Tirzepatide vs semaglutide: How do they compare?

Both tirzepatide and semaglutide are prescription medicines used with diet and exercise to treat people with type 2 diabetes or to help people lose and maintain weight loss. They are marketed as the brand name products Ozempic, Rybelsus or Wegovy (semaglutide) and Mounjaro or Zepbound (tirzepatide).

What are the approved uses for Mounjaro, Ozempic and Rybelsus?

Mounjaro, Ozempic and Rybelsus are all used with diet and exercise to help control blood sugar (glucose) levels in adults with type 2 diabetes. Ozempic is also approved to reduce the risk of a major cardiovascular event (like a heart attack or stroke) in adults with type 2 diabetes. Mounjaro has not yet received this indication, although studies are underway.

These drugs can help you reach your A1C goal, which can prevent diabetes complications like heart and blood vessel disease, nerve or vision damage, and kidney failure. A1C is a laboratory test that shows how well your blood sugar is controlled over the long term.

Mounjaro and Ozempic are given as a weekly subcutaneous (under the skin) injections in the abdomen, thigh, or upper arm. You, or a caregiver, can learn to give these injections at home. Rybelsus is given as an oral tablet taken once per day.

Mounjaro, Ozempic and Rybelsus have also been shown in studies to help with weight loss in patients with type 2 diabetes, but they are not specifically FDA-approved for this use.

What are the approved uses for Zepbound and Wegovy?

• Wegovy is a weight loss medicine approved to be used in adults and children 12 years and older with obesity, or excess weight and weight-related health problems (like high blood pressure or high cholesterol).
• Wegovy is also approved in adults with heart disease and obesity or overweight to reduce the risk of serious heart problems, like heart attack, stroke or heart-related death.
• Zepbound is also used for weight loss in adults with obesity or who are overweight with weight-related medical problems.
• Both medicines should be combined with a reduced calorie diet and exercise program.

Wegovy and Zepbound are given as a weekly subcutaneous (under the skin) injection and can be given at home after training from a healthcare provider.

How do semaglutide and tirzepatide work?

Semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound) are both in the class of drugs known as incretin mimetics and work similarly but have some differences in mechanism and dosing. Both drugs are FDA approved in various brand names as treatments for type 2 diabetes and long-term weight loss.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist and mimics the natural GLP-1 hormone in our bodies. It binds to the GLP-1 receptor to exert its effect.

Tirzepatide is a dual-acting glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist and binds to both GIP and GLP-1 receptors. Like GLP-1, GIP is also a natural incretin hormone and may increase the action of tirzepatide.

These medicines work by:

• stimulating insulin release from the pancreas when needed to help lower your blood sugar
• decreasing the amount of sugar made by your liver by suppressing glucagon secretion
• slowing the movement of food through your stomach (gastric emptying) which can help you feel fuller for a longer period of time, decrease your appetite and lead to weight loss.

These medicines should not be used together or with any other GLP-1 or GIP receptor agonists.

How are they given?

Mounjaro, Wegovy, Ozempic and Zepbound are given once per week as injections under the skin (subcutaneously) in the stomach area (abdomen), thigh or upper arm. You or a caregiver can learn to give these injections at home using an injector pen.

Rybelsus is an oral option for type 2 diabetes that you can take by mouth once a day, but it has very specific instructions.

• You must take this medicine on an empty stomach when you first wake up with a sip of plain water only (4 ounces or less) to help it be absorbed correctly.
• Take it 30 minutes before your first food, drink (except a sip of water), or other oral medications.
• Swallow the Rybelsus tablet whole (do not crush, split or or chew it). If you take other medicines first thing in the morning, ask your doctor about a schedule change.

With any of these medicines, your doctor will start you with lower doses to help prevent common stomach side effects like nausea, vomiting, diarrhea which are common to drugs in the incretin mimetic class. Other common stomach side effects may include constipation, indigestion, loss of appetite and stomach area (abdominal) pain.

As you get used to the medicine, your healthcare provider will increase your doses to your regular maintenance doses.

Your doctor may have you take these medicines in combination with other treatments for type 2 diabetes, like metformin, SGLT-2 inhibitors, insulin or sulfonylurea treatments.
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Learn More:

• Dosing for tirzepatide (Mounjaro, Zepbound)
• Dosing for semaglutide (Ozempic, Wegovy, Rybelsus)

How do tirzepatide and semaglutide compare in studies?

