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

Q: How do Mounjaro, Wegovy & Ozempic compare for weight loss?

Mounjaro, Wegovy and Ozempic all lead to significant amounts of weight loss, but only Wegovy is currently approved by the FDA for chronic weight management. Mounjaro and Ozempic are both approved to help control blood glucose (sugar) levels in patients with type 2 diabetes, but weight loss has also been seen in Phase 3 clinical trials.

Official answer

by Drugs.com

Mounjaro, Wegovy and Ozempic can all lead to weight loss, but only Wegovy is currently approved by the FDA for chronic weight management. Mounjaro and Ozempic are both approved to help control blood glucose (sugar) levels in patients with type 2 diabetes, but significant amounts of weight loss have also been seen in clinical trials.

In separate studies:

Mounjaro (tirzepatide) has led to the highest amount of weight loss seen in studies, about 21% to 22.5% at the highest dose, in investigational clinical trials evaluating its use for weight management. These numbers approach what is seen with bariatric (weight loss) surgery, according to some clinicians.

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 a 15% weight loss in adults and a 16.1% decrease in BMI in teens. Ozempic (semaglutide), when used in patients with type 2 diabetes to manage blood glucose (sugar) levels, yields a 6% to 7% weight loss. Ozempic is also approved for cardiovascular risk reduction in adults with type 2 diabetes mellitus and established cardiovascular (heart) disease.

Although studies evaluating weight loss are available (see below), it is not possible to fully compare study results for all 3 of these drugs outside of a clinical study as patient populations, doses and study designs differ. There are no studies directly comparing all three of these medicines.

At this time, Wegovy is the only agent of the three approved specifically for weight loss. Phase 3 studies evaluating tirzepatide (Mounjaro) for use as a weight-loss treatment are ongoing.

In Oct. 2022, the FDA granted tirzepatide fast track designation for the treatment of adults with obesity, or overweight with weight-related medical conditions.

It is expected the FDA will fully review the New Drug Application for Mounjaro for the chronic weight management indication in 2023.

In studies, patients with or without type 2 diabetes have lost weight with semaglutide (brands: Ozempic, Wegovy). With Wegovy, patients have seen about a 15% weight loss, and a 6% to 7% weight loss with Ozempic. In the latest investigational studies for patients using Mounjaro, over a 20% weight-loss using the highest dose (15 mg) was demonstrated in patients without type 2 diabetes.

What are Mounjaro, Wegovy and Ozempic approved for?

Both Mounjaro, from Eli Lilly, and Ozempic, from Novo Nordisk, are currently approved to help control blood glucose (sugar) levels in patients with type 2 diabetes, in addition to diet and exercise.

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, from Novo Nordisk, is approved as an adjunct to diet and exercise for chronic weight management in adults and teens. In adults, it is used for overweight (BMI ≥27 kg/m2) or obese (BMI ≥30 kg/m2) patients. In pediatric patients aged 12 years and older, it is used in those with an initial BMI at the 95th percentile or greater for age and sex (obesity).

Selected Weight Loss Studies

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

Mounjaro weight loss in type 2 diabetes

In Phase 3 studies in patients with type 2 diabetes, those treated with Mounjaro lost an average of between 5.5 kg (12 lbs) to 11 kg (25 lbs) over 52-weeks.

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 lbs) and 11 kg (25 lbs) on average.

Stomach side effects occurred in 37% to 44% of Mounjaro-treated patients (20% placebo). More patients receiving the 5 mg dose (3.0%), the 10 mg dose (5.4%), and the 15 mg dose (6.6%) of Mounjaro discontinued treatment due to gastrointestinal side effects (like nausea, vomiting, and/or diarrhea) than patients receiving placebo (0.4%).

Mounjaro weight loss in obesity or overweight: Investigational Use

Mounjaro is not yet approved for weight loss in patients without type 2 diabetes who are overweight or obese; however, this use is currently being studied. Ei Lilly plans to undertake a rolling submission of these studies to the FDA in 2022 and 2023. The SURMONT-1 study has been completed, and the SURMONT-2 study is ongoing with completion expected by April 2023.

On Oct. 6, 2022, the FDA granted a Fast Track designation for tirzepatide for the treatment of adults with obesity, or overweight with weight-related comorbidities. Fast Track designation is meant to speed development and FDA review of promising medicines used to treat serious conditions and may help to fill an unmet medical need for patients.

The Phase 3 SURMONT-1 study published in July 2022 compared weight loss with tirzepatide (Mounjaro) compared to a placebo (inactive) treatment over a 72-week period. These 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. At the end of the 72-week study, the mean percent (%) weight loss with Mounjaro was:

15% for the 5 mg dose

19.5% for the 10 mg dose

20.9% for the 15 mg dose

3.1% for placebo

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 (at the 10 to 15 mg dose) as compared to 3% in the placebo group.

Weight loss with all three doses as compared to placebo was statistically significant. Over the 72-week period the average weight loss with Mounjaro was: 23.6 kg (52 lb) for the 15 mg dose; 22.3 kg (49 lb) for the 10 mg dose; 15.9 kg (35 lb) for the 5 mg dose and 2.3 kg (5 Ib) for placebo. At the highest dose, a decrease in waist circumference of 14.5 centimeters (5.7 inches), when adjusted for placebo, was recorded.

People in the study were able to maintain the weight reduction for the full 72-week study period. At the highest dose of tirzepatide, improvements in blood glucose, cholesterol levels and blood pressure were also observed.

The most common side effects were mild-to-moderate nausea, diarrhea and constipation and occurred primarily during the dose escalation period. Side effects overall caused treatment discontinuation in up to 7.1% of those receiving Mounjaro and 2.6% for the placebo group.

Patients with pre-diabetes at the start of the SURMONT-1 study will remain in the study for an additional 104 weeks to assess the impact on body weight and progression to type 2 diabetes as compared to placebo.

The ongoing SURMONT-2 study is a similar placebo-controlled study to SURMONT-1 with 938 patients. Results will be submitted as available to the FDA per the rolling submission designation. Study completion is expected in April 2023.

Mounjaro vs Ozempic: Weight loss in patients with in 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 lbs) to 11 kg (25 lbs) 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).

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 lbs). 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 lbs), or about 15% of body weight, was seen. Those taking placebo lost an average of 2.7 kg (6 lbs), 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, Wegovy and Ozempic 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 receptor agonists.

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.

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. 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.

Mounjaro is 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.

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, Wegovy or Mounjaro 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 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.

Does Ozempic, Wegovy or Mounjaro cause ileus?

After these medicines were approved by the FDA, ileus was reported as a possible side effect and posted in the product label for all three medicines.

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.

Bottom Line

Only Wegovy (semaglutide) is approved for weight loss by the FDA at this time. 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. All agents are used in addition to a reduced calorie diet and exercise. They are administered by subcutaneous (under the skin) 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 the latest investigational studies for patients using Mounjaro, a 21% weight-loss (up to 52 lb) using the highest dose (15 mg) was demonstrated in patients without type 2 diabetes. The FDA is expected to review the investigational use for weight loss with Mounjaro in 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.

This is not all the information you need to know about these medicines 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.

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