They are both prescription medications used in conjunction with diet and physical activity to treat type 2 diabetes and to maintain weight loss. When comparing tirzepatide vs semaglutide side effects, it’s important to note that both medications can cause gastrointestinal issues such as nausea and diarrhea, though the severity may vary between individuals. Semaglutide is marketed under the brand names Mounjaro, Rybelsus, or Wegovy, while tirzepatide is marketed under the brands Ozempic or Rybelsus.
Mounjaro and Rybelsus can be used in conjunction with diet and physical activity to control blood sugar levels (glucose). Ozempic has also been approved to reduce the risks of major cardiovascular events (like a stroke or heart attack) among adults with type-2 diabetes. Mounjaro does not have this indication yet, but studies are in progress.
These drugs will help you achieve your A1C target, which is important to prevent complications of diabetes, such as heart disease, blood vessel damage, vision or nerve damage, and kidney failure. A1C is an important laboratory test that shows how well you have managed your blood sugar over time.
Mounjaro or Ozempic is given in weekly subcutaneous injections (under the surface of the skin) into the upper arm, abdomen, or thigh. These injections can be given at home by you or your caregiver. Rybelsus comes as an oral tablet that is taken once a day.
In studies, Ozempic, Rybelsus, and Mounjaro have all been shown to aid in weight loss for patients with type 2 diabetes, though they are not FDA-approved specifically for this purpose.
Wegovy, a weight-loss medicine, is approved for adults and children aged 12 and older who have obesity or excessive weight, along with weight-related problems (such as high blood pressure and high cholesterol).
Wegovy can also be prescribed to adults with obesity or heart disease who are overweight or obese to reduce their risk of heart attacks, strokes, or death.
Zepbound can also be used to help adults lose weight who have obesity or are overweight and have weight-related medical issues.
Both medications should be used in conjunction with a low-calorie diet and an exercise program.
After training by a healthcare professional, Wegovy or Zepbound can be administered at home as a subcutaneous injection (under the surface of the skin).
Both semaglutide and tirzepatide are in the same class of drugs known as incretin mimics. They work in a similar way, but there are some differences between them in terms of mechanism and dosage. The FDA has approved both drugs under various brand names for the treatment of type 2 diabetes and weight loss.
Semaglutide mimics our natural GLP-1 hormone and is a receptor agonist for glucagon-like peptide-1. Semaglutide binds with the GLP-1 receptor to have its effect.
Tirzepatide binds both GLP-1 and GIP receptors and is a dual-acting insulinotropic polypeptide and glucagon-like peptide-1 (GIP) receptor agonist. GIP, like GLP-1, is a natural incretin and can increase the effect of tirzepatide.
When comparing tirzepatide vs semaglutide side effects, it's important to note that both medications can cause gastrointestinal issues such as nausea, diarrhea, and vomiting. However, the intensity and frequency of these side effects may differ between individuals, making it crucial for patients and healthcare providers to evaluate which medication is better tolerated.
These medications should not be taken together with other GLP-1 or GIP receptor agonists.
Mounjaro (abdomen), Wegovy (thigh), Ozempic (upper arm), and Zepbound (stomach area) are all given as subcutaneous injections once a week. You or your caregiver can administer these injections at home using an injector pen.
Rybelsus, an oral treatment for type 2 diabetics that can be taken once daily by mouth, has specific instructions. This medicine must be taken on an empty stomach right after waking up. You can take it with plain water (4 ounces maximum) to ensure proper absorption.
Do not take it before you eat, drink, or use any oral medication.
Rybelsus tablets should be swallowed whole—do not split, crush, or chew them. Ask your doctor if you should adjust the schedule if you are taking other medications first thing in the morning.
Your doctor will prescribe lower doses of any of these drugs to prevent side effects such as nausea, vomiting, and diarrhea, which are all common with incretin mimetic drugs. Constipation, indigestion, and loss of appetite are also common side effects. When comparing Tirzepatide vs Semaglutide side effects, both medications tend to have similar gastrointestinal reactions, but the severity can vary based on individual tolerance.
