In the only randomised, head-to-head trial that compared the two drugs directly, tirzepatide produced 20.2% mean weight loss at 72 weeks against semaglutide’s 13.7% (Aronne LJ, Horn DB, le Roux CW, Ho W, et al., New England Journal of Medicine, 3 July 2025, DOI 10.1056/NEJMoa2416394). Read that number in the same breath as its two limits: the trial, SURMOUNT-5, was open-label, so participants and investigators both knew which drug each person was taking, and it was funded by Eli Lilly, the company that manufactures tirzepatide. Neither fact makes the result false. Both are reasons to weigh it carefully rather than repeat it as a bare headline.
Below: the trial’s actual design and both drugs’ results with confidence intervals, why the open-label and industry-funded structure matters and why the result still stands anyway, how each drug’s receptor mechanism predicts the outcome, what the trial reported about reaching specific weight-loss thresholds and about side effects, an honest answer on which drug to ask a prescriber about, where investigational retatrutide fits into this comparison and where it does not, and the two medications a licensed prescriber can put you on this week.
Key takeaways
Is tirzepatide more effective than semaglutide?
Yes, in the one randomised trial that compared them directly: tirzepatide produced 20.2% mean weight loss at 72 weeks against semaglutide’s 13.7% (Aronne LJ, Horn DB, le Roux CW, Ho W, et al., NEJM, 2025). The trial was open-label and funded by Eli Lilly, tirzepatide’s manufacturer, which is worth weighing alongside the result.
How much more weight did tirzepatide produce than semaglutide?
A 6.5-percentage-point gap in mean body weight change at 72 weeks: -20.2% on tirzepatide versus -13.7% on semaglutide, both groups on each drug’s maximum tolerated dose (Aronne LJ, Horn DB, le Roux CW, Ho W, et al., NEJM, 2025).
Was the trial biased toward tirzepatide?
It carries two disclosed limits: it was open-label, not blinded, and Eli Lilly, which manufactures tirzepatide, funded it. Neither invalidates the pre-registered primary endpoint, but both are stated plainly on this page rather than left out.
Is Mounjaro the same drug as tirzepatide?
Yes. Tirzepatide is the active medication; Mounjaro is its FDA-approved brand name for type 2 diabetes, and Zepbound is its FDA-approved brand name for weight loss.
Is Ozempic the same drug as semaglutide?
Yes. Semaglutide is the active medication; Ozempic is its FDA-approved brand name for type 2 diabetes, and Wegovy is its FDA-approved brand name for weight loss.
Does retatrutide beat both of them?
Retatrutide produced a larger number, -24.2% at 12 mg, in its own separate phase 2 trial (Jastreboff AM, Kaplan LM, Frías JP, et al., NEJM, 2023), but no published trial has compared retatrutide against tirzepatide or semaglutide directly, and retatrutide remains investigational: it cannot legally be prescribed.
The head-to-head trial
SURMOUNT-5, published by Aronne LJ, Horn DB, le Roux CW, Ho W and colleagues, is the only published randomised trial that put tirzepatide and semaglutide head to head in the same patients. It was a phase 3b, open-label, controlled trial of 751 adults with obesity but without type 2 diabetes, published in the New England Journal of Medicine on 3 July 2025 (DOI 10.1056/NEJMoa2416394, PMID 40353578, registered as ClinicalTrials.gov NCT05822830). Participants were randomised 1:1 to the maximum tolerated dose of either drug, tirzepatide at 10 or 15 mg, or semaglutide at 1.7 or 2.4 mg, both by once-weekly subcutaneous injection, for 72 weeks. The trial’s primary endpoint was percent change in body weight at week 72.
| Endpoint at 72 weeks | Tirzepatide (max tolerated 10 or 15 mg) | Semaglutide (max tolerated 1.7 or 2.4 mg) |
|---|---|---|
| Mean body weight change | −20.2% (95% CI −21.4 to −19.1) | −13.7% (95% CI −14.9 to −12.6) |
| Mean waist circumference change | −18.4 cm (95% CI −19.6 to −17.2) | −13.0 cm (95% CI −14.3 to −11.7) |
Both differences were statistically significant at P<0.001. That threshold means the gap between the two drugs’ results is very unlikely to be chance given how the trial randomised and measured its participants, which is a separate question from whether the trial’s open-label design could have influenced the size of that gap, addressed next.
