GLP-1 receptor agonists (GLP-1 RAs) like semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), and exenatide are effective for type 2 diabetes and weight loss. They work by boosting insulin when blood sugar is high, lowering glucagon, and slowing stomach emptying, helping you feel full and lose weight.
However, they’re not right for everyone. Certain conditions, from thyroid cancer risk to digestive disorders, can make these drugs unsafe. As their off-label use for weight loss grows, it’s important to know who should avoid them.
Clinical guidelines and studies suggest you should avoid or use caution with GLP-1 drugs if you have the conditions below.
1. Medullary thyroid carcinoma, MEN2, and family history
Almost all GLP-1 drugs carry a boxed warning for thyroid C-cell tumors, a rare cancer of the thyroid’s parafollicular (C) cells. In animal studies, semaglutide and liraglutide were found to cause C-cell tumors. The risk to humans remains theoretical as no large clinical trial has been conducted, but caution is warranted.
Because of this, manufacturers advise against using these medications in anyone with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia types 2A or 2B (MEN2). If you have a history of thyroid nodules or radiation, talk to your doctor.
In one report, a 63-year-old woman with type 2 diabetes had been using dulaglutide for roughly two years when she noticed a painless lump in her neck. Ultrasound identified a 2 cm thyroid nodule, and her blood test revealed very high levels of calcitonin, a hormone produced by C cells.
A fine-needle biopsy confirmed medullary thyroid carcinoma. She had no personal or family history of MEN2 or radiation exposure. After stopping dulaglutide and undergoing thyroid surgery, her calcitonin levels fell dramatically.
This single case doesn’t prove GLP-1 drugs cause thyroid cancer, but if you have a history of MTC or related conditions, it’s best to avoid them.
2. Diabetic retinopathy and vision changes
Early worsening of diabetic retinopathy can occur when blood sugar levels improve quickly after being poorly controlled. This was first observed in patients with type 1 diabetes who switched from standard insulin to intensive therapy. In some cases, existing retinopathy advanced rapidly within 3-6 months.
GLP-1 drugs are highly effective at lowering blood glucose, which means patients with pre-existing retinopathy may be at risk of early worsening. The risk is higher if you’ve had diabetes for a long time, have poor blood sugar control, or have uncontrolled high blood pressure.
A large 2025 observational study using the Observational Health Data Sciences and Informatics (OHDSI) network found no increased risk of serious eye complications, like proliferative retinopathy or treatment-requiring diabetic macular edema, when semaglutide was compared with other diabetes drugs.
Still, if you already have diabetic eye disease, you should be monitored closely, especially during the first few months of treatment. If you notice blurry vision, floaters, or sudden vision loss, get medical care right away.
3. Pancreatitis
GLP-1 drugs have been associated with acute pancreatitis. In observational studies, the overall risk is still low, but it appears slightly higher than in people not taking these medications. A 2023 research reported higher rates of pancreatitis among GLP-1 users compared with bupropion-naltrexone.
In one report, a 36-year-old woman without a prescription began injecting semaglutide for weight loss. Five weeks into therapy, she developed sudden epigastric pain, nausea, and vomiting. Her lipase level was markedly elevated, and imaging confirmed pancreatitis. She stopped semaglutide, and her pain and laboratory values returned to normal within a week.
Another case involved a 52-year-old man with obesity and a past episode of alcohol-induced pancreatitis. Three months after starting semaglutide, he presented with severe abdominal pain. Laboratory tests showed high white-blood-cell counts and elevated lipase, and a CT scan revealed necrotizing pancreatitis. He recovered after discontinuing the medication and receiving supportive care.
More recently, an elderly patient (93-year-old man) with multiple chronic illnesses developed epigastric pain, nausea, and vomiting after six months on semaglutide. His lipase level was elevated, and imaging confirmed pancreatitis. After stopping semaglutide, he improved.
Because of this, drug labels recommend avoiding GLP-1 medications if you’ve had pancreatitis before. You should also be cautious if you have risk factors like gallstones, high triglycerides, or rapid weight loss, since these can also trigger pancreatitis.
