SURMOUNT-1: Tirzepatide's 20.9% and What Sits Behind It
Last verified May 2026 · 3 · Finished; headline results reported · NCT04184622 ↗
Tirzepatide agonizes two receptors rather than one, adding GIP to GLP-1, and SURMOUNT-1 is where that translated into a number nobody could ignore. Over 72 weeks the top dose delivered roughly a fifth of body weight, in a population selected the same way STEP-1's was: BMI 30 or above, or 27 with a weight-related complication, diabetes excluded. The exclusion is worth holding onto — SURMOUNT-2 ran the same drug in people with type 2 diabetes and reported −14.7%, which is a large result and a materially smaller one. Comparing SURMOUNT-1 against STEP-1 is the comparison most people make, and it was later run properly as a head-to-head in SURMOUNT-5.
- Enrollment
- 2,539
- Duration
- 72 weeks in the main phase, the first 20 of them spent stepping the dose up; people with prediabetes stayed on and were followed to week 176
- Drug
- Tirzepatide
- Population
- Adults 18 and over with a BMI of 30 or more — or 27 or more if a weight-related complication came with it, meaning high blood pressure, abnormal cholesterol, sleep apnea or established heart disease. Type 2 diabetes was an exclusion. Average starting weight 104.8 kg at an average BMI of 38.0, with 94.5% at a BMI over 30, and prediabetes present in roughly four participants in ten.
Primary endpoint
How much body weight came off over 72 weeks
Treatment arm
-20.9% (95% CI -21.8 to -19.9)
Comparator
-3.1% (95% CI -4.3 to -1.9)
Treatment difference: Placebo-subtracted -17.8 percentage points at 15 mg; P<0.001 for all three doses vs placebo
★ The biggest weight reduction any obesity trial had produced when it published, and the three doses lined up in order: 5 mg reached 15.0%, 10 mg reached 19.5%, and 15 mg reached 20.9%. The figure everyone quotes belongs to the top dose alone.
Secondary endpoints
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| Weight lost on the two lower doses ⚠ Worth knowing if cost or side effects keep you off the top dose: 5 mg gets you about 15%, which is roughly where semaglutide's pivotal trial landed. | 5 mg: -15.0% (95% CI -15.9 to -14.2); 10 mg: -19.5% (95% CI -20.4 to -18.5) | -3.1% (95% CI -4.3 to -1.9) | Placebo-subtracted -11.9 percentage points at 5 mg and -16.4 at 10 mg; P<0.001 for both |
| Lost at least 5% of body weight Almost everyone on the drug cleared the threshold clinicians treat as meaningful. ⚠ So did 35% on placebo, which is the counseling and the calorie deficit both arms received. | 5 mg: 85%; 10 mg: 89%; 15 mg: 91% | 35% | Odds ratio favored every tirzepatide dose; P<0.001 |
| Lost at least a fifth of body weight ★ More than half the top-dose group got into territory that used to require surgery. This is the single most consequential row in the table for how the market now talks about these drugs. | 10 mg: 50%; 15 mg: 57% | 3% | P<0.001 for both 10 mg and 15 mg vs placebo |
| Inches off the waist Nearly 20 cm, close to 8 inches, at the top dose. | -19.9 cm (5 mg: -14.6, 10 mg: -19.4, 15 mg: -19.9) | -3.4 cm | Placebo-subtracted -16.5 cm at 15 mg |
| Top blood-pressure number About 7 points beyond placebo — the sort of change a low-dose blood-pressure tablet added to existing treatment would produce. | -8.1 mmHg (pooled 5/10/15 mg) | -1.3 mmHg | Placebo-subtracted -6.8 mmHg |
| Fasting insulin level Nearly halved. This is the clearest sign in the table that the drug is doing something to insulin resistance rather than only removing weight. | -46.9% (pooled 5/10/15 mg) | -9.7% | Placebo-subtracted -37.2 percentage points |
