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

Ozempic, Mounjaro, Wegovy and Zepbound can all lead to long-term weight loss, but only Wegovy and Zepbound are approved by the FDA for this use. In studies, Zepbound has led to a 21% weight loss in adults using the highest dose, while Wegovy has led to about a 15% weight loss.

In November 2023, Zepbound, the brand name for Eli Lilly's tirzepatide for weight loss, was approved by the FDA. Wegovy and Zepbound are approved by the FDA for chronic weight management, while Mounjaro and Ozempic are both approved for blood glucose (sugar) control in patients with type 2 diabetes.

Both Ozempic and Wegovy are also approved to reduce the risk of cardiovascular death, heart attack and stroke in people with cardiovascular (heart, blood vessel) disease.

Study Overviews

Zepbound (tirzepatide) for chronic weight management (weight reduction and maintenance) was studied in 2 randomized, placebo-controlled, 72-week long, studies (SURMOUNT-1 and SURMOUNT-2) in over 3,400 adults with obesity or excess weight (overweight) and at least one weight-related condition. The primary endpoints of the studies were mean percent change in body weight and the percentage of patients achieving ≥5% weight reduction from baseline to Week 72.

Zepbound: SURMONT-1

• The average starting weight for study participants in SURMOUNT-1 was 105 kg (231 lb). Patients who did not have type 2 diabetes received Zepbound 5 mg, 10 mg or 15 mg injection once weekly, and achieved a statistically significant reduction in body weight compared to those who received placebo.
• At the highest dose (15 mg), people using Zepbound lost an average of 21.8 kg (48 lb) or 21% of their body weight, while at the lowest dose (5 mg), people lost an average of 15.5 kg (34 lb) or 15% of their body weight, compared to 3.2 kg (7 lb), or 3%, on placebo. The percent of patients using Zepbound that lost 5% or more of their body weight ranged from 85% to 91%, based on dose.
• One in three patients taking Zepbound at the highest 15 mg dose lost over 25% of their body weight (26.4 kg / 58 lb) compared to 1.5% in the placebo group (data not controlled for type 1 error).

Zepbound: SURMONT-2

• The average starting weight for adult participants in SURMOUNT-2 was 101 kg (222 lb). All patients had a diagnosis of type 2 diabetes, as well as obesity or overweight.
• Those randomized to receive the highest approved dosage of Zepbound (15 mg once weekly) lost on average 12% of their body weight compared to those randomized to placebo.

Wegovy / Ozempic

Wegovy and Ozempic both contain the active ingredient semaglutide, but are approved for different uses.

• Wegovy (semaglutide), approved for chronic weight management, has resulted in about an average 15% weight loss in adults and a 16.1% decrease in body mass index (BMI) in children 12 years of age and older.
• Ozempic (semaglutide), when used in adults with type 2 diabetes to manage blood glucose (sugar) levels, yields a 6% to 7% weight loss.
• Ozempic and Wegovy are both approved for cardiovascular risk reduction. This means they can reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and type 2 diabetes mellitus (Ozempic) or obesity or overweight (Wegovy). Cardiovascular disease involves the heart and blood vessels.

Although studies evaluating weight loss are available (see below in more detail), it is not possible to fully compare study results for all of these drugs outside of a clinical study as patient populations, doses and study designs differ. There are no studies directly comparing all of these medicines.

What are Ozempic, Mounjaro, Wegovy, and Zepbound approved for?

• Both Mounjaro and Ozempic are approved to help control blood glucose (sugar) levels in patients with type 2 diabetes.
• Ozempic is also approved to reduce the risk of major cardiovascular events (like a stroke or heart attack) in adults with type 2 diabetes mellitus and established cardiovascular disease.
• Wegovy and Zepbound are both approved as an adjunct to diet and exercise for chronic weight management in adults with overweight (BMI ≥27 kg/m2) or obesity (BMI ≥30 kg/m2). In adults, Wegovy is also approved to reduce the risk of cardiovascular death, heart attack and stroke in people with cardiovascular (heart, blood vessel) disease and either obesity or overweight.
• Wegovy is also approved for chronic weight management in pediatric patients aged 12 years and older with an initial BMI at the 95th percentile or greater for age and sex (obesity).

