Who Shouldn’t Take GLP-1 or GLP-1/GIP Weight Loss Medications?Semaglutide (Ozempic®, Wegovy®) and Tirzepatide (Mounjaro®, Zepbound®) Safety Explained
- Joshua Silva, MD
- Dec 29, 2025
- 7 min read
GLP-1 receptor agonists such as semaglutide (Ozempic®, Wegovy®) and dual GLP-1/GIP agonists such as tirzepatide (Mounjaro®, Zepbound®) are the most effective approved medical weight loss medications to date. Large, randomized trials published in The New England Journal of Medicine demonstrate substantial weight loss along with improvements in blood sugar, blood pressure, kidney outcomes, and cardiovascular risk.
However, effective does not mean appropriate for everyone.
Like all prescription therapies, GLP-1 and GLP-1/GIP weight loss medications have clear safety boundaries. Some people should not take them at all, others may take them only with caution, and many require close physician supervision.
This physician-written guide explains who should and should not take semaglutide or tirzepatide for weight loss, based on the latest medical guidelines.
Quick Answer
Most people can safely use GLP-1 or GLP-1/GIP medications for weight loss under medical supervision.
However:
✅ A small group should not take these medications at all
⚠️ Some should use them with caution
👨⚕️ Many require doctor-supervised weight loss care
Knowing the difference is essential for safety and long-term success.
Absolute Contraindications to GLP-1 and GLP-1/GIP Weight Loss Medications
These are conditions where semaglutide or tirzepatide should not be used, because potential risks outweigh benefits.
Medullary Thyroid Cancer (MTC) or MEN2
Ozempic®, Wegovy®, Mounjaro®, and Zepbound® all carry an FDA boxed warning for patients with:
A personal or family history of medullary thyroid carcinoma (MTC)
Multiple Endocrine Neoplasia type 2 (MEN2) – a condition that predisposes to MTC
This warning is based on rodent data showing thyroid C-cell tumors after GLP-1 exposure. Human trials have not demonstrated increased MTC risk, but given the rarity and severity of the disease, these medications are contraindicated.
Prior Serious Allergic Reaction to a GLP-1 Medication
Anyone who has experienced:
Anaphylaxis
Angioedema (sudden swelling beneath the skin — often of the lips, face, tongue, or throat)
Severe hypersensitivity reaction
…to semaglutide or tirzepatide should not use these medication.
Pregnancy, Actively Trying to Conceive, or Breastfeeding
GLP-1 receptor agonists (such as semaglutide — Ozempic®, Wegovy®) and dual GLP-1/GIP agonists (such as tirzepatide — Mounjaro®, Zepbound®):
Are not approved for use during pregnancy
Caused fetal harm in animal studies
Remain in the body for weeks due to long half-lives
Have limited and insufficient data regarding safety during breastfeeding
For these reasons:
Treatment should be discontinued at least 2 months before a planned pregnancy
GLP-1 and GLP-1/GIP medications are not recommended while breastfeeding
Relative Contraindications (When Semaglutide or Tirzepatide Require Caution)
These conditions do not automatically preclude treatment, but they warrant careful physician evaluation.
History of Pancreatitis
Large clinical trials and meta-analyses have not shown a consistent increase in pancreatitis risk associated with GLP-1 medications.
However, rapid weight loss is known to increase the risk of gallstone formation, and gallstones are a well-established cause of acute pancreatitis.
For this reason, caution is warranted in individuals with a prior history of pancreatitis, particularly since patients at higher risk were often excluded from the clinical trials and meta-analyses referenced above.
Important distinction:
✅ Direct medication effect causing pancreatitis: Not clearly established
⚠️ Ancillary effects: Rapid weight loss and gallstones — both independent risk factors for pancreatitis
Clinical implications:
✅ May be appropriate for carefully selected patients
✅ Requires education regarding abdominal symptoms and prompt evaluation if they occur
❌ Not appropriate for non-medical or questionnaire-based prescribing models
Severe Gastroparesis or Significant GI Motility Disorders
GLP-1 and GLP-1/GIP medications directly slow gastric emptying and intestinal motility. This helps reduce appetite and improve blood sugar, but in people with existing motility problems it can worsen symptoms.
For patients with:
Severe gastroparesis (the stomach empties too slowly, causing nausea, fullness, bloating, or vomiting)
Chronic or unexplained nausea or vomiting
Known severe constipation, ileus, or prior bowel obstruction related to motility
symptoms may worsen on medications like semaglutide (Ozempic®, Wegovy®) or tirzepatide (Mounjaro®, Zepbound®).
Important points:
✅ Direct effect: Slowed gastric emptying and gut motility are direct pharmacologic effects of GLP-1/GIP medications.
⚠️ Common but usually manageable: Constipation and mild bloating are relatively common and often improve with dose adjustment, hydration, and fiber.
❗ Rare but serious: Ileus or bowel obstruction has been reported in rare cases, usually in people with underlying risk factors or severe motility issues.
