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SURMOUNT-5 Results: Tirzepatide vs Semaglutide

Creator: Priya Raman, Health Writer
Published: 2026-09-24

SURMOUNT-5 put 751 adults without diabetes on tirzepatide or semaglutide for 72 weeks. They lost an average of 20.2% and 13.7% of their body weight, and the comparison has limits worth knowing.

Priya Raman, Health Writer September 24, 2026 7 min read

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The short version

SURMOUNT-5 randomized 751 adults with obesity but without diabetes to the highest tolerated weekly dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks, in an open-label trial funded by Lilly.
Average weight change was −20.2% with tirzepatide versus −13.7% with semaglutide, a 6.5-point gap; waist size fell 18.4 cm versus 13.0 cm.
At least 15% weight loss occurred in 64.6% of the tirzepatide group and 40.1% of the semaglutide group; at least 25% in 31.6% versus 16.1%.
Nausea was nearly identical (43.6% vs 44.4%), vomiting was lower on tirzepatide (15.0% vs 21.3%), and 6.1% versus 8.0% stopped treatment because of side effects.
SURMOUNT-5 did not test the 7.2 mg semaglutide dose the FDA added in March 2026, and a separate trial of that dose cannot stand in for a head-to-head result.
The trial studied branded products; through Promise both molecules are dispensed as compounded medications, which is different from an FDA-approved product: the formulations offered here are not FDA-approved.

The SURMOUNT-5 results in one line: after 72 weeks, adults on tirzepatide had lost an average of 20.2% of their body weight, compared with 13.7% for adults on semaglutide. The trial followed 751 adults with obesity who did not have diabetes and put the two weekly shots side by side at their weight-loss doses. Those are group averages, not a prediction for any one person.

What question did the SURMOUNT-5 trial ask?

Most obesity trials compare a drug with a placebo, a look-alike shot with no medicine in it. SURMOUNT-5 compared two real medicines: tirzepatide, the molecule in Zepbound and Mounjaro, and semaglutide, the molecule in Wegovy and Ozempic. At the highest dose each person could handle, which one lowers weight more?

Louis Aronne and colleagues published the answer in the New England Journal of Medicine in May 2025, and the trial is registered as NCT05822830. Eli Lilly, which makes tirzepatide, paid for it, and seven of the paper's eleven authors worked for Lilly.

It was open-label, meaning everyone knew which drug each person was taking. A scale is hard to fool, but knowing the drug can still shape behavior, side-effect reporting and who drops out. A blinded trial guards against that; this one didn't.

Who was in SURMOUNT-5, and who was left out

The volunteers, all in the United States and Puerto Rico, averaged about 45 years old; roughly two in three were women, and they started at an average of 113 kg, about 249 pounds, with an average BMI (a height-to-weight screening number) of 39.4 (Shukla et al., Diabetes, Obesity and Metabolism 2026).

To join, people needed a BMI of at least 30, or 27 plus a condition such as high blood pressure or sleep apnea. The registry lists who was kept out, including anyone with diabetes, past pancreatitis, a family or personal history of medullary thyroid cancer (a rare thyroid tumor), or recent serious depression.

The diabetes exclusion matters most: these numbers describe people without it. An earlier trial, SURPASS-2, compared the two drugs in type 2 diabetes at a lower semaglutide dose, and tirzepatide vs semaglutide covers both trials.

Doses rose one step every four weeks, toward 15 mg of tirzepatide or 2.4 mg of semaglutide; anyone who couldn't tolerate the top step stayed at 10 mg or 1.7 mg. That's what "maximum tolerated dose" means here. Most got at least one top-step dose (89.3% on tirzepatide, 92.8% on semaglutide), according to Lilly's release on the published results. Those were trial assignments; a prescriber sets an individual's dose.

How the trial measured weight loss

The primary endpoint, the main result chosen before the trial began, was the percentage change in body weight at week 72. Key secondary endpoints were the share of people losing at least 10%, 15%, 20% and 25%, and the change in waist size. The headline analysis counted everyone in their assigned group, including people who stopped early, which is more realistic than counting only people who took every dose.

SURMOUNT-5 results: tirzepatide vs semaglutide by the numbers

At week 72	Tirzepatide (10 or 15 mg)	Semaglutide (1.7 or 2.4 mg)
Average weight change	−20.2% (about 50 lb)	−13.7% (about 33 lb)
Average waist change	−18.4 cm (7.2 in)	−13.0 cm (5.1 in)
Lost at least 10%	81.6%	60.5%
Lost at least 15%	64.6%	40.1%
Lost at least 20%	48.4%	27.3%
Lost at least 25%	31.6%	16.1%

The gap was 6.5 percentage points, with a 95% confidence interval (the range the true difference most likely falls in) of 4.9 to 8.1, per the registry results. The threshold shares are the paper's secondary results, also listed in Lilly's release.

Put plainly: the tirzepatide group lost about a fifth of its starting weight on average, the semaglutide group about a seventh. Roughly two in three on tirzepatide crossed 15%, against two in five on semaglutide.

You may see this called "47% more weight loss." That's relative: 20.2 is about 47% bigger than 13.7. The absolute gap, 6.5 points of body weight, shows the real size of the difference.

Side effects in SURMOUNT-5

Stomach and bowel problems led the list on both drugs; the paper reported that most were mild to moderate and came mainly while doses were climbing. These rates are from the results posted to ClinicalTrials.gov for the 750 people who got at least one dose.