All of these medications are used in addition to a reduced calorie diet and increased physical activity, as recommended by your doctor. Your individual results may vary.

Selected Weight Loss Studies (in more detail)

Tirzepatide (Mounjaro, Zepbound) has been shown to lead to weight loss when used to treat adults with or without type 2 diabetes.

Mounjaro weight loss in patients with type 2 diabetes

In Phase 3 studies in patients with type 2 diabetes, those treated with Mounjaro lost an average of 5.5 kg (12 lb) to 11 kg (25 lb) over 52-weeks. Mounjaro is approved by the FDA for treatment of type 2 diabetes.

• Approval was based on 40 to 52 week studies with over 6,200 participants in the Phase 3 SURPASS program. Active comparators were injectable semaglutide 1 mg, insulin glargine and insulin degludec.
• Efficacy was evaluated for Mounjaro 5 mg, 10 mg and 15 mg used alone (monotherapy) or in combination with commonly prescribed diabetes medications, including metformin, SGLT2 inhibitors, sulfonylureas and insulin glargine.
• Participants achieved average A1C reductions between 1.8% and 2.4%. While not indicated for weight loss, participants treated with Mounjaro lost between 5.5 kg (12 lb) and 11 kg (25 lb) on average.
• Stomach side effects occurred in 37% to 44% of Mounjaro-treated patients (20% on placebo). More patients receiving the 5 mg Mounjaro dose (3%), the 10 mg dose (5.4%), and the 15 mg dose (6.6%) discontinued treatment due to gastrointestinal side effects (like nausea, vomiting, and/or diarrhea) than patients receiving placebo (0.4%).

Zepbound weight loss in patients with obesity or overweight

Without type 2 diabetes

Zepbound, approved for chronic weight loss, was evaluated in the SURMONT-1 and SURMONT-2 clinical studies.

The Phase 3 SURMONT-1 study compared weight loss with tirzepatide (Zepbound) to a placebo (inactive) treatment over a 72-week period. Patients did not have a diagnosis of type 2 diabetes.

• The research included more than 2,500 obese adults or overweight adults with at least one comorbidity (high blood pressure, high cholesterol, obstructive sleep apnea or heart disease).
• Patients taking tirzepatide started at a dose of 2.5 mg once-weekly and then increased the dose by 2.5 mg at four-week intervals to reach their final dose. Final maintenance doses were set at 5 mg, 10 mg, or 15 mg. The dose escalation period was 20 weeks.
• During the study, participants also received counseling on a reduced-calorie diet and exercise as an adjunct treatment.

The study co-endpoints were the percentage change in weight (with the 10 mg and/or 15 mg dose) from the start of the study (baseline) and the percentage of participants with a weight loss of 5% or more at 72 weeks, compared to placebo. At the start of the study, the mean weight of participants was 104.8 kg (230.6 lb) with a mean body mass index (BMI) of 38.

All of the study endpoints were met. Weight loss with all three doses as compared to placebo was statistically significant. At the end of the 72-week study, the mean percent (%) weight loss and average weight loss with tirzepatide (Zepbound) was:

• 15% for the 5 mg dose (about a 16 kg [35 lb] weight loss)
• 19.5% for the 10 mg dose (about a 20 kg [45 lb] weight loss)
• 20.9% for the 15 mg dose (about a 22 kg [48 lb] weight loss)
• 3.1% for placebo (about a 3 kg [7 lb] weight loss)

The percentage of patients with a weight loss of 5% or more was 85% to 91% based on dose, compared to 35% with placebo. In addition, 50% to 57% of patients achieved a weight reduction of 20% or more (with the 10 to 15 mg dose) as compared to 3% in the placebo group.

People in the study were able to maintain the weight reduction for the full 72-week study period. At the highest dose, a decrease in waist circumference of 14.5 centimeters (5.7 inches), when adjusted for placebo, was recorded, as well as improvements in blood glucose, cholesterol levels and blood pressure.