Clinical implications:
✅ Mild, stable motility symptoms may tolerate slower titration and close follow-up
❌ Severe gastroparesis, ileus, or high-risk obstruction history is generally avoided or requires specialist input
Active Gallbladder Disease
Clinical trials of GLP-1 and GLP-1/GIP weight-loss medications show modest increases in:
Gallstones
Cholecystitis (gallbladder inflammation)
Why this matters:
⚠️ Direct effect: GLP-1 medications can slow gallbladder emptying, which may contribute to gallstone formation.
⚠️ Ancillary effect: Independent of medication, rapid weight loss — regardless of method — increases gallstone risk.
Clinical implications:
✅ Patients with stable, asymptomatic gallbladder disease may still be candidates for GLP-1-based weight loss therapy.
❌ Active gallbladder inflammation, obstruction, or biliary infection requires caution and medical evaluation before treatment.
Conditions That Require Doctor-Supervised GLP-1 Weight Loss
This group highlights why physician-guided programs are fundamentally safer.
Type 2 Diabetes on Insulin or Sulfonylureas
Semaglutide and tirzepatide do not directly cause hypoglycemia.
They are glucose-dependent, meaning they stimulate insulin release only when blood sugar is elevated and have little to no effect when glucose levels are normal or low.
Generally safe with low hypoglycemia risk when used with:
Metformin
Empagliflozin, dapagliflozin (SGLT2 inhibitors)
Pioglitazone, rosiglitazone (TZDs)
sitagliptin, linagliptin (DPP-4 inhibitors)
acarbose, miglitol (alpha-glucosidase inhibitors)
Higher hypoglycemia risk when used with:
Insulin
Sulfonylureas (glyburide, glipizide, glimepiride)
✅ Dose adjustment of insulin and/or sulfonylureas may be required
✅ Strong reason to avoid unsupervised prescribing, as medication changes should be guided by a clinician to prevent low blood sugar episodes
Chronic Kidney Disease
Contrary to common belief:
GLP-1 and GLP-1/GIP medications are not directly harmful to the kidneys
Semaglutide has demonstrated renal protective benefits in large clinical trials
in patients with type 2 diabetes and chronic kidney disease
When risk does occur:
Nausea, vomiting, or diarrhea can lead to volume depletion and dehydration, which may precipitate acute kidney injury—particularly in those with preexisting kidney disease
Clinical implications:
✅ Kidney injury risk is ancillary, related to dehydration rather than direct medication toxicity
✅ Physician guidance helps prevent volume depletion through dose adjustment, hydration counseling, and timely symptom management
Diabetic Retinopathy
Early trials showed transient worsening of retinopathy in patients with:
Long-standing diabetes
Rapid HbA1c (blood sugar) reductions
This phenomenon:
Is not unique to GLP-1 medications
Has long been observed with aggressive glucose control
✅ Likely related to speed of glucose improvement, not direct retinal toxicity✅ Slower dose escalation reduces risk
Older Adults and Risk of Muscle Loss
GLP-1 and GLP-1/GIP medications reduce appetite, and without appropriate guidance regarding nutrition and resistance training, loss of lean body mass can occur during weight loss.
This effect may be more pronounced in older adults, who are already at increased baseline risk of sarcopenia (loss of muscle mass, strength, or function) independent of weight loss.
Key clarification:
❌ This is not muscle toxicity caused by the medication
✅ Lean mass loss occurs with any rapid or substantial weight loss, regardless of method
Clinical implications:
✅ Lean mass loss is an ancillary effect of caloric deficit, not a direct medication effect
✅ Risk is mitigated with adequate dietary protein and resistance exercise
✅ Physician-guided programs improve outcomes by addressing nutrition, activity, and dosing strategy
Why Medical Weight Loss Supervision Matters
Ozempic®, Wegovy®, Mounjaro®, and Zepbound® are metabolic therapies, not cosmetic drugs.
The difference between:
Sustainable weight loss
Avoidable complications
…is medical oversight, not the medication.
Physician-guided GLP-1 weight loss ensures:
Correct screening for contraindications
Safe dosing and titration
Prevention of dehydration and hypoglycemia
Protection of muscle mass and long-term health
Final Takeaway
✅ Most people can safely use semaglutide or tirzepatide for weight loss
✅ A small group should not
✅ Many can safely benefit under proper physician supervision
If you’ve been told you’re “not a candidate,” the real question may be whether you were evaluated medically — or administratively.
Disclaimer:
This article is for educational purposes only and is not a substitute for medical advice.
About the Author
Dr. Joshua Silva, MD, is a licensed physician and Medical Director of Potere Health MD. After graduating medical school from the University of Hawaii, he completed residency training in Occupational and Environmental Medicine from the University of Utah where he also earned a master's degree in Occupation Health. He now specializes in evidence-based weight management, including GLP-1/GIP therapies (semaglutide & tirzepatide). Dr. Silva provides in-person and virtual care for patients with clinics in Salt Lake City, St. George, and Cedar City, Utah.
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