturate the bile, making it more likely to crystallize. 3. Gallbladder emptying decreases: When you eat less fat (common during weight loss), your gallbladder contracts less frequently, allowing bile to sit and concentrate. 4. Stones can form: These conditions create the perfect environment for cholesterol crystals to grow into gallstones. This is why the risk isn't unique to GLP-1 medications—it's seen with any rapid weight loss method, including bariatric surgery (where the risk is actually higher, around 30-40% in the first year post-surgery).

Who Is Most at Risk?

Certain factors may increase your risk of developing gallbladder problems while taking GLP-1 medications:
  • Losing weight very rapidly (more than 1.5 kg/3 lbs per week)
  • Higher starting weight or BMI
  • Female sex (women are 2-3 times more likely to develop gallstones)
  • Age over 40
  • Family history of gallstones
  • Previous history of gallbladder problems
  • Native American or Hispanic ethnicity
  • History of yo-yo dieting or rapid weight cycling
  • Very low-fat diets during weight loss

If you have a history of gallbladder problems, discuss this with your healthcare provider before starting GLP-1 therapy. You may need more frequent monitoring.

Recognizing Gallbladder Symptoms

Being able to recognize gallbladder problems early is important. Symptoms to watch for include: Gallstone symptoms (biliary colic): • Sudden, intense pain in the upper right abdomen • Pain that may radiate to the right shoulder or back • Episodes lasting 30 minutes to several hours • Pain often occurs after eating, especially fatty foods • Nausea and vomiting Cholecystitis (gallbladder inflammation): • Severe, persistent abdominal pain • Fever • Nausea and vomiting • Tenderness when touching the abdomen • Pain that worsens with deep breathing

Seek immediate medical attention if you experience severe abdominal pain, fever, jaundice (yellowing of skin/eyes), or clay-colored stools. These could indicate serious complications.

How to Reduce Your Risk

While you can't eliminate gallstone risk entirely during weight loss, several strategies may help reduce it: Gradual weight loss: • Aim for 0.5-1 kg (1-2 lbs) per week when possible • Work with your provider on dosing that achieves steady, sustainable loss Maintain some fat in your diet: • Don't go extremely low-fat; this reduces gallbladder contractions • Include healthy fats from sources like olive oil, avocados, nuts • Aim for at least 7-10 grams of fat per meal Stay hydrated: • Adequate water intake helps maintain bile flow • Aim for 8+ glasses of water daily Consider fiber intake: • Soluble fiber may help reduce cholesterol in bile • Good sources include oats, beans, apples, and psyllium Regular physical activity: • Exercise promotes gallbladder motility • Even moderate activity like walking can help

Some providers prescribe ursodeoxycholic acid (Urso) for patients at high risk of gallstones during rapid weight loss. Ask your provider if this might be appropriate for you.

Should You Avoid GLP-1 Medications?

The gallstone risk should be weighed against the significant health benefits of GLP-1 medications: Benefits to consider: • Substantial, sustained weight loss (15-25%+ of body weight) • Improved blood sugar control • Reduced cardiovascular risk • Lower blood pressure • Improved sleep apnea • Reduced joint pain • Better mobility and quality of life Risk perspective: • Most people on GLP-1s don't develop gallstones • Many gallstones remain asymptomatic (silent) • Symptomatic cases are usually treatable • The health risks of obesity often exceed gallstone risks The key is informed decision-making with your healthcare provider, considering your personal risk factors and health goals.

What If You Develop Gallbladder Problems?

If you do develop gallbladder symptoms while on a GLP-1 medication: First steps: • Contact your healthcare provider promptly • Don't stop your medication without medical guidance • Keep track of when symptoms occur and what triggers them Diagnostic workup typically includes: • Ultrasound (the primary test for gallstones) • Blood tests to check liver and pancreatic function • Possibly HIDA scan to assess gallbladder function Treatment options: • Observation for small, asymptomatic stones • Medication adjustment (lower dose or slower titration) • Ursodeoxycholic acid to help dissolve stones • Surgery (cholecystectomy) for recurrent or severe symptoms Living without a gallbladder: • Most people function normally after gallbladder removal • You can typically continue GLP-1 therapy post-surgery • Some people experience temporary digestive changes

The Bottom Line

GLP-1 agonists like semaglutide and tirzepatide do carry an increased risk of gallbladder problems, primarily related to the rapid weight loss they produce. However, this risk exists with any method of significant weight loss and should be considered in context. For most people, the substantial health benefits of achieving a healthier weight outweigh the gallstone risk. The key is being aware of the risk, knowing the warning signs, and working with your healthcare provider to minimize your chances of problems. If you have significant risk factors for gallstones—especially a previous history of gallbladder issues—discuss this thoroughly with your provider before starting treatment. With proper monitoring and risk-reduction strategies, most people can safely benefit from GLP-1 therapy. Remember: this article provides general information only. Your individual situation may differ, and you should always consult with a qualified healthcare provider about your specific health needs and concerns.

Sources & References

Medical Disclaimer

This article is for informational purposes only and is not intended as medical advice. Always consult with a qualified healthcare provider before making decisions about your health or medications. Individual experiences may vary.

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