SURMOUNT-5: What the Head-to-Head Trial Actually Showed
SURMOUNT-5 was the first direct trial comparing tirzepatide and semaglutide for weight loss. At 72 weeks, tirzepatide produced about 20.2% mean weight reduction versus about 13.7% for semaglutide — a meaningful gap, though individual results vary.
- SURMOUNT-5 directly compared tirzepatide (Zepbound) and semaglutide (Wegovy) head-to-head.
- At 72 weeks: ~20.2% mean weight reduction with tirzepatide vs ~13.7% with semaglutide.
- Tirzepatide's dual GIP/GLP-1 mechanism is the leading explanation for the larger effect.
- Trial averages do not predict any one person's result; tolerability and cost also matter.
What SURMOUNT-5 was
For years, comparisons between tirzepatide and semaglutide relied on cross-trial inference — comparing separate studies with different participants, which is statistically unreliable. SURMOUNT-5 changed that by randomizing participants directly to one drug or the other, the gold standard for a fair comparison.
The trial enrolled adults with obesity, or overweight with a weight-related complication, and titrated each drug to its maximum tolerated dose over the study period. Because both arms were run under the same protocol with the same population, the difference in outcomes can be attributed to the drugs themselves rather than to differences in study design.
The results at 72 weeks
At 72 weeks, tirzepatide produced roughly a 20.2 percent mean reduction in body weight, compared with roughly 13.7 percent for semaglutide. That gap of about six and a half percentage points is clinically meaningful: for a person weighing 100 kilograms, it is the difference between losing about 14 kilograms and about 20 kilograms on average.
It is important to read these as averages across a population, not guarantees. A substantial share of semaglutide users lost more than the tirzepatide average, and some tirzepatide users lost less than the semaglutide average. Response varies with adherence, dose tolerance, diet, activity, and individual biology. The trial tells you which drug tends to produce more weight loss, not what you personally will lose.
| Outcome | Tirzepatide | Semaglutide |
|---|---|---|
| Mean weight reduction | ~20.2% | ~13.7% |
| Receptor targets | GIP + GLP-1 | GLP-1 only |
| Brand studied | Zepbound | Wegovy |
| Applies to compounded? | No | No |
Why tirzepatide produced more
The leading explanation is mechanism. Semaglutide activates a single incretin receptor, GLP-1. Tirzepatide activates two: GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). The dual action appears to produce greater appetite suppression and metabolic effect for many people, which is consistent with tirzepatide's larger average results across the SURMOUNT programme, not just SURMOUNT-5.
This does not make tirzepatide universally better. Side-effect profiles overlap heavily, some people tolerate one molecule better than the other, and tirzepatide costs more both as brand and compounded. The mechanism explains the efficacy edge; it does not settle the choice for an individual patient.
| Concept | What it means |
|---|---|
| Mean reduction | The average across all participants, not a guarantee |
| Individual variation | Many users fall well above or below the mean |
| Brand vs compounded | Trial evidence applies only to the FDA-approved product studied |
What it means for your decision
SURMOUNT-5 strengthens the case that tirzepatide is the more effective weight-loss molecule on average. But the decision between them is clinical and personal. If maximum average weight loss is the priority and cost and tolerability allow, tirzepatide has the stronger head-to-head evidence. If cost is the constraint, semaglutide is cheaper and still produced substantial, clinically significant loss.
Neither compounded version carries this trial evidence: SURMOUNT-5 studied the FDA-approved brand products, and results should not be assumed to transfer to compounded formulations. Discuss the trade-off with a prescriber who knows your history.
Frequently asked questions
Is tirzepatide better than semaglutide?
On average for weight loss, SURMOUNT-5 showed tirzepatide produced more (about 20.2% vs 13.7% at 72 weeks). But tolerability, cost, and individual response mean it is not automatically the right choice for everyone.
Does this apply to compounded versions?
No. SURMOUNT-5 studied brand Zepbound and Wegovy. Compounded formulations have no formulation-specific trial evidence, and results should not be assumed to transfer.
What was the mean weight loss difference?
Roughly 20.2% with tirzepatide versus 13.7% with semaglutide at 72 weeks — about a six-and-a-half percentage point gap on average.
Sources
- Clinical trials via NEJM (STEP, SELECT, SURMOUNT, SURPASS).
- SURMOUNT-5 head-to-head trial results, 2025.
