emaglutide and tirzepatide are two of the most widely used GLP-1–based medications for weight loss and type 2 diabetes management. Both semaglutide and tirzepatide are effective, but they can affect people differently — especially when it comes to side effects. Understanding how these medications compare can help you choose the option that feels safest and most comfortable for your body.
Active Ingredient: Semaglutide
Semaglutide is a GLP-1 receptor agonist only. It mimics the hormone GLP-1, which helps regulate blood sugar and appetite.
| Brand Name | Manufacturer | Route | FDA-Approved Use | FDA Approval Year |
|---|---|---|---|---|
| Ozempic | Novo Nordisk | Injectable (weekly) | Type 2 diabetes; Cardiovascular risk reduction | 2017 |
| Wegovy | Novo Nordisk | Injectable (weekly) | Chronic weight management | 2021 |
| Rybelsus | Novo Nordisk | Oral (daily tablet) | Type 2 diabetes | 2019 |
Active Ingredient: Tirzepatide
Tirzepatide is a dual agonist — it activates GLP-1 receptors and GIP (glucose-dependent insulinotropic polypeptide) receptors. The added GIP activity may enhance weight loss and blood sugar control compared to GLP-1–only drugs.
| Brand Name | Manufacturer | Route | FDA-Approved Use | FDA Approval Year |
|---|---|---|---|---|
| Mounjaro | Eli Lilly | Injectable (weekly) | Type 2 diabetes | 2022 |
| Zepbound | Eli Lilly | Injectable (weekly) | Chronic weight management | 2023 |
If you’re unsure which medication is right for you, Heally makes it easy to meet with a licensed provider who can walk you through your symptoms, side effects, and goals.
Comparing the side effects of semaglutide and tirzepatide
Semaglutide (e.g., Ozempic, Wegovy) and tirzepatide (e.g., Zepbound, Mounjaro) work in similar ways, but tirzepatide has dual action — it activates both GLP-1 and GIP receptors. Because of this, the side effect profiles overlap but are not identical.
Both medications commonly cause:
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Gastrointestinal symptoms (nausea, vomiting, diarrhea)
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Reduced appetite
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Slower digestion
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Fatigue during dose increases
| Side Effect Category | Semaglutide | Tirzepatide |
|---|---|---|
| Common / Frequent | Primarily causes GLP-1–related digestive symptoms such as nausea, vomiting, diarrhea, constipation, abdominal discomfort, bloating, indigestion, gas, belching, fullness, and occasional injection-site redness. | Similar digestive effects as semaglutide (nausea, vomiting, diarrhea, constipation), but some studies note slightly less constipation. Often includes decreased appetite, fatigue, abdominal pain, headache, and mild injection-site itching or redness. |
| Moderate / Less Common | May cause increased heart rate, taste changes, elevated pancreatic enzymes, and gallbladder issues such as gallstones. | May lead to hypoglycemia when combined with other glucose-lowering medications and can cause slightly more injection-site reactions in some patients. |
| Serious / Rare Risks | Includes pancreatitis, gallbladder disease, severe GI events, rare allergic reactions, and a boxed warning for potential thyroid C-cell tumors (based on animal studies). | Shares similar risks—pancreatitis, gallbladder issues, thyroid C-cell tumor warning—while also carrying a risk of kidney problems when dehydration occurs. Long-term safety data is still being gathered due to its newer status. |
However, some users report that tirzepatide feels “smoother” or easier to tolerate, while others find semaglutide gentler. Individual biology plays a major role.
Common side effects of semaglutide
Semaglutide’s most frequently reported side effects include:
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Vomiting
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Diarrhea
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Constipation
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Abdominal discomfort
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Bloating or early fullness
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Fatigue
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Mild headache
These effects usually appear during dose increases and often improve over time.
Common side effects of tirzepatide
Tirzepatide shares many GLP-1–related effects but may also include GIP-related responses:
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Nausea
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Diarrhea
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Decreased appetite
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Constipation
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Indigestion
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Fatigue
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Injection-site discomfort
Some clinical studies suggest tirzepatide may cause slightly less nausea at equivalent effectiveness levels, but this varies from person to person.
Rare but serious side effects: semaglutide vs tirzepatide
Both medications carry similar rare risks, including:
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Pancreatitis
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Gallbladder issues
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Severe gastrointestinal distress
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Low blood sugar (when combined with other diabetes meds)
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Possible thyroid tumor risk (based on animal studies)
Research is ongoing, and these risks remain rare — but they do matter when choosing a long-term treatment.
Which medication has fewer side effects?
There is no universal answer, but trends from studies and patient reports suggest:
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Semaglutide may cause more nausea in some users.
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Tirzepatide may cause more appetite suppression, which some experience as positive and others as uncomfortable.
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Tirzepatide may have slightly higher GI tolerance at certain doses, but not for everyone.