The most common side effects were mild-to-moderate nausea, diarrhea and constipation and occurred primarily during the dose escalation period. Treatment discontinuation due to side effects occurred in up to 6.7% of those receiving Zepbound (primary in the first few months due to stomach side effects) and 3.4 % for the placebo group.

With type 2 diabetes

The Phase 3 SURMONT-2 study compared weight loss with tirzepatide (Zepbound) to a placebo (inactive) treatment over a 72-week period. Patients with obesity or overweight did have a diagnosis of type 2 diabetes with an HbA1c of 7% to 10%.

Patients were randomized to receive Zepbound 10 mg, Zepbound 15 mg, or placebo once weekly. Mean body weight at the start of the study was was 100.7 kg (45.8 kg), and enrolled patients also had comorbidities such as high blood pressure, high lipids levels, obstructive sleep apnea, or heart disease.

Weight loss with both Zepbound doses as compared to placebo was statistically significant. Over the 72-week period the mean percent (%) weight loss with tirzepatide (Zepbound) in patients with type 2 diabetes was:

• 12.8% loss for the 10 mg dose (5.9 kg [12.9 lb])
• 14.7% for the 15 mg dose (6.7 kg [14.8 lb])
• 3.2% for placebo (1.5 kg [3.2 lb])

The percentage of patients with a weight loss of 5% or more was 79% to 83% based on dose, compared to 33% with placebo.

Mounjaro vs Ozempic: Weight loss in patients with type 2 diabetes

• The Phase 3 SURPASS studies evaluated Mounjaro for control of blood glucose (sugar) levels in patients with type 2 diabetes; however, in these studies, patients also lost a significant amount of weight.
• Mounjaro demonstrated significant weight reduction across all three weekly doses (5 mg, 10 mg and 15 mg) compared to Ozempic 1 mg.

Approval was based on 5 clinical trials with over 6,200 patients ranging from 40 to 52 weeks. Mounjaro was compared to injectable semaglutide (Ozempic) 1 mg, insulin glargine (Lantus, Toujeo, others) and insulin degludec (Tresiba). Of note, Ozempic is now approved in a higher 2 mg dose, and results vs. Mounjaro may differ with this higher dose.

Efficacy was evaluated for Mounjaro 5 mg, 10 mg and 15 mg used alone or with other commonly prescribed diabetes medications like metformin, SGLT2 inhibitors, sulfonylureas and insulin glargine. Participants achieved average A1C reductions between 1.8% and 2.4%. Weight loss was a secondary outcome in these studies.

While not indicated for weight loss, participants treated with Mounjaro lost between 5.5 kg (12 lb) to 11 kg (25 lb) on average. Weight changes with the comparator agents ranged from a mean weight gain of 1.8 kg (4 lb) to a mean weight loss of 5.9 kg (13 lb).

Related Questions

• 6 Wegovy side effects you need to be aware of
• Ozempic vs Wegovy: What's the difference between them?
• How long until I lose weight on Wegovy?

Wegovy: STEP Phase 3 weight loss studies

In the STEP Phase 3 studies, weight loss with Wegovy was assessed up to 68 weeks (104 weeks in STEP 5) in approximately 4,500 adults without type 2 diabetes taking Wegovy or an inactive placebo. STEP 2 did include those with type 2 diabetes. Groups also were counseled to follow a reduced-calorie diet and increased physical activity. The STEP 2 study also compared semaglutide 1 mg to semaglutide 2.4 mg for weight loss. Results from the STEP 1 through 5 studies showed that semaglutide is superior at weight reduction when compared with placebo or the weekly semaglutide 1 mg dose.

Patients were classified as either obese (BMI ≥30) or with excess weight (BMI ≥27) with a weight-related medical problem (such as high blood pressure or high cholesterol).