Event	Tirzepatide	Semaglutide
Nausea	43.6%	44.4%
Constipation	27.0%	28.5%
Diarrhea	23.5%	23.4%
Vomiting	15.0%	21.3%
Acid reflux (GERD)	6.1%	10.6%
Injection-site reaction	8.6%	0.3%
Hair loss	8.3%	6.1%
Serious adverse events	4.8%	3.5%

Nausea, diarrhea and constipation were nearly even. Vomiting and reflux were less common on tirzepatide; injection-site reactions and hair loss, more common. Stopping treatment because of side effects happened in 6.1% on tirzepatide versus 8.0% on semaglutide, and Lilly's release notes the study wasn't sized to compare the two drugs' safety. No deaths were reported.

What critics and later studies said

The semaglutide ceiling moved. SURMOUNT-5 capped semaglutide at 2.4 mg, the top weight-loss dose while it ran. On March 19, 2026, the FDA added a 7.2 mg Wegovy dose, labeled Wegovy HD (the agency's letter). In its own trial, STEP UP, average weight change was −18.7% on 7.2 mg versus −15.6% on 2.4 mg (Wharton et al., Lancet Diabetes & Endocrinology 2025). That trial had no tirzepatide group, so its 18.7% can't be set beside 20.2% as a new head-to-head result.

The ads ended up in court. As of September 22, 2026, the day this article was written, Novo Nordisk's lawsuit over Lilly's comparative ads was undecided. Novo filed it on July 21, 2026, arguing that ads built on SURMOUNT-5 mislead by leaving out the 7.2 mg dose. The judge heard Novo's request for a preliminary injunction, a temporary order pausing the ads, on August 27 and 28 over Lilly's opposition, then reserved decision; the court docket showed no ruling through its latest filing, dated September 1. The lawsuit explainer covers what the case can decide.

Independent reviews agree on weight, with a safety caveat. As of September 22, 2026, the day this article was written, two independent reviews from the past month had weighed in. A meta-analysis (a study that pools other studies) published August 30 combined ten randomized and real-world comparisons covering 41,381 people and found more weight loss with tirzepatide, and more serious adverse events, 5.7% versus 2.9%, though only three studies reported those (Paccola et al., Clinical Obesity 2026). A September 1 review in Annals of Internal Medicine reached the same weight conclusion (Moiz et al., 2026).

Weight isn't the whole story. SURMOUNT-5 measured weight and waist size, not heart attacks, strokes or deaths, so it can't rank the drugs on long-term health.

What SURMOUNT-5 means for a person

For adults without diabetes, SURMOUNT-5 is the most direct comparison available: at these doses, tirzepatide lowered weight more on average. It can't tell anyone which drug they'll respond to or tolerate, and it didn't test switching. Semaglutide has the longer prescribing history, and brand-level differences such as labels and approved uses live in Zepbound vs Wegovy. For other common misreadings of tirzepatide, see tirzepatide myths.

What it can't say about compounded versions

The trial studied branded products. Through Promise, tirzepatide and semaglutide are dispensed as compounded medications, which is different from an FDA-approved product: the formulations offered here are not FDA-approved. The FDA says it does not verify compounded drugs' safety, effectiveness or quality before marketing, so SURMOUNT-5's averages can't show a compounded preparation will perform the same way.

A licensed provider may still prescribe a compounded formulation; that decision is between the patient and the doctor. At Promise, a licensed provider reviews every request, and not everyone qualifies.

Reading the headline number well

SURMOUNT-5 is solid evidence when its details stay attached: adults without diabetes, the highest tolerated dose, 72 weeks, an open-label design and a company sponsor. Strip those away and 20.2% versus 13.7% becomes a slogan. SURMOUNT-1 results walks through tirzepatide's earlier placebo-controlled trial the same way.

Common questions

What were the SURMOUNT-5 results?

At week 72, average weight change was −20.2% with tirzepatide and −13.7% with semaglutide in 751 adults with obesity but without diabetes. Waist size fell 18.4 cm versus 13.0 cm, and 64.6% of the tirzepatide group lost at least 15% of body weight, compared with 40.1% on semaglutide. These are group averages from one open-label trial, not a forecast for one person.

What doses were used in SURMOUNT-5?

Each person was assigned the highest dose they could tolerate: tirzepatide 10 or 15 mg once a week, or semaglutide 1.7 or 2.4 mg once a week, reached by stepping up every four weeks. Most reached the top step. The trial did not include the 7.2 mg semaglutide dose the FDA added in March 2026. A prescriber sets any individual's dose.

Were side effects different between tirzepatide and semaglutide in SURMOUNT-5?

Mostly similar. In the registry results, nausea affected 43.6% on tirzepatide and 44.4% on semaglutide, and diarrhea and constipation were close too. Vomiting (15.0% vs 21.3%) and acid reflux were less common on tirzepatide, while injection-site reactions (8.6% vs 0.3%) were more common. Stopping for side effects occurred in 6.1% versus 8.0%. The trial was not sized to compare safety.

What does open-label mean in SURMOUNT-5?

It means participants and study staff knew which medicine each person was taking. That doesn't cancel the weight result, which came from a scale, but knowing the drug can shape behavior, side-effect reporting and who drops out. A blinded trial, where nobody knows the assignment, guards against that. SURMOUNT-5 did not have that protection, which is one reason to read it with care.

Did SURMOUNT-5 include people with diabetes?

No. People with diabetes were excluded, so the results describe adults with obesity, or with overweight plus a weight-related condition, who did not have diabetes. The earlier head-to-head trial in type 2 diabetes, SURPASS-2, used a lower semaglutide dose. Carrying SURMOUNT-5's numbers over to someone with diabetes stretches the trial beyond the people it actually studied.

Did SURMOUNT-5 test compounded tirzepatide or semaglutide?

No. FDA-approved versions of both molecules exist, but the compounded formulations offered here are not FDA-approved. SURMOUNT-5 used branded products under a controlled research protocol, so its averages cannot show that a compounded preparation will give the same result. A licensed provider decides whether either formulation is appropriate for a particular person.