Why open-label and Lilly-funded matter, and why the result still stands
SURMOUNT-5 is open-label, meaning every participant and every investigator knew which drug, tirzepatide or semaglutide, a given patient was taking, and this is the detail most pages citing its result leave out. Blinding exists to stop knowledge of the assignment from quietly shaping behaviour on either side: a participant who knows they are on the drug widely reported as more effective may adhere to the injection schedule more carefully, and an investigator who knows the assignment may record borderline side effects a little differently. Neither of those effects can be ruled out or measured from the published trial alone.
SURMOUNT-5 was also funded by Eli Lilly, the company that manufactures and sells tirzepatide as Mounjaro and Zepbound. Industry funding of a phase 3 trial of this size is the normal way large randomised trials get run, not a red flag on its own, and it does not retroactively change a pre-registered primary endpoint or the raw numbers 751 participants produced. But the reader deserves to know who paid for the trial that produced the number being quoted, and a company funding a trial that pits its own drug against a competitor’s has an obvious interest in the outcome.
Neither limitation is a reason to treat the -20.2% versus -13.7% result as fake, and neither is a reason to wave the caveats away and repeat the number as if it came from a blinded, independently funded trial. The honest position sits between those two: this is the best evidence available on how the two drugs compare directly, from the only trial that has ever put them in the same study, and it carries a specific, disclosed pair of limits that a full, blinded, independently funded replication would remove.
How they work, and why the mechanism predicts the result
Semaglutide is a GLP-1 receptor agonist: it activates one hormone receptor, GLP-1, involved in appetite suppression and slower stomach emptying. Tirzepatide is a dual GIP and GLP-1 receptor agonist: it activates that same GLP-1 receptor and adds a second one, GIP, which affects insulin response and appetite through a separate pathway. The extra receptor tirzepatide activates is the leading mechanistic explanation researchers point to for the gap SURMOUNT-5 measured, though the trial itself was designed to measure the outcome, not to isolate the mechanism behind it.
| Semaglutide | Tirzepatide | |
|---|---|---|
| Mechanism | GLP-1 receptor agonist | Dual GIP and GLP-1 receptor agonist |
| Brand names | Ozempic (type 2 diabetes), Wegovy (weight loss) | Mounjaro (type 2 diabetes), Zepbound (weight loss) |
| FDA approval status | FDA-approved | FDA-approved |
| Dosing in SURMOUNT-5 | Maximum tolerated 1.7 or 2.4 mg, once weekly, subcutaneous injection | Maximum tolerated 10 or 15 mg, once weekly, subcutaneous injection |
For context only, not as a comparison: retatrutide, still investigational, adds a third receptor, glucagon, on top of the GIP and GLP-1 pathways tirzepatide already activates, which is why it is described as a triple agonist rather than a dual agonist. What that third pathway would mean in a head-to-head trial against either approved drug is unknown, because no such trial has been run. Retatrutide’s own numbers are addressed on their own terms later on this page.
Responder rates
SURMOUNT-5 reports that tirzepatide participants were more likely than semaglutide participants to reach weight-loss reductions of at least 10%, 15%, 20% and 25% of body weight. The trial states that direction plainly, more tirzepatide participants crossed each of those four thresholds, without the exact share of participants at each threshold available in the material this page draws from. Rather than estimate those figures, this page states only what was reported: the direction of the effect at all four thresholds, in tirzepatide’s favor. Read the full responder-rate table in the trial itself (DOI 10.1056/NEJMoa2416394).
Side effects
The most common adverse events in SURMOUNT-5 were gastrointestinal in both the tirzepatide and semaglutide groups, most of them mild to moderate and occurring primarily during dose escalation. That pattern, GI symptoms concentrated early as the dose is stepped up rather than spread evenly across the full 72 weeks, matches what is generally reported for this drug class. No incidence figures broken out by specific side effect and dose are stated on this page, because none are available in the material this page draws from: treat any specific side-effect percentage you see elsewhere attributed to this trial with the same scrutiny this page applies to its own numbers, and check it against the source (DOI 10.1056/NEJMoa2416394).
