Mounjaro vs Wegovy: how to think about the choice

The 30-second summary

• In head-to-head data (SURMOUNT-5, 2025), tirzepatide produced about 50% more weight loss than semaglutide over 72 weeks, 20.2% vs 13.7%.
• Side-effect profiles are similar in pattern (mostly GI) but tirzepatide tends to cause more constipation and slightly more nausea on titration.
• Insurance coverage, dosing schedule, and what your body tolerates matter more than the average difference. The "best drug" is the one you will actually keep taking.

What you are actually choosing between

Both medications are weekly injections. Both lower appetite by acting on gut-brain receptors. Both have been studied in tens of thousands of people. Both work.

The difference is the receptor they activate:

• Wegovy / Ozempic (semaglutide) acts on one receptor: GLP-1.
• Mounjaro / Zepbound (tirzepatide) acts on two: GLP-1 and GIP.

The second receptor matters. In the head-to-head SURMOUNT-5 trial published in NEJM in 2025, adults with obesity (and without diabetes) lost an average of 20.2% of starting body weight on tirzepatide versus 13.7% on semaglutide over 72 weeks. Both groups lost meaningful weight. Tirzepatide lost roughly 50% more. (Aronne et al., NEJM 2025.)

The same pattern appears in older indirect comparisons. The SURMOUNT-1 trial of tirzepatide alone reported 20.9% loss at the highest dose over 72 weeks. The STEP 1 trial of semaglutide reported 14.9% over 68 weeks. (Jastreboff et al., NEJM 2022; Wilding et al., NEJM 2021.)

Where the averages stop being useful

The averages tell you what a population does. They do not tell you what your body will do.

In every trial, there is a wide spread. Some women on semaglutide lose 25% of their body weight. Some women on tirzepatide lose 8%. Genetics, baseline insulin sensitivity, adherence to titration, sleep, training and food intake all matter. None of those variables are captured by the average.

The practical implication: do not pick the drug your friend lost the most weight on. Pick the drug your prescriber thinks fits your physiology, that your insurance covers, and that you can tolerate without giving up.

Side effects: similar shape, different details

The dominant side-effect category for both drugs is gastrointestinal: nausea, vomiting, diarrhoea, constipation. The pattern is the same, but the proportions tilt differently.

Tirzepatide tends to produce more:

• Constipation (about 17% in SURMOUNT-1 vs about 8% in STEP 1)
• Slightly higher rates of nausea early in titration

Semaglutide tends to produce more:

• Diarrhoea (about 30% vs about 22%)
• Rarely, hair shedding at month 3–4 (we have a separate article on this)

Both drugs share the same FDA black-box warning for medullary thyroid carcinoma risk based on rodent studies. The human signal is small and still under surveillance. Both carry the same pancreatitis warning, the same gallbladder warning, and the same instruction to stop two months before attempting pregnancy.

What your prescriber is probably thinking about

In an honest conversation with a prescriber, the inputs are usually these:

1. Insurance and cost. In the US, coverage varies wildly. In many plans, semaglutide is covered for diabetes (Ozempic) and weight (Wegovy), and tirzepatide is covered as Zepbound. Out of pocket, both are expensive. The drug that is actually affordable is the one that works.
2. Other conditions. If you have type-2 diabetes, the conversation expands. If you are at risk of pancreatitis or have had gallbladder disease, the calculus shifts.
3. Tolerance history. If you tried semaglutide and had to stop because of severe nausea, tirzepatide is not automatically better, both are GLP-1 agonists. But the GIP component sometimes changes the experience.
4. Time horizon. Tirzepatide is newer. Semaglutide has more years of post-marketing data. For many prescribers and patients, that matters.

The "Ozempic" question

You will see Ozempic and Mounjaro mentioned alongside Wegovy and Zepbound. They are the same molecules, with different brand names and different FDA-approved uses:

• Ozempic = semaglutide for diabetes
• Wegovy = semaglutide for weight management
• Mounjaro = tirzepatide for diabetes
• Zepbound = tirzepatide for weight management

If you do not have diabetes, the appropriate prescriptions are Wegovy or Zepbound. Off-label prescribing of the diabetes versions for weight has been common in the United States, and it is a conversation between you and your prescriber, but the trial data that the weight-loss numbers above come from is the weight-indication brand.

How to talk to your prescriber about the choice

A short list, in order of usefulness:

1. What does my insurance cover? Often this answers the question.
2. Have you started other women like me on both? What did you see?
3. What dose level would we be aiming for, and over how long?
4. If we start on one and tolerance is a problem, how easy is the switch?

The answer to the last question is "fairly easy." Switching between GLP-1s is well within standard practice. The drug you start with is not a marriage. It is a starting point.

And the field is still moving: a third option, the triple agonist retatrutide, has posted even larger weight loss in trials, though it is not yet approved or available. If you are weighing your options today, it is worth knowing where the science is heading.

What Steady does with this

Steady tracks the drug, the dose, the day, and your symptoms in the same place, so when you sit down with your prescriber to discuss whether to switch, you are not relying on memory. You are looking at thirty days of patterned data: how often nausea hit, how the weekly weight curve looked, what the protein average was. The decision becomes a comparison, not a guess.

Sources

1. Aronne LJ et al. Tirzepatide vs Semaglutide for Obesity (SURMOUNT-5). NEJM 2025. NEJM
2. Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. NEJM 2022;387:205-216. NEJM
3. Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. NEJM 2021;384:989-1002. NEJM
4. FDA Prescribing Information, Wegovy. Label
5. FDA Prescribing Information, Zepbound. Label

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Medical disclaimer: Articles in the Steady research hub are educational, not medical advice. The choice between medications is your prescriber's call, not ours. See our full medical disclaimer.