4. Gallbladder diseases
GLP-1 drugs are now being linked to an increased risk of gallbladder disease, especially at higher doses or with long-term use. This includes gallstones (cholelithiasis) and gallbladder inflammation (cholecystitis).
A large safety analysis using the FDA’s adverse event database (covering 2004 to mid-2024) identified 1,829 reports where GLP-1 drugs were suspected to be linked to gallstones and gallbladder inflammation.
Most cases occurred in people age 45 and older, and were more common in women. On average, symptoms developed about 6 months (182 days) after starting treatment, although this varied depending on the specific drug and patient factors.
In one case report, a 66-year-old woman taking high-dose semaglutide (2.4 mg weekly) stopped her dose before a colonoscopy. The day after the procedure, she developed severe abdominal pain around the belly button along with vomiting. Imaging (CT and ultrasound) showed gallstones and an inflamed gallbladder, consistent with acute cholecystitis. She improved with antibiotics and later had her gallbladder removed.
Her doctors suggested that delayed gallbladder emptying from semaglutide, combined with the stress of bowel preparation, may have contributed to the episode.
If you have obesity or type 2 diabetes, you may already have risk factors like insulin resistance, abnormal cholesterol levels, and metabolic changes that make gallstones more likely.
GLP-1 drugs may add to this risk. They promote weight loss, slow gut movement, and reduce how well the gallbladder contracts. Together, these effects can lead to bile buildup and increase the chance of gallstone formation.
That said, researchers still don’t fully understand exactly how these drugs contribute to gallbladder disease.
5. Gastroparesis and bowel obstruction
Because GLP-1 drugs slow how quickly your stomach empties, some people develop symptoms that resemble gastroparesis (delayed stomach emptying) or even bowel obstruction.
Data suggest this risk may be higher. A JAMA research found that, compared with bupropion-naltrexone, GLP-1 users had about a 4-fold higher risk of bowel obstruction and a 3-fold higher risk of gastroparesis. However, experts caution that these may be influenced by underlying diabetes rather than the drugs alone.
Animal studies also show that high-dose GLP-1 therapy can increase intestinal length, which could contribute to obstruction, but this has not been confirmed in humans. The risk appears to increase with longer use, around 1.6 years.
There are also real-world case reports. In one case, a 59-year-old woman with prior abdominal surgeries developed severe abdominal pain and vomiting after her semaglutide dose was increased. Imaging showed dilated bowel loops (up to 3.7 cm) without a physical blockage, suggesting a functional obstruction. Her symptoms improved with supportive care after stopping the drug.
In another case, a 37-year-old woman took a very high dose of semaglutide (4.8 mg) and developed abdominal pain, vomiting, and diarrhea. Imaging again showed dilated intestines without a blockage, consistent with ileus. She recovered within 48 hours after treatment, including nasogastric decompression.
These reports suggest that higher doses or dose increases may raise your risk of functional bowel obstruction, especially if you’ve had prior abdominal surgery or adhesions.
6. Pregnancy and family planning
GLP-1 drugs are not recommended during pregnancy. Animal studies show fetal harm, and human data are very limited. Patients are advised to stop GLP-1 therapy at least two months before a planned pregnancy, since these long-acting drugs can persist in the body.
Drug labels also advise women of childbearing age to use effective birth control and avoid becoming pregnant on these medications. If pregnancy occurs, you should stop the medication and contact your healthcare provider immediately. During pregnancy, insulin or other agents with established safety may be preferred.
7. Lactation and postpartum
Breastfeeding mothers should also avoid GLP-1 drugs. A clinical review states that GLP-1 drugs are not recommended during lactation because there is little data on their transfer into breast milk and potential effects on the infant. Postpartum women may need alternative therapies until they finish breastfeeding.
8. Chronic kidney disease and acute kidney injury
Some GLP-1 drugs are cleared by the kidneys, particularly exenatide. Exenatide is contraindicated in patients with severe renal impairment (creatinine clearance < 30 mL/min) or end-stage renal disease.