- FDA — human drug compounding and GLP-1 status.
The numbers behind this page
The tirzepatide price range, stated precisely
Standard-dose compounded tirzepatide runs $139 to $399 a month across the 12 programmes we can price, with a median of $298. The spread between cheapest and dearest is $230 a month, or $2,760 across a year, for a molecule that is chemically identical in every case.
The cheapest verified figure is NexLife at $139 on its 12-month plan; Found follows at $169 (12-month prepaid). Half the market sits below $298 and half above it, which makes the median a more useful reference point than the cheapest figure when judging whether a quote is reasonable.
3 programmes additionally advertise a tirzepatide microdose, the cheapest at $147 a month. Those figures are excluded from the range above. A microdose sits below every dose studied in the pivotal trials, so including it would compare two different things and would make the market look cheaper than it is at a therapeutic dose.
Three structural facts move a bill more than the headline rate. Whether the price is flat across covered doses or rises as you titrate. Whether a membership is billed separately from medication. And whether the advertised figure requires prepaying six or twelve months, which lowers the monthly number by transferring risk to you at exactly the point you are least certain you will continue.
What we do not claim in tirzepatide
The tirzepatide figures on this page span $139 to $399 a month across 12 programmes.
We do not claim these prices will hold. Compounded pricing moves within weeks, and a figure without a capture date is not a fact. We do not claim a compounded preparation is equivalent to an approved product: it is not FDA-approved, is not therapeutically equivalent to any brand-name product, and FDA does not review it for safety, effectiveness or manufacturing quality before marketing.
And we do not claim to be a clinical resource. Which molecule suits you, at what dose, and whether treatment is appropriate at all are questions for a prescribing clinician who has your history. This is price research, and it is only useful once those questions are settled.
Reading the price against the market
What the plan term is worth
Standard-dose tirzepatide spans $139 to $399 a month across 12 programmes we can price, a spread of $260.
Several programmes publish two prices: the advertised rate, which requires a commitment, and the month-to-month rate, which does not. The gap between them is the price of flexibility, and it is rarely presented that way.
Compounded medication is generally not refundable once shipped, and most discontinuation happens in the first three months — precisely the window a twelve-month prepayment covers. Committing at signup and committing after reaching a dose you tolerate are materially different decisions, even though the advertised rate is identical.
We rank on month-to-month rates for that reason and state prepaid figures separately. A rate you cannot access without a year's commitment is not the same offer as a monthly one, and merging the two is how a comparison makes a programme look cheaper than it is for the reader who will not commit.
What the plan term is worth
Standard-dose tirzepatide spans $139 to $399 a month across 12 programmes we can price, a spread of $260.
Several programmes publish two prices: the advertised rate, which requires a commitment, and the month-to-month rate, which does not. The gap between them is the price of flexibility, and it is rarely presented that way.
Compounded medication is generally not refundable once shipped, and most discontinuation happens in the first three months — precisely the window a twelve-month prepayment covers. Committing at signup and committing after reaching a dose you tolerate are materially different decisions, even though the advertised rate is identical.
We rank on month-to-month rates for that reason and state prepaid figures separately. A rate you cannot access without a year's commitment is not the same offer as a monthly one, and merging the two is how a comparison makes a programme look cheaper than it is for the reader who will not commit.
Questions this page answers
Does compounded tirzepatide cost more at higher doses?
At the programmes listed here the monthly price is flat across covered doses; what changes the figure is the plan term, not the dose. Dose-tiered pricing does exist elsewhere in this market, so confirm at checkout.
Why is microdosed tirzepatide cheaper?
Because it is less medicine. 3 programmes advertise a tirzepatide microdose, the cheapest at $147 a month. A microdose sits below every dose studied in the pivotal trials, so it is not a cheaper route to the result those trials measured.
What is the cheapest compounded tirzepatide?
NexLife at $139 a month at a standard therapeutic dose on the 12-month plan ($1,668 total), captured 2026-09-04. 6-month $149; 3-month $159; month-to-month $169. No membership fee, flat at every covered dose. Verified. The next-cheapest is Found at $169, which requires prepaying twelve months (Provider Reported).
What does compounded tirzepatide normally cost?
$139 to $399 a month across 12 programmes, with a median of $298. Half the market sits either side of that median, which makes it a better reference than the cheapest figure when judging a quote.