Which should you ask for
Tirzepatide is the drug with the stronger weight-loss result in the only head-to-head trial that exists, 20.2% versus semaglutide’s 13.7% at 72 weeks, so anyone whose priority is maximum measured weight loss has a specific, sourced reason to ask a prescriber about it. That is not a guarantee of a personal result: SURMOUNT-5 reports a trial average across 751 people, not a promise for any one patient.
Semaglutide has the longer approval and prescribing track record, having reached the market before tirzepatide, and it may be easier to obtain from some prescribers and telehealth providers as a result. For someone who weighs a longer real-world history and broader provider familiarity over the trial’s raw percentage gap, that is a legitimate reason to start there instead.
Neither drug is a self-directed choice: both require a licensed prescriber’s evaluation of your health history, other medications and whether a GLP-1-class or dual-agonist medication is appropriate for you at all before either can be started. The comparison on this page is meant to inform that conversation, not replace it.
Where retatrutide fits
Retatrutide produced a larger weight-loss figure, -24.2% mean change at 12 mg, than either drug’s SURMOUNT-5 result, but that number comes from a separate phase 2 trial with a different design, a different duration and a different patient population, not from a head-to-head study against either approved drug. Jastreboff AM, Kaplan LM, Frías JP and colleagues published that result in the New England Journal of Medicine in 2023, from a double-blind, placebo-controlled trial of 338 adults over 48 weeks (DOI 10.1056/NEJMoa2301972, PMID 37366315, registered as NCT04881760).
Lining that 48-week, 338-person, placebo-controlled figure up against SURMOUNT-5’s 72-week, 751-person, active-comparator figures and calling it a three-way comparison would be exactly the mistake this page is built to avoid: different trial designs, different durations and different populations do not produce numbers that can be set side by side and trusted. Retatrutide also remains investigational: it is not FDA-approved, and it cannot legally be prescribed for weight loss outside the clinical-trial process that is still testing it. Read the full mechanism and trial detail on the retatrutide page.
What you can be prescribed today
Semaglutide and tirzepatide are both FDA-approved and available today from a licensed prescriber after a medical evaluation; retatrutide is not an option at all outside a clinical trial. The providers below evaluate eligibility and prescribe compounded semaglutide or compounded tirzepatide, the same two active ingredients compared on this page.
These providers prescribe tirzepatide and semaglutide, which are FDA-approved. We may earn a commission, and it never changes your price.
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#1
TrimRxPersonalized programs, US pharmacies
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#2
Joi & BlokesHis & hers compounded GLP-1s
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#3
ReadyRxFast approvals on weight-loss meds
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The table below scores all five providers this site reviews against the same published rubric, so you can see how each one’s semaglutide and tirzepatide pricing and track record compare before you pick one.
| # | Provider | Our score | Semaglutide | Tirzepatide | Worth knowing |
|---|---|---|---|---|---|
| 1 | TrimRx | 3.0/5 | from $199/mo | from $349/mo | Price stays flat as the dose escalates. |
| 2 | Joi & Blokes | 2.0/5 | $199/mo, billed quarterly | $299/mo, billed quarterly | First payment is $497 (semaglutide) or $747 (tirzepatide). |
| 3 | ReadyRx | 2.0/5 | $299/mo, or $249/mo prepaid | $399/mo | Refund if you have not lost 5% of baseline weight by 28 weeks. |
| 4 | AltRx | 0.5/5 | $89/mo promotional, $199/mo standard | $149/mo | BBB rates it F for failure to respond to 37 complaints. |
| 5 | Zevay | 0.0/5 | $149/mo | $187/mo | No BBB or Trustpilot profile found as of 16 July 2026. |
Scores are computed from our published rubric, shown in full on each review. Prices verified 16 July 2026: confirm your current price with the provider before you pay.
