Zepbound produced greater average weight loss than the Wegovy injections tested in SURMOUNT-5: 20.2% versus 13.7% over 72 weeks. That is a 6.5-percentage-point difference in adults without diabetes. The trial compared tirzepatide 10 or 15 mg with semaglutide 1.7 or 2.4 mg, not Wegovy tablets or the newer 7.2 mg injection.[3][6]
What each one actually is
Zepbound is the obesity brand name for tirzepatide, made by Eli Lilly. It is a dual agonist: it activates both the GLP-1 receptor and the GIP receptor. (The same molecule is sold as Mounjaro for type 2 diabetes.)
Wegovy contains semaglutide, a GLP-1 receptor agonist made by Novo Nordisk. The US label covers weekly injections, including a 7.2 mg presentation, and daily oral tablets. Weight-management eligibility and other indications differ by formulation: the injection includes age 12 and older with obesity, while tablets are for adults.[6]The injection's MASH indication is for adults with noncirrhotic disease and moderate-to-advanced fibrosis (F2–F3), under accelerated approval.[6] A brand name alone does not specify the dose, route or evidence relevant to a decision.
The separate pivotal trials (not head-to-head)
Each drug earned its approval in its own placebo-controlled trial. In STEP 1, once-weekly semaglutide 2.4 mg produced a mean weight loss of −14.9% at 68 weeks versus −2.4% with placebo.[2] In SURMOUNT-1, tirzepatide at its highest dose produced a mean reduction of −20.9% at 72 weeks versus −3.1% with placebo.[1] Those numbers look decisive — but they come from different trials with different participants. Comparing them suggests an advantage for tirzepatide; it does not prove one.
- Zepbound · tirzepatide 15 mg (SURMOUNT-1, 72 wk)20.9%
- Wegovy · semaglutide 2.4 mg (STEP 1, 68 wk)14.9%
Different trial, different participants
The head-to-head trial: SURMOUNT-5
SURMOUNT-5 provides a direct comparison of specific injection regimens. It randomized 751 adults with obesity but without type 2 diabetes to the maximum tolerated dose of tirzepatide (10 or 15 mg) or the maximum tolerated dose of semaglutide (1.7 or 2.4 mg), once weekly for 72 weeks. At week 72, the least-squares mean weight change was −20.2% with tirzepatide versus −13.7% with semaglutide (P<0.001).[3] Tirzepatide-treated participants were also more likely to reach weight reductions of at least 10%, 15%, 20%, and 25%, and lost more waist circumference. It was an open-label trial funded by Lilly. The result does not establish a ranking for every currently approved formulation or dose.[3][6]
Lilly identifies the main result as a treatment-regimen analysis, rather than an average restricted to people who completed every dose.[8] Missing observations and treatment discontinuation must be handled statistically, so this estimated average is not a guaranteed individual result. For a hypothetical 200 lb starting weight, the reported percentages represent 40.4 lb versus 27.4 lb lost. That 13 lb difference illustrates the percentages, not a prediction for a specific patient.
−20.2%
Zepbound (tirzepatide), mean weight change at 72 wk
SURMOUNT-5, PMID 40353578
−13.7%
Wegovy (semaglutide), mean weight change at 72 wk
SURMOUNT-5, PMID 40353578
751
Participants randomized 1:1 (head-to-head)
SURMOUNT-5
72 wk
Treatment duration
SURMOUNT-5
Cardiovascular outcomes answer a different question
Weight loss is not the only thing that matters. In the SELECT trial, semaglutide 2.4 mg (Wegovy) was studied in 17,604 patients with established cardiovascular disease and overweight or obesity but without diabetes, and it reduced major adverse cardiovascular events — cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke — from 8.0% on placebo to 6.5%, a hazard ratio of 0.80 (95% CI 0.72–0.90, P < 0.001) over a mean 39.8 months of follow-up.[4] The absolute event-rate difference was 1.5 percentage points. Wegovy's current label includes cardiovascular-risk reduction in adults with established cardiovascular disease and overweight or obesity.[6] SELECT compared semaglutide with placebo, not tirzepatide.
Tirzepatide now also has dedicated outcomes evidence: SURPASS-CVOT found it noninferior to dulaglutide for cardiovascular death, heart attack or stroke in people with type 2 diabetes and atherosclerotic cardiovascular disease. Superiority was not established.[7] That result does not show which drug prevents more cardiovascular events in a Zepbound-versus-Wegovy comparison. Zepbound's current label includes adult weight management and moderate-to-severe obstructive sleep apnea in adults with obesity, rather than a cardiovascular-risk-reduction indication.[5]
Side by side
Swipe to see all columns
| Zepbound (tirzepatide) | Wegovy (semaglutide) | |
|---|---|---|
| Mechanism | Dual GIP + GLP-1 agonist | GLP-1 agonist |
| Maker | Eli Lilly | Novo Nordisk |
| SURMOUNT-5 regimen | 10 or 15 mg injection weekly | 1.7 or 2.4 mg injection weekly |
| SURMOUNT-5 mean weight change | −20.2% at 72 weeks | −13.7% at 72 weeks |
| Current formulations | Weekly injection | Weekly injection; daily oral tablet |
| Higher injection option in current label | Maximum 15 mg | 7.2 mg for eligible adults |
| Additional labeled uses | Moderate-to-severe OSA in adults with obesity | CV-risk reduction; injection also has an adult MASH indication |
Side effects and treatment limits
Both drugs can cause gastrointestinal symptoms. In SURMOUNT-5, the most common adverse events in both groups were gastrointestinal — nausea, diarrhea, constipation, vomiting — and most were mild to moderate and clustered during dose escalation.[3] Both labels warn about severe gastrointestinal reactions, pancreatitis, gallbladder disease and dehydration-related kidney injury. Both carry a boxed warning about thyroid C-cell tumors based on rodent findings, with contraindications for a personal or family history of medullary thyroid carcinoma or MEN 2. Neither should be combined with another GLP-1 medicine.[5][6]
Lilly's report of the published SURMOUNT-5 results gives adverse-event treatment-discontinuation rates of 6.1% with tirzepatide and 8.0% with semaglutide, a descriptive absolute difference of 1.9 percentage points. The study was not powered to compare safety and tolerability.[8]A greater average weight reduction is not evidence that a drug is safer for a particular patient. A prescriber should assess medical history and other medicines before selecting a product or dose.
Cost and access
Compare the full cost for the exact prescription and formulation, including medication, visits, laboratory work and follow-up. An introductory offer may not describe the ongoing cost, and a savings program's eligibility is different from an insurer's coverage decision. Request a written estimate and confirm what happens if a dose or product changes. The lower total cost depends on the prescription, coverage and services included.
What should guide the choice?
SURMOUNT-5 favors tirzepatide for average weight loss against the semaglutide injections it tested. It does not answer the comparison with Wegovy's tablet or 7.2 mg injection, and it does not settle cardiovascular superiority or overall safety between the brands. The appropriate formulation and labeled indication, tolerability, ongoing cost and access to clinical follow-up all matter.
For the underlying molecule-level comparison, see our deeper read on tirzepatide vs semaglutide and on the semaglutide weight-loss trials. You can also line the two up feature by feature in our GLP-1 comparison tool.