• As one study example, in STEP 1, the average starting weight for both groups was about 105 kg (232 lb). Over the 68-week period, adults in the group taking Wegovy lost significantly more weight than those taking an inactive placebo. With Wegovy, an average of 15.9 kg (35 lb), or about 15% of body weight, was seen. Those taking placebo lost an average of 2.7 kg (6 lb), or roughly 2.5% their body weight.
• In addition, about 84% of people taking Wegovy lost 5% or more of their weight (vs. 31% of people on placebo); 66% lost 10% or more (vs. 12% on placebo), and 48% lost 15% or more (vs. 5% on placebo).
• More patients in the Wegovy group stopped treatment due to gastrointestinal (stomach) side effects (nausea, diarrhea, vomiting, constipation, and stomach pain) compared with those in the placebo group (4.5% vs 0.8%).
• In STEP 2, the 2.4 mg Wegovy dose was found to be significantly more effective than the 1 mg semaglutide dose for weight loss.
• Obese or overweight adults using Wegovy in the 104-week long STEP 5 study were able to lose weight and maintain their weight loss at 2 years compared to an inactive placebo.

Wegovy: Weight Loss in Teens

In the Phase 3a STEP TEENS clinical trial with 201 adolescents, participants received either Wegovy or placebo once weekly for 68 weeks in addition to lifestyle interventions.

• Wegovy was found to be superior to placebo in mean percent change in BMI at week 68 (16.1% decrease vs 0.6% increase), which was the primary endpoint.
• Also, 77% of patients in the Wegovy group had a BMI reduction of at least 5% vs. 20% in the placebo group.
• Adolescents treated with Wegovy had greater incidences of gallbladder problems including gallstones, low blood pressure, rash, and itching (when compared to adults treated with Wegovy).

Common adverse reactions in adolescents included: nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, and hypoglycemia in patients with type 2 diabetes, among other side effects.

What are the doses?

Mounjaro, Ozempic, Wegovy and Zepbound are all given weekly as a subcutaneous (under the skin) injection in the abdomen, thigh or upper arm. Products are available as injector pens and can be used by the patient or a caregiver at home, after instruction. These medicines should not be used together or with other GLP-1 or GIP / GLP-1 receptor agonists.

• Mounjaro (tirzepatide) injection single-use pens or vials are available in 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 and 15 mg doses. The recommended starting dosage is 2.5 mg subcutaneously once weekly, increasing to 5 mg once weekly after 4 weeks. If additional blood sugar control is needed, increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose. The maximum dosage is 15 mg subcutaneously once weekly.
• Ozempic (semaglutide) injection pens deliver 0.25 mg, 0.5 mg, 1 mg, and 2 mg doses. The initial dose is 0.25 mg given subcutaneously once weekly (but is not used as an ongoing maintenance dose). After 4 weeks, the dose is increased to 0.5 mg once weekly. The maximum recommended dose of Ozempic is 2 mg weekly. Pens come as 2 mg, 4 mg and 8 mg per pen.
• Wegovy (semaglutide) injection single-dose pens are available in 0.25 mg, 0.5 mg, 1 mg, 1.7 mg and 2.4 mg doses. Start with 0.25 mg subcutaneously once weekly for 4 weeks. In 4 week intervals, increase the dose until a maintenance dose of 2.4 mg is reached.
• Zepbound (tirzepatide) single-use pens deliver 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 and 15 mg doses. The recommended starting dosage is 2.5 mg subcutaneously once weekly, increasing to 5 mg once weekly after 4 weeks. The recommended maintenance dosages are 5 mg, 10 mg, or 15 mg injected subcutaneously once weekly. The maximum dosage is 15 mg subcutaneously once weekly.

How do these drugs work?

Ozempic and Wegovy both contain semaglutide, a GLP-1 (glucagon-like peptide-1) receptor agonist. Semaglutide binds to GLP-1 receptors and stimulates insulin release from the pancreas when needed. It helps with weight loss by slowing down how fast food travels through your digestive tract (called gastric emptying). This may help you to feel fuller for a longer period of time and reduce how much food you consume. Both products are manufactured by Novo Nordisk.

