Side Effects
Comparing Tirzepatide vs Semaglutide Side Effects and Safety
Weight loss medications can have side effects that impact each person's body differently. For example, semaglutide and tirzepatide can both lead to gastrointestinal issues like nausea, diarrhea, and vomiting. If you are trying to lose weight with these medications, understanding how their side effects differ can help you confidently choose the proper treatment for your weight loss goals. This article will help you compare the side effects, safety profiles, and potential effects on your body and weight loss journey of tirzepatide and semaglutide. Additionally, Does Semaglutide Cause Constipation?
MeAgain's GLP-1 app can help you get started on the right track by providing personalized data and insights to inform your decisions about managing your medication.
Table of Contents
Which is Safer, Semaglutide or Tirzepatide?
The use of medications for weight loss is becoming increasingly common. Doctors sometimes prescribe newer type 2 diabetes drugs to help with weight management. This use is “off-label.” Meaning, doctors prescribe the medicine for a use that’s different from the one the Food and Drug Administration (FDA) has approved for.
Tirzepatide vs. Semaglutide for Weight Loss
Two drugs that doctors prescribe for weight loss are tirzepatide and semaglutide. Both drugs can help your brain feel less hungry, but there are some differences to consider with a doctor’s guidance. Research remains unclear as to which of the two medications is a better option for weight loss.
How Semaglutide Works: Mimicking GLP-1
When you eat, your digestive tract releases the hormone glucagon-like peptide-1 (GLP-1), which prompts your body to create more insulin. This hormone can also send signals to your brain indicating fullness. Semaglutide is a GLP-1 receptor agonist that mimics the hormone, making you feel less hungry. Semaglutide is FDA-approved for the treatment of type 2 diabetes under the brand names Ozempic and Rybelsus. Wegovy is the only semaglutide drug that’s approved for use in weight management. But doctors may prescribe the other brand-name drugs off-label for weight loss.
Dual-Action Hormone Mimic
Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist that mimics the GLP-1 and GIP hormones. GIP can also trigger insulin creation and feelings of fullness. Tirzepatide is sold under the brand name Mounjaro, which is approved for the treatment of type 2 diabetes only. Nevertheless, tirzepatide may be prescribed for weight loss under the brand name Zepbound. Note that semaglutide is available as either an oral tablet or an injection, whereas tirzepatide is available only as an injection.
Which is Better for Weight Loss, Semaglutide or Tirzepatide?
Recent studies have compared the effectiveness of semaglutide and tirzepatide in weight loss. Research studies from 2024, 2023, and 2021 suggest that tirzepatide may lead to greater weight loss compared to semaglutide. But there are some important caveats to these studies.
Dosage Discrepancy and FDA Approval
The doses of semaglutide and tirzepatide given to participants were unequal. Semaglutide and tirzepatide work slightly differently, so researchers chose comparable dose levels. Still, the tirzepatide dose was higher, which may have affected the results. Tirzepatide is FDA-approved for overweight or obese people, with or without type 2 diabetes. Nevertheless, studies suggest that semaglutide may be an effective weight loss treatment for people without diabetes.
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Comparing Tirzepatide vs Semaglutide Side Effects
According to obesity experts, people can react differently to GLP-1s, and how your body responds might depend on the medication itself and various factors, including:
Age
Sex
Diet
Amy Schumer's Experience
In a March video posted to her Instagram, comedian Amy Schumer talked about how she switched from semaglutide to tirzepatide and is now having better results. “I tried Wegovy, and I was like, puking, I couldn’t handle it. I don’t know if they’ve changed the formula, whatever. Mounjaro’s been great,” she said. “I’m having a really good experience with it.”
Previously, on a January episode of Howard Stern’s SiriusXM show, Schumer shared that when she was on Ozempic three years ago, she was left “bedridden” and “vomiting.” So why, in Schumer’s case, did semaglutide cause unmanageable side effects, while tirzepatide didn’t? Here’s what to know about semaglutide and tirzepatide side effects, why the drugs don’t always trigger the same reactions, and how to minimize adverse effects while you’re on a GLP-1 medication:
Shared Mechanisms of Semaglutide and Tirzepatide
Semaglutide and tirzepatide have a lot in common. Both are GLP-1 receptor agonist medications that act on GLP-1 receptors in the brain, pancreas, and gastrointestinal tract, thereby controlling blood sugar levels, slowing stomach emptying, and reducing hunger and food cravings. Tirzepatide and semaglutide also share several side effects:
Nausea
Acid reflux or indigestion
Constipation
Common Side Effects of Weight Loss Medications
A complete loss of appetite (beyond the intended effect) is most common, according to Rekha Kumar, MD, an endocrinologist at Weill Cornell Medicine, who told Health. Beyond these, the labels for Zepbound, Mounjaro, Ozempic, and Wegovy all warn users about potential side effects, including diarrhea, vomiting, and stomach pain. But there are slight variations beyond these side effects, particularly for the weight loss versions of these medications.