There have also been case reports of acute kidney injury in people taking semaglutide and other GLP-1 drugs, especially if they already have kidney disease. In many cases, side effects like vomiting and dehydration reduced blood flow to the kidneys, leading to a temporary decline in kidney function that improved after stopping the medication.
In one case, a woman in her early 80s with chronic kidney disease saw her kidney function (eGFR) drop from about 30 to 11 mL/min after her semaglutide dose was increased. She developed nausea and vomiting, and a biopsy showed significant kidney damage. Her kidney function did not recover even after stopping the drug.
In another case, a man with stage 3 chronic kidney disease had his eGFR fall from around 30 to 24 mL/min after a dose increase. He had weight loss and reduced appetite, but no GI symptoms, and his kidney function remained impaired after discontinuation.
A third case involved a man in his 30s with no prior kidney disease. About six weeks after starting semaglutide, he developed severe kidney failure. A biopsy showed acute interstitial nephritis, and he required dialysis. After stopping the drug and receiving treatment, his kidney function returned to normal within 10 days.
These cases suggest that dose increases and dehydration may trigger kidney injury, especially if you already have kidney disease.
9. Mood and psychiatric considerations
Some reports have raised concerns about mental health effects with GLP-1 drugs, although a clear cause has not been proven.
A large pharmacovigilance study analyzing over 31,000 adverse-event reports for semaglutide, liraglutide, and tirzepatide found that about 1.18% involved psychiatric events, mostly depression and anxiety. Among those psychiatric cases, 19.6% included suicidal thoughts.
The US FDA is currently reviewing these reports. So far, no direct causal link has been confirmed, but regulators advise close monitoring.
There are also case reports. In one case, a 54-year-old man with no prior mental health history developed fatigue, low mood, poor concentration, and excessive sleepiness about one month after starting semaglutide. His symptoms resolved after stopping the drug.
In another case, a 40-year-old woman with a history of major depression experienced worsening depression and suicidal thoughts two months after adding semaglutide to her insulin. Her symptoms improved after stopping the medication and adjusting her antidepressant treatment.
These cases are rare, but if you have a history of depression or suicidal thoughts, you may want to avoid GLP-1 drugs or discuss safer alternatives with your doctor.
10. Type 1 diabetes and diabetic ketoacidosis
GLP-1 drugs are not FDA-approved for type 1 diabetes.
Recent studies do suggest a possible benefit in selected patients, though. A 2025 open-label observational study of 49 people with type 1 diabetes reported significant reductions in weight, A1C, and basal insulin use after 12 months of GLP-1 agonist therapy.
A much larger 2026 Nature Medicine target-trial emulation using national EHR data from 174,678 patients with type 1 diabetes found lower risks of major cardiovascular events and end-stage kidney disease among GLP-1RA initiators, with no observed increase in hospitalization for diabetic ketoacidosis (DKA) or severe hypoglycemia in that analysis.
Still, that study was observational, and earlier trials with liraglutide had reported more symptomatic hypoglycemia and hyperglycemia with ketosis.
If you have type 1 diabetes, GLP-1 drugs are not standard treatment and should only be considered in select cases under specialist care. If you have active DKA, a recent DKA episode, or cannot safely maintain insulin therapy, GLP-1 drugs are not appropriate because they do not replace insulin and may increase the risk of dangerous ketosis if insulin is reduced too much.
11. Allergic reactions and hypersensitivity
Serious allergic reactions to GLP-1 drugs (rash, swelling, difficulty breathing) are rare but possible. Anyone who has experienced anaphylaxis or angioedema after a GLP-1 injection should not take the drug again. Always tell your healthcare provider about past drug allergies, including reactions to preservatives.
12. Eating disorders and malnutrition
Because GLP-1 drugs reduce appetite, they can worsen eating disorders or lead to excessive weight loss. If you have an eating disorder or a history of disordered eating, these medications may not be appropriate.
Bottom line
GLP-1 drugs can be highly effective for blood sugar control and weight loss, but they’re not right for everyone. If you have certain thyroid cancers, severe GI disease, kidney or gallbladder problems, mental health conditions, or are planning a pregnancy, you should use caution.
