Mounjaro vs Ozempic for Weight Loss: What the Clinical Trials Show

Mounjaro and Ozempic are widely recognised weight-loss injections. The useful comparison is actually Mounjaro versus Wegovy, because Ozempic is the diabetes brand and the obesity trial used semaglutide doses up to 2.4 mg.

Earlier evidence came from separate trials and indirect comparisons. SURMOUNT-5 has now compared tirzepatide and semaglutide prospectively in the same trial.

What are these two medicines?

Ozempic (semaglutide 1 mg injection) is approved for type 2 diabetes. Wegovy (semaglutide 2.4 mg injection) is the higher-dose version approved for chronic weight management. Patients and clinicians often refer to both collectively as "Ozempic." The weight-loss evidence reviewed here uses the 2.4 mg Wegovy dose throughout.

Mounjaro (tirzepatide) is a newer medicine from Eli Lilly that works differently. Semaglutide targets a single receptor: GLP-1 (glucagon-like peptide-1). Tirzepatide activates two receptors in parallel: GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). Both receptors regulate appetite, gastric emptying, insulin release, and energy balance. The dual mechanism is why tirzepatide is sometimes called a twincretin.

Both medicines are weekly subcutaneous injections requiring dose titration over several months to reach the maintenance dose.

SURMOUNT-5: the direct comparison

SURMOUNT-5 (Aronne LJ et al., New England Journal of Medicine, 2025; n=751) was a phase 3b, open-label randomised trial in adults with obesity but without type 2 diabetes. Participants received the maximum tolerated dose of tirzepatide, 10 mg or 15 mg, or semaglutide, 1.7 mg or 2.4 mg, for 72 weeks.

• Mean weight change was 20.2% with tirzepatide and 13.7% with semaglutide.
• Mean waist reduction was 18.4 cm with tirzepatide and 13.0 cm with semaglutide.
• Gastrointestinal events were the most common side effects in both groups. Most were mild to moderate and occurred during dose escalation.

Tirzepatide was superior for average weight and waist reduction in this studied population. The trial was open-label and funded by Eli Lilly, the manufacturer of tirzepatide. It did not test every dose, every patient group or long-term outcomes after treatment ended.

STEP 1: what Wegovy achieved in its phase 3 trial

The STEP 1 trial (Wilding et al., New England Journal of Medicine, 2021) is the pivotal phase 3 study for semaglutide 2.4 mg in obesity without diabetes. It enrolled 1,961 adults and followed them for 68 weeks, randomised to semaglutide 2.4 mg weekly or placebo, with lifestyle counselling for both groups.

Results at 68 weeks:

• Mean weight loss, semaglutide 2.4 mg: 14.9% of body weight
• Mean weight loss, placebo: 2.4%
• 86.4% of semaglutide participants lost at least 5% of body weight
• 69.1% lost at least 10%
• 50.5% lost at least 15%

Nausea was the most common side effect, affecting 44% of the semaglutide group versus 16% on placebo. Most events were mild to moderate and resolved after the titration phase.

SURMOUNT-1: what Mounjaro achieved in its phase 3 trial

The SURMOUNT-1 trial (Jastreboff et al., New England Journal of Medicine, 2022) is the pivotal phase 3 study for tirzepatide in obesity without diabetes. It enrolled 2,539 adults across three active dose arms (tirzepatide 5 mg, 10 mg, and 15 mg weekly) plus placebo, and followed participants for 72 weeks.

Results at 72 weeks:

• Tirzepatide 15 mg: mean weight loss of 20.9% of body weight
• Tirzepatide 10 mg: mean weight loss of 19.5%
• Tirzepatide 5 mg: mean weight loss of 15.0%
• Placebo: mean weight loss of 3.1%
• 57% of patients on tirzepatide 15 mg lost at least 20% of body weight

Nausea occurred in 24.6% to 33.3% of tirzepatide participants depending on dose, compared with 9.5% on placebo. As in STEP 1, most events were mild to moderate and clustered during dose escalation.

Why the older trials still matter

STEP 1 and SURMOUNT-1 show how each medicine performed against placebo in larger phase 3 programmes. They provide broader context on side effects and response ranges, but their raw percentages should not be compared directly because the populations and trial designs differed. SURMOUNT-5 now provides the better direct comparison.

What happens when you stop either medicine

Both semaglutide and tirzepatide are long-term treatments, not simple short courses. Stopping after successful weight loss often leads to weight regain. This matters more for individual treatment selection than people expect, because the question is not only which medicine produces the fastest initial result. It is also which plan can be sustained safely over time.

