SURMOUNT & SURPASS: What the Trials Really Show

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Mounjaro and Zepbound did not appear from nowhere. Behind tirzepatide — the single drug sold under both names — sits one of the largest and most closely watched clinical-trial programs in modern metabolic medicine: two families of studies, run over years and across tens of thousands of participants. One family, called SURPASS, tested the drug in type 2 diabetes. The other, SURMOUNT, tested it for weight loss. Understanding what these tirzepatide clinical trials found, and just as importantly how they were built, is the clearest way to understand what the drug actually does — and where the honest limits of that evidence lie.

Two Trial Programs, One Drug

Tirzepatide is a single molecule. It reached the market, though, as two separate brand-name products — Mounjaro for type 2 diabetes, and Zepbound for weight management and obstructive sleep apnea — and that split is mirrored in its trials.

A drug is approved for a specific use, not in general. To be approved to treat diabetes, tirzepatide had to be tested in people with diabetes, against diabetes treatments, measuring diabetes outcomes. To be approved for weight management, it had to be tested again — in a different population, against different comparators, measuring weight. Hence two programs. SURPASS is the diabetes program; its results supported the approval of Mounjaro. SURMOUNT is the obesity program; its results supported Zepbound. Our comparison of Mounjaro and Zepbound covers how the two products differ in practice.

What both programs were testing is a drug that works differently from the GLP-1 medications that came before it. Tirzepatide is a dual agonist — it activates two gut-hormone receptors, GIP and GLP-1, rather than GLP-1 alone. The theory, borne out in the trials, was that engaging both pathways would produce larger effects on blood sugar and body weight than engaging one. That is the central idea the SURPASS and SURMOUNT trials were built to test.

The SURPASS Trials: Tirzepatide in Type 2 Diabetes

The SURPASS program was a series of phase 3 trials, numbered SURPASS-1 through SURPASS-5 — with further regional and specialized studies beyond those — each placing tirzepatide against a different comparator so the drug could be judged from several angles.

A few results stand out. SURPASS-2 drew the most attention, because it pitted tirzepatide directly against semaglutide 1 mg — at the time a leading GLP-1 diabetes drug — as an add-on to metformin in nearly 1,900 adults. All three tirzepatide doses produced greater reductions in A1c (the standard measure of long-term blood sugar) and greater weight loss than semaglutide. Across the SURPASS trials, large proportions of participants — up to roughly 90% or more at the higher doses — reached an A1c below 7%, the usual treatment target, and a striking share reached below 5.7%, a level considered outside the diabetic range altogether. Weight loss, although a secondary outcome in a diabetes program, was consistent throughout.

The headline from SURPASS, in short: tirzepatide lowered blood sugar more than the comparators it was tested against, including a then-standard GLP-1 drug.

The SURMOUNT Trials: Tirzepatide for Weight

The SURMOUNT program asked a different question: how much weight does tirzepatide produce in people being treated for obesity?

SURMOUNT-1 was the foundational study — 2,539 adults with obesity, but without diabetes, treated for 72 weeks. The results, published in The New England Journal of Medicine in 2022, were what put tirzepatide on the map: average weight reductions of 16.0% on the 5 mg dose, 21.4% on 10 mg, and 22.5% on 15 mg, against just 2.4% on placebo. Average figures in the 20% range had not been seen before from a medication.

The rest of the program filled in the picture. SURMOUNT-2 tested the drug in people who had both obesity and type 2 diabetes, and — as is consistently seen with these medications — weight loss in that group was somewhat lower, around 12 to 15%. SURMOUNT-3 looked at tirzepatide started after a period of intensive lifestyle change, and SURMOUNT-4 examined what happens with continued treatment versus stopping. SURMOUNT-4 is worth singling out: participants who continued tirzepatide maintained and extended their loss, while those switched to placebo regained a substantial portion of the weight — a finding that frames obesity as a chronic condition needing ongoing treatment, not a course with an endpoint. A separate study, SURMOUNT-OSA, tested tirzepatide in people with obesity and obstructive sleep apnea, and its results supported Zepbound’s approval for that condition.

SURMOUNT-5: The Head-to-Head With Semaglutide

One SURMOUNT trial deserves its own section, because it answered the question patients ask most often: how does tirzepatide compare directly to semaglutide for weight loss?

SURMOUNT-5, announced at the end of 2024, was a head-to-head trial — tirzepatide against semaglutide 2.4 mg, the Wegovy dose — in 751 adults with obesity but without diabetes, over 72 weeks. The result: participants on tirzepatide lost an average of 20.2% of their body weight, compared with 13.7% on semaglutide. Lilly described that as roughly 47% greater relative weight loss, and tirzepatide also came out ahead on the trial’s key secondary measures.

That is a genuine, clean finding, and it is the strongest direct evidence that tirzepatide produces more weight loss on average than semaglutide. But two caveats matter. First, SURMOUNT-5 was an open-label trial — participants and researchers knew which drug was being given — which is a weaker design than a fully blinded study, even if it does not erase the result. Second, and more importantly, “more weight loss on average” is not the same as “the right choice for every person.” Averages conceal wide individual variation; tolerability, side effects, cost and access differ between the two drugs; and many people do very well on semaglutide. Our semaglutide versus tirzepatide comparison works through those trade-offs in full.

What the Trials Showed About Side Effects

A trial program measures more than how well a drug works — it measures what it costs the people taking it. On that score, the SURPASS and SURMOUNT results were consistent, and largely unsurprising.

