Semaglutide & Tirzepatide Side Effects: Complete Guide to Contraindications
This article has been recently updated with the latest information and guidelines.
Table of Contents
What are the common side effects and contraindications for semaglutide and tirzepatide?
Common side effects include nausea (20-44%), diarrhea, constipation, and decreased appetite—most resolve within 4-8 weeks. Contraindications include personal/family history of medullary thyroid carcinoma, MEN2 syndrome, pregnancy, and hypersensitivity to the medication.
Medically Reviewed
Dr. Sarah Mitchell
Board-Certified Obesity Medicine Specialist
Last reviewed: January 25, 2026
Understanding the side effect profile and contraindications of semaglutide and tirzepatide is essential for safe, effective weight loss treatment. This comprehensive guide covers everything from common GI symptoms to serious warnings, helping you make informed decisions with your healthcare provider.
Medical Disclaimer
This information is for educational purposes only. Always consult with a qualified healthcare provider before starting, stopping, or modifying any medication. Individual responses vary, and your provider can assess your specific risk factors.
Common Side Effects Overview
Both semaglutide and tirzepatide belong to the GLP-1 receptor agonist class, sharing similar side effect profiles. The majority of side effects are gastrointestinal in nature and tend to diminish as your body adapts to the medication.
Semaglutide (Ozempic®/Wegovy®)
- Nausea: 34% of patients
- Diarrhea: 30% of patients
- Vomiting: 11% of patients
- Constipation: 24% of patients
- Abdominal pain: 20% of patients
Tirzepatide (Mounjaro®/Zepbound®)
- Nausea: 44% of patients
- Diarrhea: 31% of patients
- Vomiting: 18% of patients
- Constipation: 23% of patients
- Decreased appetite: 25% of patients
Absolute Contraindications
Certain conditions make semaglutide and tirzepatide unsafe. These absolute contraindications require choosing alternative treatments:
Do Not Use If You Have:
- Personal or family history of medullary thyroid carcinoma (MTC)
GLP-1 medications carry a black box warning due to thyroid C-cell tumors observed in animal studies
- Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
This genetic condition increases thyroid cancer risk
- Known hypersensitivity to semaglutide or tirzepatide
Previous allergic reactions to the medication or its components
- Pregnancy or breastfeeding
Discontinue at least 2 months before planned conception
Use With Caution
These conditions don't necessarily prevent use but require careful monitoring and discussion with your healthcare provider:
History of pancreatitis
Increased risk of recurrence; monitor for symptoms
Severe gastrointestinal disease
Gastroparesis, inflammatory bowel disease may worsen
Diabetic retinopathy
Rapid glucose improvement may temporarily worsen
Gallbladder disease
Rapid weight loss increases gallstone risk
Kidney impairment
Start at lower doses; monitor hydration
Concurrent insulin or sulfonylureas
Dose adjustment needed to prevent hypoglycemia
Serious But Rare Complications
While uncommon, these serious side effects require immediate medical attention. Clinical trial data shows these occur in less than 1% of patients:
Acute Pancreatitis (0.3%)
Inflammation of the pancreas requiring immediate care. Symptoms include severe upper abdominal pain radiating to the back, nausea, and vomiting that doesn't improve.
⚠️ Seek emergency care for persistent severe abdominal pain
Gallbladder Problems (0.5-2%)
Rapid weight loss can increase gallstone formation. Symptoms include right-sided upper abdominal pain, especially after eating fatty foods, and potential fever.
⚠️ Report persistent right-sided abdominal pain to your provider
Severe Allergic Reactions (<0.1%)
Rare anaphylactic reactions can occur. Signs include difficulty breathing, severe rash, swelling of face/throat, rapid heartbeat, and dizziness.
⚠️ Call 911 immediately for signs of anaphylaxis
Managing Side Effects Successfully
The good news: most side effects are manageable with proper strategies. Here's how Trimi's approach helps patients succeed:
Evidence-Based Side Effect Management
Gradual increases every 4 weeks allow your body to adapt
Smaller, frequent meals and avoiding fatty/spicy foods reduce GI symptoms by 40%
Drinking 64+ oz water daily prevents dehydration and reduces nausea
Taking medication before bed can minimize daytime nausea
24/7 messaging with Trimi providers for concerns and adjustments
Trimi's Safety-First Approach
At Trimi, patient safety is our top priority. Our board-certified physicians thoroughly evaluate each patient before prescribing, ensuring you're an appropriate candidate for GLP-1 therapy.
Patients continue treatment successfully
Provider access for concerns
Discontinuation due to side effects
Ready to Start Safely?
Get a comprehensive medical evaluation with a board-certified physician who will assess your candidacy and create a personalized treatment plan.
Start Your Free Consultation"The key to successful GLP-1 therapy is proper patient selection, gradual dose titration, and proactive side effect management. With these elements in place, the vast majority of patients can tolerate these medications well while achieving clinically meaningful weight loss."
Clinical Safety Research
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Get Started TodayWritten by Dr. Sarah Mitchell
MD, ABOM - Board-Certified Obesity Medicine Specialist
Our team of healthcare professionals specializes in weight management and metabolic health, providing evidence-based information to help you make informed decisions about your health journey.