Sources
Aronne LJ, Horn DB, le Roux CW, Ho W, et al. “Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.” New England Journal of Medicine, 3 July 2025. DOI: 10.1056/NEJMoa2416394. PMID 40353578. Registered as ClinicalTrials.gov NCT05822830. This is the primary source for every SURMOUNT-5 figure on this page.
Jastreboff AM, Kaplan LM, Frías JP, et al. “Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial.” New England Journal of Medicine, 2023;389(6):514-526. DOI: 10.1056/NEJMoa2301972. PMID 37366315. Registered as ClinicalTrials.gov NCT04881760. This is the source for the retatrutide figure referenced above for context only, not as a head-to-head comparison.
Semaglutide vs tirzepatide: frequently asked questions
Is tirzepatide better than semaglutide?
In the only randomised trial that compared them directly, tirzepatide produced more weight loss than semaglutide: 20.2% versus 13.7% mean change at 72 weeks (Aronne LJ, Horn DB, le Roux CW, Ho W, et al., NEJM, 2025). That trial was open-label and funded by Eli Lilly, tirzepatide’s manufacturer, which is worth knowing alongside the result rather than a reason to dismiss it.
How much more weight does tirzepatide help you lose than semaglutide?
A 6.5-percentage-point gap in SURMOUNT-5’s 72-week result: tirzepatide’s mean body weight change was -20.2% against semaglutide’s -13.7%, both groups on each drug’s maximum tolerated dose (Aronne LJ, Horn DB, le Roux CW, Ho W, et al., NEJM, 2025).
Is Mounjaro the same as tirzepatide?
Yes. Tirzepatide is the active medication in both Mounjaro, FDA-approved for type 2 diabetes, and Zepbound, FDA-approved for weight loss. The drug itself is identical; the brand name changes with the approved use.
Is Ozempic the same as semaglutide?
Yes. Semaglutide is the active medication in both Ozempic, FDA-approved for type 2 diabetes, and Wegovy, FDA-approved for weight loss. As with tirzepatide’s two brand names, the drug itself does not change.
Can I switch from semaglutide to tirzepatide, or the other way around?
That decision belongs to a licensed prescriber evaluating your specific case, not to this page. SURMOUNT-5 compared the two drugs in patients starting fresh, not in patients switching mid-treatment, so its results do not directly describe what happens when someone changes from one to the other.
Which has fewer side effects, tirzepatide or semaglutide?
SURMOUNT-5 reports gastrointestinal side effects as the most common in both groups, mostly mild to moderate and occurring primarily during dose escalation, without publishing incidence figures broken out clearly enough in the available material to declare a clean winner. Treat any specific side-effect percentage you see elsewhere attributed to this trial with caution and check it against the source.
Is either tirzepatide or semaglutide FDA-approved for weight loss?
Yes, both are. Semaglutide is FDA-approved for weight loss under the brand name Wegovy, and tirzepatide is FDA-approved for weight loss under the brand name Zepbound. Both also have separate FDA-approved brand names, Ozempic and Mounjaro, for type 2 diabetes.
What about compounded versions of semaglutide or tirzepatide?
Compounded semaglutide and compounded tirzepatide contain the same active ingredients as the FDA-approved brand-name products, but a compounded preparation is not itself an FDA-approved finished product, even when the compounding pharmacy is properly registered. SURMOUNT-5 tested the two drugs directly, not a compounded version of either, so its results describe the active ingredients rather than any specific compounded formulation.
Does the SURMOUNT-5 trial include people with type 2 diabetes?
No. SURMOUNT-5 enrolled 751 adults with obesity who did not have type 2 diabetes, so its results describe weight-loss treatment specifically, not the type 2 diabetes indication both drugs are also approved for.
Why does this page mention retatrutide if it isn’t part of the comparison?
Because readers researching semaglutide versus tirzepatide often ask about retatrutide next. Retatrutide produced -24.2% mean weight loss at 12 mg in its own separate phase 2 trial (Jastreboff AM, Kaplan LM, Frías JP, et al., NEJM, 2023), but it has never been tested head-to-head against tirzepatide or semaglutide, and it remains investigational: no prescriber can legally prescribe it today.