The SURMOUNT-4 trial (Aronne et al., JAMA, 2024) randomised patients who had already lost weight on tirzepatide to either continue the medicine or switch to placebo for a further 52 weeks. Patients who continued tirzepatide reached a mean of 25.3% weight loss from their original baseline. Patients who stopped and received placebo regained a substantial portion of the weight they had lost. This pattern closely mirrors what was observed in the equivalent semaglutide maintenance study, where discontinuing Wegovy produced rapid weight regain over 12 months.

Long-term treatment continuity, tolerability, and access are therefore as important as peak efficacy figures when choosing between Mounjaro and Ozempic.

Body composition: what the evidence actually shows

Patients frequently ask whether Mounjaro preserves more muscle mass than Ozempic. This would be clinically important, since lean mass loss during weight reduction affects resting metabolic rate and long-term weight maintenance. The evidence on this point is limited and does not currently support superiority claims for either drug.

A 2025 DXA body composition substudy of SURMOUNT-1 participants (Look et al., Diabetes, Obesity and Metabolism, 2025; n=160) found that approximately 75% of weight lost came from fat mass and approximately 25% from lean mass. Lean mass is not the same as skeletal muscle. It also includes water, glycogen, organs and other non-fat tissue.

No peer-reviewed randomised trial has directly compared body composition outcomes between tirzepatide and semaglutide 2.4 mg under controlled, identical conditions. Claims that Mounjaro is substantially superior to Ozempic at preserving muscle are not supported by current primary trial evidence. Both medicines carry a meaningful risk of lean mass reduction that requires active mitigation through nutrition strategy and progressive resistance training.

Side effects: is one medicine better tolerated?

Both medicines cause gastrointestinal side effects during dose escalation. Nausea, vomiting and diarrhoea are the most common. In SURMOUNT-1, nausea affected 24.6% to 33.3% of tirzepatide participants depending on dose. In STEP 1, nausea affected 44% of semaglutide participants. These figures come from separate patient populations and cannot be compared directly.

SURMOUNT-5 found that gastrointestinal events were the most common adverse events in both groups. Individual tolerance varies considerably. Some patients tolerate one medicine well and experience significant side effects from the other. The appropriate approach is to select based on the full clinical profile, titrate carefully and reassess if tolerability becomes problematic.

Who should consider Mounjaro versus Ozempic?

Tirzepatide produced greater mean weight loss than semaglutide in SURMOUNT-5. That is meaningful direct evidence. It does not guarantee that Mounjaro will produce better results for any specific patient.

Several factors matter more for individual treatment selection than population-level averages:

• Diabetes status: which medication is licensed and, where applicable, reimbursed for your diagnosis
• Cardiovascular history and whether outcome evidence applies to your diagnosis
• Prior response to or tolerance of either medicine, if you have taken one before
• Your baseline BMI and the degree of weight loss that would produce meaningful improvements in your metabolic markers
• Contraindications and risk factors, including relevant thyroid cancer history and a history of pancreatitis
• Practical considerations: medicine availability in Estonia or Finland, cost, and your clinic's experience managing both options

This is a medical decision, not a consumer product comparison. Trial data provides a framework. A physician consultation translates that framework into an individual plan based on your specific profile.

Sources

1. Aronne LJ, Horn DB, le Roux CW, et al. "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity." New England Journal of Medicine. 2025;393(1):26-36. Open-label randomised phase 3b trial, n=751. PMID: 40353578. DOI: 10.1056/NEJMoa2416394. Funded by Eli Lilly.
2. Wilding JPH, Batterham RL, Calanna S, et al. "Once-Weekly Semaglutide in Adults with Overweight or Obesity." New England Journal of Medicine. 2021;384(11):989-1002. PMID 33567185. DOI: 10.1056/NEJMoa2032183.
3. Jastreboff AM, Aronne LJ, Ahmad NN, et al. "Tirzepatide Once Weekly for the Treatment of Obesity." New England Journal of Medicine. 2022;387(3):205-216. PMID 35658024. DOI: 10.1056/NEJMoa2206038.
4. Aronne LJ, Sattar N, Horn DB, et al. "Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial." JAMA. 2024;331(1):38-48. PMID 38078870.
5. Look M, Dunn JP, Kushner RF, et al. "Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight." Diabetes, Obesity and Metabolism. 2025. PMID 39996356. DOI: 10.1111/dom.16275.