The most common side effects of tirzepatide, across both programs, were gastrointestinal: nausea, diarrhea, vomiting and constipation. This is the signature of the whole GLP-1 drug class, and tirzepatide was no exception. Two things are worth knowing about how those side effects behaved in the trials. They were mostly mild to moderate — uncomfortable rather than dangerous for most people — and they were concentrated during dose escalation, the period when the dose is being stepped up. Most appeared while the dose was climbing and eased within weeks, and their frequency fell as treatment continued. This is precisely why tirzepatide is started low and increased gradually; our guide to GLP-1 gastrointestinal side effects covers managing them.

Most participants tolerated the drug. A minority did not: in SURMOUNT-1, adverse events led to treatment discontinuation in roughly 4 to 7% of those on tirzepatide across the three doses, compared with about 3% on placebo. Serious adverse events were uncommon, and only modestly more frequent than with placebo. Pancreatitis — a concern often raised with these drugs — was rare in the trials, and not clearly more common with tirzepatide than with placebo.

The honest summary is that tirzepatide’s trial safety profile held no major surprises: meaningful gastrointestinal side effects for many, mostly early and mostly manageable, a small share of people stopping because of them, and a serious-event rate close to placebo. That is a reassuring profile — but “mostly manageable” is not “nothing,” and the side effects are a real part of the experience that the averages above do not capture.

What the Trials Don’t Tell You

Clinical trials are the best evidence we have, and the SURPASS and SURMOUNT programs are unusually large and rigorous. But reading them well means knowing what they do not show.

Trial populations are selected. Participants are screened, enrolled, and meet specific criteria; they are not a perfect cross-section of everyone who will eventually take the drug. Results in a trial population do not always transfer exactly to the general population.

Trials provide support that real life does not. Participants in weight-loss trials receive regular contact, structured guidance and close monitoring as part of the study. Real-world patients usually do not, and real-world weight loss with these drugs is, on average, somewhat lower than the trial headline figures — not because the drug is different, but because the surrounding conditions are. This is also visible in how many people stop treatment within a year outside of a trial setting.

Trials report averages. A figure like “22.5%” is a mean. Behind it are people who lost far more and people who lost far less. The averages are real and useful, but no individual is guaranteed the average.

And some questions are still open. The longer-term cardiovascular outcomes of tirzepatide in obesity — whether it prevents heart attacks and strokes, as has been shown for semaglutide — are the subject of a dedicated ongoing trial, SURMOUNT-MMO, whose results are not yet in. The trial program is large, but it is not finished.

Frequently Asked Questions

What is the difference between SURMOUNT and SURPASS?

They are two trial programs for the same drug, tirzepatide. SURPASS tested it in type 2 diabetes and supported the approval of Mounjaro; SURMOUNT tested it for weight management and obstructive sleep apnea and supported Zepbound.

How much weight did people lose in the SURMOUNT trials?

In SURMOUNT-1, in adults with obesity but without diabetes, average weight loss over 72 weeks was 16.0% on the 5 mg dose, 21.4% on 10 mg, and 22.5% on 15 mg, versus 2.4% on placebo. In people who also had type 2 diabetes, loss was somewhat lower.

Did tirzepatide beat semaglutide in a head-to-head trial?

Yes. In SURMOUNT-5, a head-to-head weight-loss trial, tirzepatide produced an average 20.2% weight loss versus 13.7% for semaglutide 2.4 mg over 72 weeks. SURPASS-2 also found tirzepatide superior to semaglutide 1 mg for blood sugar control in type 2 diabetes.

Are the trial results what I should expect in real life?

Not exactly. Trial participants are selected and receive structured support that most real-world patients do not, so average real-world results tend to be somewhat lower. Trial figures are also averages — individual results vary widely.

Do the trials show tirzepatide prevents heart attacks?

Not yet. A dedicated cardiovascular outcomes trial in obesity, SURMOUNT-MMO, is ongoing, and its results are not yet available. Cardiovascular benefit has been demonstrated for semaglutide, but the equivalent evidence for tirzepatide in obesity is still being gathered.

What side effects did tirzepatide cause in the trials?

The most common were gastrointestinal — nausea, diarrhea, vomiting and constipation — consistent with the GLP-1 drug class. They were mostly mild to moderate and concentrated during dose escalation, easing as treatment continued. In SURMOUNT-1, side effects led roughly 4 to 7% of participants on tirzepatide to stop treatment; serious adverse events were uncommon.

The Bottom Line

Tirzepatide is one of the most thoroughly tested metabolic drugs ever brought to market, and the SURPASS and SURMOUNT programs are why. SURPASS showed it lowering blood sugar in type 2 diabetes more effectively than the comparators it faced, including a standard GLP-1 drug. SURMOUNT showed weight loss in the 15-to-22.5% range in obesity, and SURMOUNT-5 showed it outperforming semaglutide head-to-head on average.

Those are strong results, and they are real. But the honest reading keeps two things in view at once: the evidence for tirzepatide’s efficacy is genuinely impressive, and — at the same time — trial averages are not personal guarantees, real-world results run lower, and the long-term cardiovascular outcomes data in obesity is still being collected. The trials tell you what tirzepatide can do. What it will do for any particular person is a narrower, more individual question — and one for a clinician.

This article is general information, not medical advice. Trial figures reflect published results as of May 2026; treatment decisions should be made with a qualified healthcare provider.