The “better tolerated” medication depends heavily on your digestion, metabolism, and medical history. A consultation is the best way to determine which fits your body.
When should you consider switching from semaglutide to tirzepatide?
A provider may recommend switching if you:
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Experience persistent nausea or GI symptoms on semaglutide
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Hit a weight-loss plateau
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Aren’t achieving desired glucose or appetite control
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Prefer a medication with potentially smoother dose escalation
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Want to explore dual-agonist benefits (GLP-1 + GIP)
Switching should always be done with professional guidance, especially regarding timing and dose adjustments.
Managing side effects of semaglutide and tirzepatide
Helpful strategies include:
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Increasing doses more slowly
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Eating smaller, more frequent meals
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Avoiding high-fat or heavy foods on dose days
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Staying hydrated and prioritizing electrolytes
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Taking the medication at the same time weekly
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Using gentle movement to improve digestion
Most side effects improve once your body adapts.
Booking a consultation through Heally for side effect management
If you’re struggling with side effects — or trying to choose between semaglutide and tirzepatide — a licensed provider on Heally can help you adjust your plan, choose the right medication, and stay on track.
How Heally can help with medication choices and side effect management
Heally connects you with licensed clinicians who can:
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Review your medical history
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Compare semaglutide vs. tirzepatide based on your goals
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Help you manage side effects
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Adjust dosing or recommend switching
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Guide you safely through your weight-loss journey
Heally can connect you with a provider who understands GLP-1 medications like Zepbound — book a free consultation to get personalized guidance today.
Sources
- New England Journal of Medicine: Once-Weekly Semaglutide in Adults with Overweight or Obesity
- Eli Lilly: News Release: Lilly’s tirzepatide shows additional 21.1% weight loss after 12 weeks of intensive lifestyle intervention, for a total mean weight loss of 26.6% from study entry over 84 weeks
- Drugs.com: Comparing Semaglutide vs Tirzepatide
- People: Weight-Loss Drugs Have Sent a Shocking Number of People to the Emergency Room, New Study Claims
- Healthline: How Do Tirzepatide and Semaglutide Compare for Weight Loss?
- FDA Label: OZEMPIC (Semaglutide Injection) Medication Guide
- FDA Label: WEGOVY (Semaglutide Injection) Medication Guide
- FDA Label: RYBELSUS (Oral Semaglutide) Medication Guide
- FDA Label: MOUNJARO (Tirzepatide Injection) Medication Guide
- FDA Label: ZEPBOUND (Tirzepatide Injection) Medication Guide
Important Medical Information and Disclaimers
Medical Disclaimer
This article,“What Medication has Fewer Side Effects, Semaglutide or Tirzepatide?,” is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider regarding any questions you may have about a medical condition, medication, or treatment plan. Never ignore professional medical advice or delay seeking it because of something you have read here.
GLP-1 receptor agonists such as semaglutide (marketed under brand names Ozempic®, Wegovy®, and Rybelsus®) and the dual GIP/GLP-1 agonist tirzepatide (marketed under brand names Mounjaro® and Zepbound®) are FDA-approved prescription medications for specific uses in type 2 diabetes management and, in some cases, chronic weight management. These medications are not over-the-counter supplements and should be used only under the guidance of a licensed healthcare provider.
Compounded Drug Warning
The FDA has not approved compounded drugs and has issued safety alerts about dosing errors, product contamination, and other quality concerns. Compounded drugs are custom formulations made by pharmacies and may vary in quality, safety, and effectiveness, which can increase the risk of side effects or treatment failure. The FDA has warned against using these versions due to issues with incorrect ingredients, poor storage, or improper dosage. Always get medications from a licensed pharmacy with a valid prescription.
Individual Results May Vary
Responses to GLP-1 therapy can vary from person to person. Factors such as diet, physical activity, sleep quality, underlying medical conditions, other medications, and individual metabolism can all influence both side effects and overall results. Clinical trial outcomes may differ from real-world experiences.
Possible Side Effects GLP-1 medications may include:
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Stomach pain or discomfort
- Decreased appetite
- Indigestion or gas
- Redness, itching, or soreness at the injection site
Most side effects are mild to moderate and may improve as your body adjusts to treatment. If you experience severe or persistent symptoms, contact your healthcare provider promptly.
Boxed Warning (Thyroid C-Cell Tumor Risk)
GLP-1 receptor agonists, including semaglutide, carry an FDA boxed warning regarding the potential risk of thyroid C-cell tumors. Do not use if you or a family member has a history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
When to Seek Immediate Medical Attention
Contact your healthcare provider or seek emergency care if you experience:
- Severe abdominal pain that does not go away
- Signs of an allergic reaction (rash, swelling, difficulty breathing)
- Symptoms of pancreatitis (severe abdominal pain, vomiting)
- Symptoms of severe dehydration (dizziness, confusion, rapid heartbeat)
FDA Adverse Event Reporting
