Mounjaro vs Wegovy: What the SURMOUNT-5 Trial Found

SURMOUNT-5 is the first large trial to compare tirzepatide (Mounjaro) directly with semaglutide (Wegovy) for weight management. Over 72 weeks, people on tirzepatide lost an average of 20.2% of their body weight, compared with 13.7% on semaglutide (ACC summary of Aronne et al., NEJM 2025). The trial has limits, and the result does not mean one medicine is right for everyone. That decision belongs with your prescribing doctor.

This topic is also in our free guide, The Weight-Loss Medication Guide. Get it emailed to you

How the trial was set up

Participants: 751 adults with obesity, or overweight with a weight-related condition, without diabetes.
Comparison: weekly tirzepatide versus weekly semaglutide, each increased to the highest dose the participant could tolerate within the approved range.
Length: 72 weeks.
Main measure: percentage change in body weight.

Source: Aronne LJ et al., NEJM 2025;393(1):26–36.

What SURMOUNT-5 reported

Weight: an average loss of 20.2% (22.8 kg) with tirzepatide and 13.7% (15.0 kg) with semaglutide.
Waist: an average reduction of 18.4 cm with tirzepatide and 13.0 cm with semaglutide.
Side effects: gastrointestinal effects were the most common in both groups and occurred mostly while the dose was being increased.

Source: ACC journal scan. These are group averages. Individual results vary, and some people in each group lost more than the average while others lost less.

How this compares with the earlier placebo trials

Before SURMOUNT-5, each medicine had been tested against placebo in separate trials. Those results are broadly consistent with the head-to-head findings:

STEP 1 (semaglutide): 1,961 adults over 68 weeks. Average weight change was −14.9% on semaglutide and −2.4% on placebo; 86.4% of people on semaglutide lost at least 5% of their weight (ACC summary of Wilding et al., NEJM 2021).
SURMOUNT-1 (tirzepatide): 2,539 adults over 72 weeks. Average weight change was −15.0%, −19.5% and −20.9% across three dose levels, versus −3.1% on placebo. At the two higher doses, 50% and 57% of participants lost 20% or more, compared with 3% on placebo (HCPLive summary of Jastreboff et al., NEJM 2022).

Comparing numbers across separate trials is unreliable because the people, durations and methods differ. That is why a direct comparison such as SURMOUNT-5 was run.

Limitations of the trial

SURMOUNT-5 is useful evidence, but it answers a narrow question. Points to keep in mind:

Who ran it, and how. The trial was sponsored by Eli Lilly, the manufacturer of tirzepatide, and was open-label, meaning participants and investigators knew which medicine was being given (Patient Care). Neither point invalidates the result, but both are worth knowing.
Weight is one outcome. The trial measured weight and waist change over 72 weeks. Long-term outcomes such as heart attack and stroke were not its question. Semaglutide has separate cardiovascular outcome data from the SELECT trial, which reported a 20% relative reduction in major cardiovascular events in people with established heart disease (ACC summary of Lincoff et al., NEJM 2023).
Who was included. Participants had obesity, or overweight with at least one weight-related condition, and did not have diabetes (Patient Care). People with diabetes or other conditions may respond differently.
Tolerability is individual. Some people tolerate one medicine better than the other, and a larger average loss is of little use if the medicine cannot be continued.
What happens after. Neither medicine was tested here for what happens once it is stopped. Separate withdrawal studies show substantial regain for both; see what happens when you stop.

The Australian context

Both medicines are TGA-registered for chronic weight management in adults, and neither is PBS-subsidised for weight loss (healthdirect). Wegovy also carries a TGA-approved indication for reducing cardiovascular risk in adults with established heart disease (RACGP newsGP), and Mounjaro is also approved for moderate to severe obstructive sleep apnoea in adults with obesity (healthdirect). These differences, your other health conditions and how you tolerate treatment all bear on the choice. This page does not recommend one medicine over the other; that conversation belongs with your prescribing doctor.

Why it matters if you are planning skin surgery

For some people, losses of this size leave loose skin. What matters for surgical planning is not which medicine was used, but whether your weight has stabilised and whether you intend to continue treatment. See weight-loss injections and your skin and when is the right time for skin removal.

Where to next

If your weight has settled and loose skin is now the main issue, book a consultation with Dr Kumar or take the readiness assessment.