Overview

• In a comparative study for type 2 diabetes, semaglutide lowered A1C levels by about 1% to 2%, while tirzepatide lowered A1C by 2% to 2.5%.
• Weight loss with semaglutide ranged from 6 to 10 kg (13.2 to 22 lb). With tirzepatide, weight loss ranged from 7 to 13 kg (15.4 to 28.6 lb). Tirzepatide may have a better effect to help lower blood sugar and lead to weight loss in some patients, but may be associated with more stomach side effects at higher doses.
• Semaglutide (Ozempic and Wegovy) have been shown to reduce cardiovascular risks, like heart attack, stroke and heart-related death, in patients with type 2 diabetes or obesity and established heart disease. Both products are FDA-approved for this use. Cardiovascular outcomes studies for tirzepatide are still ongoing.
• One U.S. study, utilizing a cost needed to treat analysis, has shown that tirzepatide (Zepbound) may offer a better value for money when compared to semaglutide (Ozempic) for weight reduction over 68 to 72 weeks.

Semaglutide vs. Tirzepatide: SURPASS-2 study

In the Phase 3, head-to-head study SURPASS-2, tirzepatide (Mounjaro) was compared to semaglutide (Ozempic) in an open-label, 40-week long study with over 1,870 participants with type 2 diabetes. Researchers looked primarily to see how these drugs affected A1C reduction, but also evaluated weight loss.

Mounjaro 5 mg, 10 mg, and 15 mg injections were compared to semaglutide (Ozempic) 1 mg injections in adults with type 2 diabetes whose blood sugars were not controlled with 1,500 mg/day of metformin alone. Patients in the study had an A1C of 8.3% and a weight of 94.1 kg (207 lb) at the beginning of the study.

• Mounjaro reduced the A1C by 2% to 2.3% compared to a 1.9% reduction for participants in the semaglutide (Ozempic) 1 mg group.
• Mounjaro 5 mg, 10 mg or 15 mg also led to weight loss of 7.7 kg (17 lb) to 11.4 kg (25 lb), on average, compared to 5.9 kg (13 lb) for semaglutide (Ozempic).

It’s important to note that the Ozempic 2 mg dose was approved by the FDA in March 2022 for the treatment of type 2 diabetes, and effectiveness compared to Mounjaro with this higher Ozempic dose may have been greater.

In this study, the number of people who reported side effects was similar, but serious side effects occurred more frequently in the tirzepatide group (5.3% to 7%) compared to the semaglutide group (2.8%)

Tirzepatide vs. Semaglutide: Meta-Analysis

A meta-analysis is a type of statistical study used to combine the results of multiple clinical trials to answer a related research question. In one meta-analysis, investigators evaluated studies to compare the effectiveness and safety of tirzepatide to subcutaneous semaglutide in people with type 2 diabetes.

HbA1c: The meta-analysis contained 22 randomized controlled studies with over 18,000 participants. Researchers found that, compared to a placebo, the highest dose of tirzepatide (15 mg given once weekly) was most effective at reducing HbA1c (mean difference of 2%). This was followed by the tirzepatide 10 mg dose (mean difference of 1.86%) and then semaglutide 2 mg (mean difference of 1.62%).

Weight loss: Tirzepatide doses of 10 mg or 15 mg were more effective than 1 mg or 2 mg doses of semaglutide at lowering body weight. Tirzepatide doses of 5 mg were also more effective than 0.5 or 1 mg doses of semaglutide.

Stomach side effects: All doses of both drugs increased the risk for stomach side effects when compared to an inactive placebo, but the highest dose of tirzepatide (15 mg) showed the highest risk for nausea, vomiting and diarrhea.

Cost analysis: Tirzepatide vs. semaglutide for weight loss

A 2023 study determined the cost needed to treat (CNT) to achieve a 1% reduction in body weight using tirzepatide 15 mg vs. semaglutide 2.4 mg. The authors used weight reductions found in previous randomized controlled studies for both drugs (SURMOUNT-1 and STEP-1 studies, respectively).

CNT was calculated by multiplying drug costs (from a common US drug discount website) by follow-up time and dividing it the average weight reduction percentage for each drug vs. placebo.

• Results showed that tirzepatide led to a weight loss of 17.8% compared to 12.4% for semaglutide.
• The total cost of 72 weeks of tirzepatide treatment was estimated to be about $17,500 compared to $22,800 for 68 weeks of semaglutide.
• Overall, the cost to treat each 1% reduction of body weight was $985 with tirzepatide and $1845 with semaglutide.