Wegovy vs. Zepbound
While Wegovy and Zepbound users are both warned about possible fatigue, belching, and heartburn, Zepbound may also cause injection site reactions, allergic reactions, or hair loss, and Wegovy may cause headache, dizziness, bloating, low blood sugar, stomach flu, gas, and a runny nose or sore throat. Generally, however, these side effects are similar. And for both medications, symptoms tend to improve over time as people become accustomed to them, added Jorge Moreno, MD, an internal medicine and obesity medicine physician at Yale Medicine.
Dose-Dependent Side Effects
Morgan Stewart, PharmD, clinical associate professor of pharmacy practice at the University of Texas at Austin, told Health that these side effects are often dose-dependent. That means, regardless of whether people are taking tirzepatide or semaglutide, side effects are “more likely to happen at higher doses,” she said.
Why Might Your Body React Differently to Various GLP-1s?
Though they’re similar, tirzepatide and semaglutide are formulated differently. While semaglutide is just a GLP-1 agonist, tirzepatide is a dual-action medication, which means it’s both a GLP-1 agonist and a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist.
Tirzepatide's Dual Action for Enhanced Benefits
GIP is a hormone primarily responsible for lowering blood sugar. Tirzepatide, which acts on both GLP-1 and GIP receptors, can further lower blood sugar levels, induce weight loss, and improve lipid profiles. This could be why both Zepbound and Mounjaro have been shown to outperform Wegovy and Ozempic in terms of weight loss benefits, said Stewart. It might also be a potential explanation for why some people tolerate the medications differently. In her practice, Stewart said she's noticed that “tirzepatide sometimes causes more side effects than semaglutide because it works on two hormones instead of one.”
Tirzepatide's Milder Gastrointestinal Profile
Kumar has seen the opposite. She said it’s often easier to space out tirzepatide doses and increase them more gradually over time, so she’s noticed tirzepatide is less likely to cause gastrointestinal issues among her patients as compared to semaglutide. Moreno told Health that he’s treated many people who experienced intense side effects with semaglutide that significantly lessened when they switched to tirzepatide. However, “I’ve had the reverse occur as well, where people tolerate semaglutide better,” he explained.
Individual Variability in Side Effect Tolerance
Anecdotal evidence is all that’s out there; there’s little research putting tirzepatide and semaglutide’s side effects head-to-head on a wide scale. It may be that tolerating tirzepatide or semaglutide simply comes down to each individual—people can have different tolerances to medication types and doses depending on their age, genetics, and sex, Kumar said. Lifestyle may change things, too. Your activity levels, the medications you take, and your diet can affect your risk of experiencing GLP-1 side effects, said Kumar. The same applies to your starting dose. “If the starting dose is too high or increased too quickly, side effects like nausea are more likely,” said Stewart.
Reasons for Reduced Side Effects After Switching
So, if you’re having fewer side effects after switching from Ozempic to Mounjaro, for example, it could be because your body handles the formulation better. Or it could be because your physician started you on a lower dose, or you’re now eating well and exercising more consistently.
How Do Side Effects Compare Between Tirzepatide and Semaglutide?
Side effects are similar between tirzepatide and semaglutide, probably because they work similarly for similar indications. Stomach side effects like nausea, vomiting, and diarrhea are most common for both tirzepatide and semaglutide and can occur in over 50% of all patients. Stomach side effects can be severe in some patients, but are usually transient and decrease over the first few months of treatment. But about 4% to 8% of patients in studies stopped treatment, usually due to stomach side effects like nausea, vomiting, and/or diarrhea.
Managing Initial Gastrointestinal Side Effects
Most reports of nausea, vomiting, and diarrhea occur when doses are being increased at the start of treatment. Slowly increasing the dose, as recommended by your healthcare provider, may help to reduce stomach side effects with tirzepatide or semaglutide. These agents do not usually cause low blood sugar (hypoglycemia) unless they are combined with other medications that may cause hypoglycemia, such as:
Sulfonylureas
Insulin
How Often Do Side Effects Occur?