Rare but serious side effects, like pancreatitis, bowel obstruction, and mood changes, have been reported. Always share your full medical history with your provider, and never start or stop these medications without medical guidance.
Frequently Asked Questions
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Sources
Vemula, H., Villanueva, F. S., Nguyen, H. D., Mohan, A., & Potluri, S. (2021). Medullary carcinoma of thyroid due to GLP-1 receptor agonist. Journal of the Endocrine Society, 5(Supplement_1), A893. https://doi.org/10.1210/jendso/bvab048.1823
Bain SC, Klufas MA, Ho A, Matthews DR. Worsening of diabetic retinopathy with rapid improvement in systemic glucose control: A review. Diabetes Obes Metab. 2019 Mar;21(3):454-466. doi: 10.1111/dom.13538. Epub 2018 Oct 15. PMID: 30226298; PMCID: PMC6587545.
Cai, C. X., Nishimura, A., Baxter, S., Goetz, K., Hribar, M., Toy, B., Barkmeier, A., Wang, S., Swaminathan, S., Flowers, A., Brown, E., Xu, B., Chen, J., Chen, A., Leng, T., Boland, M., Alshammari, T., Bu, F., Falconer, T., . . . Ryan, P. (2025). Semaglutide and diabetic retinopathy: an OHDSI network study. BMJ Open Diabetes Research & Care, 13(6), e005424. https://doi.org/10.1136/bmjdrc-2025-005424
Sodhi, M., Rezaeianzadeh, R., Kezouh, A., & Etminan, M. (2023). Risk of gastrointestinal adverse events associated with Glucagon-Like peptide-1 receptor agonists for weight loss. JAMA, 330(18), 1795. https://doi.org/10.1001/jama.2023.19574
Hughes, K., Sumaruth, Y. R. K., Mohammed, E., & Bakshsingh, V. S. (2024). Acute pancreatitis likely due to semaglutide. Cureus, 16(9), e69844. https://doi.org/10.7759/cureus.69844
Altaweel, T., Mathew, A., Chalasani, P., Lawrence, L., Hussain, S., & Aldaoud, N. (2024). 7947 Semaglutide induced pancreatitis: a case report. Journal of the Endocrine Society, 8(Supplement_1). https://doi.org/10.1210/jendso/bvae163.1071
Ramesh, H. M., Anighoro, S., Subramani, R., & Fabian, D. (2025). MON-639 A case of acute pancreatitis induced by semaglutide. Journal of the Endocrine Society, 9(Supplement_1). https://doi.org/10.1210/jendso/bvaf149.999
Tao, C., Zhang, Y., Wan, T., Zhao, W., Chen, J., Wang, K., Yang, L., Wang, G., Ding, Q., Shang, J., & Zhou, M. (2025). Glucagon-like peptide-1 receptor agonist-induced cholecystitis and cholelithiasis: a real-world pharmacovigilance analysis using the FAERS database. Frontiers in Pharmacology, 16, 1557691. https://doi.org/10.3389/fphar.2025.1557691
Abdulraheem, A., Shukri, D., Altork, N., Afzal, U., Abu-Rumaileh, M., & Meighani, A. (2025). The role of Glucagon-Like peptide-1 (GLP-1) receptor agonists in acute cholecystitis after a routine colonoscopy: a case report. Cureus, 17(2), e79105. https://doi.org/10.7759/cureus.79105
Ramírez-Mejía, M. M., Ponciano-Rodriguez, G., Eslam, M., & Méndez-Sánchez, N. (2025). GLP-1 receptor agonists and gallbladder disease risk: insights into molecular mechanisms and clinical implications. Therapeutic Advances in Endocrinology and Metabolism, 16, 20420188251406456. https://doi.org/10.1177/20420188251406456
GI Adverse Events with GLP-1 Agonists for Weight Loss: Understanding the Risks – American College of Gastroenterology. (2023, November 15). American College of Gastroenterology. https://gi.org/journals-publications/ebgi/phil_paul_nov2023/