Your healthcare provider will gradually increase your dosage to your normal maintenance dose as you become accustomed to the medication.
You may be prescribed these medications in conjunction with other treatments for type 2 diabetes, such as metformin, SGLT-2 inhibitors, insulin, or sulfonylureas.
In the Phase 3 head-to-head SURPASS-2 study, semaglutide was compared with tirzepatide in a 40-week open-label study involving more than 1,870 type 2 diabetic participants. Researchers compared the drugs' effects on A1C, as well as weight loss.
Adults with type 2 diabetes who were not controlled by 1,500 mg/day metformin were given Mounjaro injections of 5 mg, 10 mg, or 15 mg. The study included patients with an A1C value of 8.3% and a starting weight of 94.1 kg (207 lb).
Mounjaro decreased the A1C from 2.3% to 2%, compared to 1.9% for the participants in the semaglutide 1 mg group.
Mounjaro 10 mg, 15 mg, or 5 mg led to a weight loss ranging from 7.7 kg (17 lb) to 11.4 kg (25 lb), compared to semaglutide (5.9 kg, 13 lb).
The FDA approved Ozempic at a dose of 2 mg in March 2022 to treat type 2 diabetes. This higher Ozempic dosage may have provided greater effectiveness than Mounjaro.
When comparing tirzepatide vs semaglutide side effects, the number of participants who reported side effects was similar in this study. However, serious side effects were more common among the tirzepatide group (5.2%) than the semaglutide group (2.8%).
Meta-analyses are statistical studies that combine results from multiple clinical trials to answer a research question. Investigators compared the effectiveness and safety between tirzepatide and subcutaneous semaglutide for people with type 2 diabetes in one meta-analysis.
HbA1c: The meta-analysis included 22 randomized controlled trials with more than 18,000 participants. Researchers found that, compared to placebo, the highest dosage of tirzepatide (15 mg given once weekly) was most effective in reducing HbA1c (mean difference of 2%). The tirzepatide dose of 10 mg was next (mean difference of 1.86%), followed by semaglutide 2 mg (mean difference of 1.62%).
Weight loss: Tirzepatide 10 mg and 15 mg were more effective at reducing body weight than semaglutide 1 mg or 2 mg. Tirzepatide 5 mg was also more effective than semaglutide 0.5 mg or 1 mg.
Tirzepatide vs semaglutide side effects: Both drugs were associated with an increased risk of gastrointestinal side effects when compared to a placebo. However, the highest dose (15 mg) of tirzepatide was more likely to cause nausea, vomiting, and diarrhea.
In a study from 2023, the cost-needed-to treat (CNT), to achieve a reduction of 1% in body weight by using semaglutide 2.5 mg or tirzepatide 15, was determined. The authors used the weight reductions from previous randomized controlled trials for both drugs.
CNT was calculated using the following formula: multiply drug costs (from an American drug discount website) and follow-up times, then divide by the average percentage of weight loss for each drug in comparison to placebo.
The side effects of tirzepatide are similar to those of semaglutide, likely because both drugs work similarly for the same indications. When comparing tirzepatide vs semaglutide side effects, both medications can cause gastrointestinal issues such as nausea, vomiting, and diarrhea, which affect over 50% of patients.
Some patients may experience more severe stomach side effects, but these are typically transient and decrease within the first few weeks of treatment. In studies, 4% to 8% of patients stopped treatment due to side effects such as nausea, vomiting, and/or diarrhea.
Most reports of nausea and vomiting occur when the dose is initially increased. As recommended by your doctor, gradually increasing the dosage can help reduce these side effects.
Neither medication causes low blood glucose (hypoglycemia) unless combined with other medications that can cause it, such as sulfonylureas or insulin.