Learn More: How do Ozempic, Mounjaro, Wegovy, Zepbound compare for weight loss?

How do side effects compare between tirzepatide and semaglutide?

Side effects are similar between tirzepatide and semaglutide, probably because they work in a similar manner 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.

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 medicines that may cause hypoglycemia like the sulfonylureas or insulin.

Related Questions

• How do Ozempic, Mounjaro, Wegovy, Zepbound compare for weight loss?
• 6 Wegovy side effects you need to be aware of
• Ozempic vs Wegovy: What's the difference between them?

How often do side effects occur?

How often side effects occur can differ among brand name products, uses and studies. Below are examples of side effect rates as reported by the manufacturers.

Zepbound side effects

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.

Learn more: Do Ozempic, Wegovy, Mounjaro & Zepbound cause hair loss?

Ozempic side effects

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, and fatigue, dysgeusia (altered taste), allergic reactions and dizziness.

Rybelsus side effects

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)

How often side effects occur with tirzepatide and semaglutide cannot be compared outside of clinical studies as patient types, doses and study designs may differ between the studies. Whether or not you experience a side effect, how often it occurs and its severity may be different from these studies.

Note: These are not all of the reported side effects, precautions or warnings for semaglutide or tirzepatide and rates will differ among products. Speak to your healthcare provider if you have questions about drug side effects. For more information, see:

• Tirzepatide: Side Effects and Warnings
• Semaglutide: Side Effects and Warnings

Serious warnings

The labeling for both tirzepatide and semaglutide carry Boxed Warnings, the FDA’s strongest safety warning, for possible an 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 (slowed stomach motility).

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 exists for Mounjaro and Zepbound (tirzepatide) and the other semaglutide products Wegovy and Rybelsus.

The FDA cannot reliably determine how often this side effect occurs or if the drug actually caused the ileus due to the voluntary nature of the reports. Speak to your doctor about your risk for this side effect.

Symptoms of an ileus can include:

• stomach area swelling
• gas, bloating
• stomach area pain / cramping
• odor on the breath
• diarrhea or constipation
• trouble passing gas
• nausea / vomiting

Also, tell your healthcare providers if you are scheduled for any procedures or surgeries where you may receive any type of 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.

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 medicines.

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.

Related: Mounjaro vs Ozempic: How do they compare?

Cost comparisons

For many patients, access to these medications is difficult due to high costs and lack of insurance coverage. Generics for these medications are not yet available.

Tirzepatide costs

• Mounjaro 5 mg/0.5 mL subcutaneous injection: $1135 per one month supply
• Zepbound 5 mg/0.5 mL subcutaneous injection: $1125 per month supply

Semaglutide costs

• Ozempic 2 mg/3 mL subcutaneous injection: $1029 per month supply
• Wegovy 2.4 mg/3 mL subcutaneous injection: $1430 per month supply
• Rybelsus 7 mg oral tablet: $1,029 for a one month supply of 30 tablets

If you have insurance, the amount you pay for these medications will depend upon your prescription drug coverage, deductible and copay (determined by the “tier” of the drug).

In some cases, the manufacturer may offer a copay coupon that can help lower your costs if you have commercial insurance. Tirzepatide (Mounjaro, Zepbound) is manufactured by Eli Lilly and semaglutide (Ozempic, Rybelsus, Wegovy) is manufactured by Novo Nordisk. Conact them for more details.

Quoted prices are for cash-paying customers and are not valid with insurance plans. This price guide is based on using the Drugs.com discount card which is accepted at most U.S. pharmacies. Prices are always subject to change.

Learn More: Is Mounjaro covered by insurance or Medicare?

Bottom Line: Which should I use - tirzepatide or semaglutide?

In the class of incretin mimetics, factors like risk of severe heart disease, heart disease history (former heart attack or stroke), A1C and weight loss needs, costs and insurance coverage, and patient preference are all important considerations when determining which drug to use.

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) have 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.

Side effects: Studies have shown tirzepatide may have a greater effect 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 injection for treatment of type 2 diabetes, Rybelsus is an oral form of semaglutide that is taken by mouth 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: Cash costs and insurance coverage are important considerations. Many insurance companies will not cover the costs of these medications, especially for weight loss. Check with your insurance before you decide on a treatment with your healthcare provider. More affordable options may be available.

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 does not take the place of your doctor’s directions. Review the full patient medication guide and discuss this information and any questions you have with your doctor or other health care provider.