The frequency of side effects can vary among brand-name products, uses, and studies. Below are examples of side effect rates as reported by the manufacturers:
Zepbound
The most common stomach side effects in people using Zepbound (tirzepatide) for weight loss were:
Nausea: 25% to 28% (vs. 8% placebo)
Diarrhea: 19 to 23% (vs. 8% placebo)
Belching / burping: 4 to 5% (vs. 1% placebo)
Vomiting: 8 to 13% (vs. 2% placebo)
Constipation: 11 to 17% (vs. 5% placebo)
Stomach area pain: 9 to 10% (vs. 5% placebo)
Gastroesophageal reflux disease: 4 to 5% (vs. 2% on placebo)
Heartburn: 9 to 10% (vs. 4% placebo)
Other reported side effects for Zepbound included injection site reactions, tiredness, allergic reactions, and hair loss.
Ozempic
The most common stomach side effects with Ozempic were:
Nausea: 16% to 20% (vs. 6% on placebo)
Diarrhea: 9% (vs. 2% on placebo)
Vomiting: 5% to 9% (vs. 2% on placebo)
Constipation: 3% to 5% (vs. 2% on placebo)
Heartburn (dyspepsia): 3% to 4% (vs. 2% on placebo)
Stomach (abdominal) pain: 6% to 7% (vs. 5% on placebo)
Other reported side effects for Ozempic included:
Hypoglycemia (low blood sugar)
Injection site reactions
Elevated amylase and lipase (pancreas enzymes)
Cholelithiasis (gallstones)
Increases in heart rate
Fatigue
Dysgeusia (altered taste)
Allergic reactions and dizziness
Rybelsus
The most common adverse reactions with Rybelsus included:
Nausea: 11% (7mg), 20% (14 mg)
Abdominal pain: 10% (7 mg), 11% (14 mg)
Diarrhea: 9% (7 mg), 10% (14 mg)
Decreased appetite: 6% (7 mg), 9% (14 mg)
Vomiting: 6% (7 mg), 8% (14 mg)
Constipation: 6% (7 mg), 5% (14 mg)
Comparing Side Effect Frequencies Across Studies
The frequency of side effects associated with tirzepatide and semaglutide cannot be directly compared outside of clinical studies, as patient types, doses, and study designs may vary between studies. Whether you experience a side effect, how often it occurs, and its severity may differ from those reported in these studies.
Note: These are not all the reported side effects, precautions, or warnings for semaglutide or tirzepatide, and rates may vary among products. Speak to your healthcare provider if you have questions about drug side effects.
Serious warnings
The labeling for both tirzepatide and semaglutide carries Boxed Warnings, the FDA’s strongest safety warning, for possible increased risk of thyroid tumors, including cancer, which has been seen in animal studies.
Do not use these products if:
You or your family has a history of medullary thyroid carcinoma (MTC), or If you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Symptoms of thyroid tumors can include a mass in the neck, dysphagia (trouble swallowing, dyspnea (shortness of breath) or persistent hoarseness.
Tell your provider if you have a history of pancreatitis, diabetic retinopathy (vision changes), hypoglycemia (low blood sugar), kidney problems, gallbladder disease, or an allergy to any active ingredients in the tirzepatide or semaglutide product. Both tirzepatide and semaglutide can slow gastric emptying (which is slowed or stopped movement of food through your digestive tract). Tell your healthcare provider if you have a history of gastroparesis (delayed stomach motility).
FDA Warns of Intestinal Blockage Risk
In 2023, the FDA updated the side effects for Ozempic (semaglutide) to emphasize that an ileus, an intestinal blockage, has been reported as a possible side effect. In addition to Ozempic, this warning also applies to Mounjaro and Zepbound (tirzepatide), as well as the other semaglutide products Wegovy and Rybelsus.
Understanding the Risk and Symptoms
The FDA cannot reliably determine how often this side effect occurs or if the drug caused the ileus due to the voluntary nature of the reports. Discuss your risk of this side effect with your doctor. Symptoms of an ileus can include:
Stomach area swelling
Gas, bloating
Stomach area pain or cramping
Odor on the breath
Diarrhea or constipation
Trouble passing gas
Nausea or vomiting
Also, inform your healthcare providers if you are scheduled for any procedures or surgeries that may require anesthesia. While you are taking these medicines, pay close attention to any changes in your mood, behaviors, feelings, or thoughts, and call your healthcare provider right away if you have any changes to your mental health, feelings of depression, or thoughts of suicide.