Mounjaro and Zepbound both contain tirzepatide, a dual-acting GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist. GIP and GLP-1 are both natural incretin hormones. Mounjaro lowers fasting and postprandial (after meals) glucose concentration, decreases food intake, and reduces body weight in patients with type 2 diabetes mellitus. Both products are manufactured by Eli Lilly.

As a group, these medicines are often called "incretin mimetics" because they mimic natural hormones we have in our body, like glucagon-like peptide-1 (GLP-1), which can help you feel fuller.

Selected warnings and side effects

The labeling of these medicines carry a Boxed Warning for possible thyroid tumors, including cancer, which has been seen in animal studies. Do not use Ozempic, Mounjaro, Wegovy or Zepbound if you or anyone in 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). Discuss this further with your healthcare provider.

Gastrointestinal (digestive tract) side effects are the most common side effects reported in at least 5% of patients with these medications. Nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion (dyspepsia), and stomach (abdominal) pain have been reported. In some patients, gastrointestinal (digestive system) side effects can be severe enough to lead to treatment discontinuation.

Review the full product information for a complete outline of all side effects, precautions and warnings.

Do Ozempic, Mounjaro, Wegovy, or Zepbound block the intestine?

After these medicines were approved by the FDA, ileus was reported as a possible side effect and updated in the product labels. An ileus (paralytic ileus) is an intestinal blockage that results in the failure of the intestinal contents to pass through the gut, but it doesn't involve a physical blockage. In paralytic ileus, problems with the muscle or nerves found in the intestine interfere with normal muscle contractions.

• The FDA has received over 8,500 reports of gastrointestinal disorders after use of semaglutide medications (Ozempic, Wegovy), according to safety data they published through June 30, 2023. "Ileus" is specifically mentioned as a reaction in 33 cases, including two deaths, according to CBS news.
• These side effects were reported voluntarily from a population of uncertain size. Because of this, it's not always possible to reliably determine how often this side effect occurs or if the drug caused the side effect.

Anesthesia and incretin mimetics

There have also been concerns about the use of incretin mimetics in patients undergoing general anesthesia. The food left in the stomach increases the risk you might vomit while under anesthesia, leading to aspiration into your lungs. This can increase the risk for pneumonia.

The American Society of Anesthesiologists recommend that people on these types of GLP-1 medicines stop taking it prior to surgery. If you have surgery scheduled, be sure your doctor knows if you take one of these medicines at least one week before surgery

Bottom Line

Wegovy (semaglutide) and Zepbound (tirzepatide) are incretin mimetics approved by the FDA for chronic (long-term) weight loss and maintenance.

Ozempic (semaglutide) and Mounjaro (tirzepatide) are approved to manage blood glucose control in patients with type 2 diabetes, but significant weight loss may also occur with these products.

Ozempic and Wegovy are both approved to reduce the risk of cardiovascular death, heart attack and stroke in people with cardiovascular (heart, blood vessel) disease.

All agents are used in addition to a reduced calorie diet and exercise. They are self-administered by subcutaneous (under the skin) pen injection once weekly.

In studies, patients with or without type 2 diabetes have lost weight with semaglutide (brands: Ozempic, Wegovy). Overall, adult patients have seen about a 15% weight loss with Wegovy and a 6% to 7% weight loss with Ozempic. In children 12 years or age and older, a 16.1% decrease in BMI has been observed with Wegovy.

In studies for patients using Zepbound (tirzepatide), a 21% weight-loss (up to 52 lb) using the highest dose (15 mg) was demonstrated in patients without type 2 diabetes. Zepbound was approved by the FDA for use in weight loss on Nov. 8, 2023.

Gastrointestinal side effects like nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion (dyspepsia), and stomach (abdominal) pain can be significant for some patients using incretin mimetics and may lead to treatment discontinuation. Slowly titrating the dose as recommended by the manufacturer may help to reduce stomach side effects.

Other side effects can include injection site reactions, allergic reactions and hair loss.

This is not all the information you need to know about Mounjaro, Ozempic, Wegovy and Zepbound 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.