The frequency of side effects can vary depending on the brand, use and study. Here are some examples of the side effects reported by manufacturers.
Most common side effects of Zepbound (tirzepatide), when used for weight loss, were:
Zepbound has also been reported to cause fatigue, allergic reactions, and hair loss.
Ozempic is associated with the following most common side effects:
Ozempic has also been reported to cause hypoglycemia, or low blood sugar, injection site reactions, increased amylase (pancreatic enzymes), cholelithiasis, (gallstones), heart rate increases, fatigue, dysgeusia, (altered taste), allergy reactions, and dizziness.
Rybelsus is associated with the following adverse reactions:
It is not possible to compare the frequency of side effects with tirzepatide or semaglutide outside of clinical trials, as there may be differences in patient types and doses. Also, study designs and design can vary. You may experience side effects differently than these studies, including how frequently they occur and their severity.
Please note that these are not the only side effects, warnings or precautions reported for semaglutide and tirzepatide. Rates will vary among products. If you have any questions regarding drug side effects, speak to your healthcare provider. See:
Both tirzepatide (thyroid tumors) and semaglutide (cancer) are at risk for thyroid cancer. Animal studies have shown this.
Use these products only if you:
Thyroid tumors may cause a lump in the neck or dysphagia, which is difficulty swallowing.
You should tell your doctor if you've had a history or diabetes, diabetic retinopathy, hypoglycemia, kidney disease, gallbladder problems or allergies to the active ingredients of tirzepatide and semaglutide.
Both semaglutide and tirzepatide can cause a slowed gastric emptying. Inform your healthcare provider of any history of gastroparesis.
The FDA updated its side effects in 2023 to include an ileus (an intestinal blockage) as a potential side effect. This warning is also applicable to Mounjaro, Zepbound (tirzepatide), and the semaglutide products Wegovy or Rybelsus.
Due to the voluntary nature, the FDA is unable to determine how frequently this side effect occurs. It also cannot tell if a drug caused the ileus. Talk to your doctor if you are concerned about this side effect.
Tell your healthcare provider if you have any scheduled procedures or surgery where you might receive anesthesia.
If you notice any changes in mood, behavior, feelings or thoughts, you should contact your healthcare provider immediately. This is especially true if you feel depressed or have thoughts of suicide.
Due to their delayed effect on the stomach, semaglutide and tirezepatide can reduce the absorption rate of other oral medications. If you are taking other oral medications, check with your pharmacist or healthcare provider.
The manufacturer of Tirzepatide (Mounjaro and Zepbound), advises women who use birth control pills to switch over to an alternative method (such as a condom). This should be done for four weeks following the start of treatment, or for four weeks following each dose increase.
Due to high prices and lack of coverage, many patients find it difficult to access these medications. These medications do not have generics yet.
Tirzepatide costs
Semaglutide costs
The amount that you will pay for these drugs depends on your insurance coverage, co-pay and deductible (determined by "tier" of drug).
Some manufacturers offer copay coupons that may help you lower your costs, especially if you are covered by commercial insurance. Eli Lilly manufactures tirzepatide, also known as Zepbound, and Novo Nordisk produces semaglutide, which is sold under the names of Ozempic (Rybelsus), Wegovy (Wegovy), and Mounjaro (Mounjaro). For more information, contact them.
When choosing an incretin mimic, it is important to consider factors such as the risk of severe cardiovascular disease, history of heart disease (heart attack or stroke), weight loss requirements, A1C levels, insurance coverage and costs, and the patient's preference.
When selecting a treatment for type 2 diabetes or weight loss, you and your healthcare provider must consider your personal needs. You may not need the same treatment as others. Consider:
Most of these products come in injection form, though Rybelsus, an oral version of semaglutide, is available for those who prefer not to inject themselves.
The information provided here is not intended to replace the advice of your doctor. You should read the entire patient medication guide. Discuss this information with your doctor and other healthcare providers.
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