Impact on Oral Medication Absorption
Semaglutide and tirzepatide may decrease the absorption of other oral medicines due to the delayed gastric-emptying effect. Check with your healthcare provider or pharmacist if you take other oral medications. The manufacturer of tirzepatide (Mounjaro, Zepbound) advises females using birth control pills to switch to a non-oral contraceptive method or add a barrier method of contraception (like a condom) for 4 weeks after you start treatment and for 4 weeks after each dose increase.
Which Should I Use, Tirzepatide or Semaglutide?
In the class of incretin mimetics, factors like risk of severe heart disease or kidney disease, heart disease history (former heart attack or stroke), A1C and weight loss needs, presence of obstructive sleep apnea, costs and insurance coverage, and patient and doctor preference are all important considerations when determining which drug to use.
Personalized Treatment Selection
You and your healthcare provider should consider your individual needs when selecting a treatment for type 2 diabetes or weight loss. What may be the best treatment for others may not be the best for you. You might think about:
Heart risk factors: Semaglutide (Ozempic and Wegovy) has been shown to reduce cardiovascular risks like heart attack, stroke, and heart-related death in patients with established heart disease. Cardiovascular outcomes studies for tirzepatide are still ongoing.
Risk for worsening kidney disease: At this time, Ozempic (semaglutide) is the only GLP-1 type drug approved to reduce the risk of worsening kidney disease and cardiovascular death in patients with type 2 diabetes and chronic kidney disease.
Use for obstructive sleep apnea (OSA) in obesity: In December 2024, the FDA approved Zepbound (tirzepatide) as a treatment for moderate to severe obstructive sleep apnea (OSA) in adults with obesity.
Side effects: Studies have shown tirzepatide may have a greater impact on weight loss and A1C levels, but higher doses of tirzepatide are also linked to more severe stomach side effects like nausea, vomiting, and diarrhea.
Dosage form: Most of these products are available as injections. If you prefer not to use an infusion for the treatment of type 2 diabetes, Rybelsus is an oral form of semaglutide that is taken orally once daily.
Use in children: All semaglutide and tirzepatide products are approved for use in adults. At this time, only Wegovy is approved for weight loss in children 12 years and older.
Affordability: Price and insurance coverage are important considerations. Many insurance companies do not cover the costs of these medications, especially those related to weight loss. Check with your insurance provider before deciding on a treatment with your doctor. More affordable options may be available.
Consult Your Healthcare Provider for Complete Information
This is not all the information you need to know about tirzepatide (Mounjaro, Zepbound) or semaglutide (Ozempic, Wegovy, Rybelsus) for safe and effective use, and it does not replace your doctor’s directions. Review the complete patient medication guide and discuss this information, along with any questions you have, with your doctor or other healthcare provider.
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How to Minimize Semaglutide and Tirzepatide Side Effects
With any GLP-1 medication, side effects are likely. The good news is that these side effects are very manageable and often temporary. With proper guidance and monitoring, many patients find these medications tolerable and effective. Most side effects are gastrointestinal, including:
Nausea
Vomiting
Diarrhea
Constipation
Minimizing Side Effects When Starting GLP-1s
These side effects are widespread when starting a GLP-1 medication or increasing the dose. Regardless of which GLP-1 medication you’re taking, there are a few steps you can take to lessen your chance of developing side effects. For one, start at a low dose and gradually increase it over time, Stewart recommended.
Dietary Adjustments and OTC Relief
Eating smaller meals and limiting consumption of fried foods, desserts, and high-fat meats such as steak can also be incredibly helpful for some people, added Moreno, as these foods can exacerbate adverse gastrointestinal side effects. Prescription or over-the-counter anti-nausea or constipation medications can also be a good way to alleviate some of these issues.
The Importance of Hydration
It’s crucial to stay hydrated, too, Kumar said. People often forget to drink water when their appetite is suppressed. “I have seen such bad dehydration that people land in the [emergency room] with kidney failure,” she said. Suppose you continue to experience harsh or uncomfortable side effects day after day.
When to Consult Your Doctor About Side Effects
In that case, it’s best to talk to your doctor—especially if GLP-1 side effects are interfering with your ability to function. In these situations, Kumar said she usually advises patients to discontinue their GLP-1 to see if the side effects subside. From there, she’ll ask for a detailed account of her patient’s diet to see if certain foods or beverages might have triggered the bad reaction.
Personalized Approach to Obesity Treatment
Depending on those answers, she’ll have the patient try a lower dose of the drug with a few behavioral changes, or she’ll switch their medication. Every person—and body—is unique, said Moreno, and physicians treating obesity should tailor the treatment plan to each patient’s specific needs. “Obesity treatment is not a one-size-fits-all approach,” he said.
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