Lu, J., Liu, H., Zhou, Q., Wang, M., & Li, Z. (2023). A potentially serious adverse effect of GLP-1 receptor agonists. Acta Pharmaceutica Sinica B, 13(5), 2291–2293. https://doi.org/10.1016/j.apsb.2023.02.020
Nagib, N., Avila, D., Partyka, J., & Kamyab, A. (2025). Weighing the risks: Small bowel obstruction associated with semaglutide use in the postoperative abdomen. Cureus, 17(7), e88589. https://doi.org/10.7759/cureus.88589
Nikolaeva, A., & Vandeputte, M. (2025). Subocclusive ileus following off-label high-dose semaglutide use. Endocrinology Diabetes and Metabolism Case Reports, 2025(4). https://doi.org/10.1530/edm-25-0081
Zipursky, J. S., Bogler, T., & Maxwell, C. (2024). Glucagon-like peptide-1 receptor agonists during pregnancy and lactation. Canadian Medical Association Journal, 196(43), E1413. https://doi.org/10.1503/cmaj.240768
Borkum, M., Lau, W., Blanco, P., & Farah, M. (2022). Semaglutide-Associated Acute Interstitial nephritis: A case report. Kidney Medicine, 4(12), 100561. https://doi.org/10.1016/j.xkme.2022.100561
Leehey, D. J., Rahman, M. A., Borys, E., Picken, M. M., & Clise, C. E. (2021). Acute kidney injury associated with semaglutide. Kidney Medicine, 3(2), 282–285. https://doi.org/10.1016/j.xkme.2020.10.008
Tobaiqy, M., & Elkout, H. (2024). Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database. International Journal of Clinical Pharmacy, 46(2), 488–495. https://doi.org/10.1007/s11096-023-01694-7
FDA. (2026, January 13). Update on FDA’s ongoing evaluation of reports of suicidal thoughts or actions in patients taking a certain type of medicines approved for type 2 diabetes and obesity. U.S. Food And Drug Administration. https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type
Li, J., Cao, J., Wei, J., & Geng, W. (2023). Case Report: Semaglutide-associated depression: a report of two cases. Frontiers in Psychiatry, 14, 1238353. https://doi.org/10.3389/fpsyt.2023.1238353
Ahrén, B., Hirsch, I. B., Pieber, T. R., Mathieu, C., Gómez-Peralta, F., Hansen, T. K., Philotheou, A., Birch, S., Christiansen, E., Jensen, T. J., Buse, J. B., & Investigators, F. T. a. T. (2016). Efficacy and safety of liraglutide added to capped insulin treatment in subjects with Type 1 diabetes: the ADJUNCT TWO randomized trial. Diabetes Care, 39(10), 1693–1701. https://doi.org/10.2337/dc16-0690
Xu, Y., Malek, N. D., Chang, A. R., Echouffo-Tcheugui, J. B., Selvin, E., Grams, M. E., Fang, M., & Shin, J. (2026). Glucagon-like peptide-1 receptor agonists for major cardiovascular and kidney outcomes in type 1 diabetes. Nature. https://doi.org/10.1038/s41591-026-04274-0
Panjawatanan, P., & Comi, R. J. (2025). GLP-1 agonists in Type 1 diabetes – Indications and use. Obesity Medicine, 54, 100591. https://doi.org/10.1016/j.obmed.2025.100591
Kalra, S., Das, A. K., Sahay, R. K., Baruah, M. P., Tiwaskar, M., Das, S., Chatterjee, S., Saboo, B., Bantwal, G., Bhattacharya, S., Priya, G., Chawla, M., Brar, K., Raza, S. A., Aamir, A. H., Shrestha, D., Somasundaram, N., Katulanda, P., Afsana, F., . . . Sumanatilleke, M. (2019). Consensus recommendations on GLP-1 RA use in the management of Type 2 Diabetes mellitus: South Asian Task Force. Diabetes Therapy, 10(5), 1645–1717. https://doi.org/10.1007/s13300-019-0669-4
