Semaglutide vs Tirzepatide Head to Head: What SURMOUNT-5 Tested and What It Leaves Open for Patients in Brazil

If you take semaglutide and keep hearing that tirzepatide works better, you've probably wondered whether the evidence backs that up. The most direct answer comes from a trial where the two drugs were compared head to head. That trial is SURMOUNT-5. It doesn't settle every question about semaglutide vs tirzepatide, but it gives you a solid base for a conversation with your prescriber.

Why a head-to-head trial is so rare

Most trials of GLP-1 drugs and dual agonists compare a new drug with placebo. Regulators need that comparison to learn whether a drug works at all. Trials that pit two active drugs against each other are therefore unusual, and companies rarely run them.

You may have seen people line up results from different studies, such as SURPASS for tirzepatide and STEP for semaglutide. These cross-trial comparisons look tidy, but they mislead more often than they help. The populations, durations, doses, and designs all differ. A bigger weight number in one study doesn't prove a drug is better when the people and the rules were never the same.

What SURMOUNT-5 actually did

SURMOUNT-5 randomized adults with obesity but without diabetes to receive either tirzepatide or semaglutide. The design was open-label, and treatment lasted about 72 weeks. The results appeared in the New England Journal of Medicine in 2025, and the trial enrolled 751 participants. Confirm the duration and enrollment in the methods section before you repeat them.

Each arm received the highest dose used in the protocol: 15 mg of tirzepatide and 2.4 mg of semaglutide. Participants reached those doses through a stepwise titration, so the dose rose gradually over several months. That path matters, because it shapes how tolerable the treatment felt for each person.

The primary endpoint was the percentage change in body weight from baseline. In the results table of the NEJM article, the mean reduction at the end of treatment was about 20.2% with tirzepatide and about 13.7% with semaglutide. These are averages for each group, not promises for any single person. Open the table yourself to check the exact figures and the variation around them.

Discontinuation deserves as much attention as the weight numbers. The same table reports how many people in each arm stopped treatment because of adverse events. I'd rather you read those exact rates in the table than rely on a summary, since rounding can hide the difference. Put them next to the weight data, because a larger weight loss paired with more people quitting tells a different story.

Where the comparison gets messy

The first complication is the open-label design. Participants and investigators knew which drug each person took. That doesn't make the results invalid, but it can shape expectations and the way side effects get noticed and recorded. Keep this in mind when you interpret small differences.

The second issue is the population. SURMOUNT-5 enrolled people without diabetes, so its results don't transfer automatically to type 2 diabetes. For that situation, the more relevant reference is SURPASS-2, which compared tirzepatide with semaglutide in people with type 2 diabetes. If you take Ozempic for diabetes, the approved indication in its bula also matters, because your glucose goals and medication history count as much as your weight goal.

The third problem is dose. The trial used maximum doses, but many people never reach the top dose in real life. Side effects such as nausea or constipation can slow titration or stop it altogether. A comparison of top doses shows what the drugs can do under trial conditions, not necessarily what you'll reach in a clinic. Ask your prescriber what dose you're on, how quickly you can increase it, and what happens if you need to stay where you are.

Finally, SURMOUNT-5 doesn't answer long-term cardiovascular outcomes, kidney outcomes, or whether one drug is more cost-effective. Its window of about 72 weeks tells us something about weight and tolerability, but nothing about the next decade. Don't let a short-term weight difference stand in for those larger questions.

What the evidence means if you live in Brazil

Start with the label. Mounjaro (tirzepatide) and Ozempic (semaglutide) each carry indications approved by ANVISA, and the indication listed in each bula decides whether a given use is on-label. Look up your exact product in the Bulário Eletrônico using the registration number printed on the box. A carton that looks familiar may belong to a different presentation.

If your prescriber uses a drug outside its approved indication, that's an off-label decision. It can be reasonable in some situations, but it should be discussed openly. Ask why it's being chosen, which alternatives exist, and what evidence supports it. Write the answer down.

Coverage is the next question. The National Supplementary Health Agency (ANS) regulates health plans in Brazil, and its website at gov.br/ans explains the coverage rules. I can't tell you how your plan treats weight-loss use, so ask your operator for a written answer about the specific product and indication.

For cost, compare monthly spending, not the price of one pen. Multiply the number of pens or doses you'd need each month at your target dose by the unit price, then add any supplies. Use the CMED price list or a current pharmacy listing, and write down the date you checked. Readers who want to track these numbers over time can use OzemBlog to keep a dated record instead of relying on memory.

Questions to take to your prescriber about switching

Ask whether switching from semaglutide to tirzepatide fits your goal. You might want more weight loss, better glucose control, fewer side effects, or a lower monthly cost. Each goal points to a different answer, and the trial addresses each one only partly. Also ask which dose you would restart at, according to the label. A switch rarely means picking up where you left off, so confirm the starting dose and titration steps before you change anything.

Then ask what monitoring the transition requires. Find out which measurements matter for you, such as weight, glucose, and gastrointestinal symptoms, and how often to record them. Ask too how long to wait before judging the change. Deciding too early can lead to false conclusions, while waiting too long can mean living with a side effect that should have been addressed sooner.

How to read the evidence without overreacting

When you read any GLP-1 comparison, check the population first. Ask whether the people in the study match you in terms of diabetes, weight, age, and other conditions. Then check the dose, to see whether it reflects what you'd realistically reach. Finally, check the endpoint, to confirm what was measured and whether it matters for your goals. If one of those three doesn't line up with your situation, be cautious about applying the result to yourself.

The practical next step is simple. Bring the SURMOUNT-5 results table and your product's bula to your next appointment, and ask your prescriber to walk through them with you. Keep your own numbers, such as weight, glucose readings, and side effects, in one place. Tracking them in OzemBlog or a similar log turns the appointment into a discussion of your data instead of a guess from memory.

Labels and price lists change over time, and a revised bula or a new CMED listing can alter the indication you're using or the cost you pay each month. To follow those changes, check the CMED price pages and the Bulário Eletrônico on a regular schedule, and read the newer articles on the OzemBlog site, where we update comparisons as labels and prices move.

FAQ

Is tirzepatide proven to be better than semaglutide?

SURMOUNT-5 found greater average weight loss with tirzepatide than with semaglutide in adults with obesity and without diabetes. That's a meaningful direct comparison, but it doesn't cover long-term outcomes, people with type 2 diabetes in the same way, or everyday dosing in clinics.

Can I switch from semaglutide to tirzepatide on my own?

No. Switching should be decided with your prescriber, who can confirm the starting dose, the monitoring you need, and whether the change fits your health conditions and goals.

How do I check whether a Brazilian product is approved for obesity or diabetes?

Read the bula for your exact product and presentation, or search the Bulário Eletrônico of ANVISA using the registration number. Indications differ by brand, so the name on the box isn't enough to know what's approved.

Will my health plan cover tirzepatide or semaglutide for weight loss?

Coverage depends on your specific plan and product, and it isn't something to assume. Ask your plan for a written answer about the exact medicine and indication before you decide.

Sources

• Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5), New England Journal of Medicine, 2025
• Tirzepatide Once Weekly for the Treatment of Type 2 Diabetes (SURPASS-2), New England Journal of Medicine
• Bulário Eletrônico, ANVISA (consulta de bulas por nome ou número de registro)
• Preços de Medicamentos, CMED, ANVISA
• Agência Nacional de Saúde Suplementar (ANS), planos de saúde