| Triglycerides, a blood fat Down over a quarter against 6% on placebo. | -27.6% (pooled 5/10/15 mg) | -6.3% | — |
| LDL, the cholesterol that drives artery disease ⚠ Barely moved — about 7%. If lowering LDL is the goal, this class is not the tool, and a statin is. | -6.9% (pooled 5/10/15 mg) | -0.9% | — |
| HDL, the other cholesterol Up about 8%, in the direction usually considered favorable. | +7.9% (pooled 5/10/15 mg) | +0.3% | — |
| Three-month average blood sugar ⚠ Nobody here had diabetes, so this is a shift within the normal range — but with about 40% of the group carrying prediabetes, it is the thread the week-176 finding below picks up. | -0.51 percentage points (5 mg: -0.40, 10 mg: -0.49, 15 mg: -0.51) | -0.07 percentage points | — |
Adverse events
| Event | Treatment rate | Comparator rate |
|---|---|---|
| Nausea Mostly mild to moderate, and bunched into the 20 weeks while the dose was climbing. These rates come from the registry across the full trial, not just the first 72 weeks. | 25.4% (5 mg), 34.1% (10 mg), 31.9% (15 mg) | 9.8% |
| Diarrhea Roughly three times the placebo rate at every dose. | 20.3% (5 mg), 22.5% (10 mg), 23.7% (15 mg) | 7.9% |
| Constipation ★ Ran lower at the top dose than the low one — the opposite of nausea. Side effects in this class do not all rise together with the dose. | 17.9% (5 mg), 18.4% (10 mg), 12.7% (15 mg) | 5.9% |
| Vomiting Rose steadily with dose, from about 9% to about 13%, against under 2% on placebo. | 9.2% (5 mg), 11.6% (10 mg), 12.9% (15 mg) | 1.9% |
| Dyspepsia | 9.4% (5 mg), 10.1% (10 mg), 11.7% (15 mg) | 4.8% |
| Loss of appetite Recorded as a side effect, though it is how the drug works rather than something going wrong. | 9.5% (5 mg), 11.8% (10 mg), 8.7% (15 mg) | 3.4% |
| Hair loss ★ Roughly 5% against 1% on placebo, and mostly in women. It generally passes, and it tracks how fast weight is coming off rather than the drug itself — the same thing happens after bariatric surgery. | 5.2% (5 mg), 5.0% (10 mg), 5.9% (15 mg) | 1.1% |
| Reaction where the injection went in Uncommon, but far more frequent than the 0.3% seen on placebo injections. | 2.9% (5 mg), 5.7% (10 mg), 4.6% (15 mg) | 0.3% |
| Stopped the drug because of a side effect Between 4% and 7% depending on dose, against 2.6% on placebo, measured over the 72-week main period. | 4.3% (5 mg), 7.1% (10 mg), 6.2% (15 mg) | 2.6% |
| Serious adverse events of any kind Close to the placebo rate at every dose, and not clustered in any one body system. | 9.0% (5 mg), 9.4% (10 mg), 7.9% (15 mg) | 8.2% |
Subgroup analyses
- People who already had prediabetes, followed all the way to week 176: Still 22.9% below starting weight at week 176 on 15 mg, against 2.1% on placebo; type 2 diabetes developed in 1.2% of those on tirzepatide against 12.6% of those on placebo
★ The most important finding on this page after the headline. Roughly 90% fewer people crossed into diabetes. That is the evidence for saying these drugs change where the disease goes, not just what the scale says.
- Whether the weight stayed off past 72 weeks: 22.9% below baseline at week 176 on 15 mg — effectively unchanged from the 22.5% the same cohort showed at week 72
⚠ Read the condition attached: they were still taking it. SURMOUNT-4 is the trial that shows what stopping does.
Clinical significance
This trial is why tirzepatide is the default request in a lot of consultations, and why Zepbound commands the pricing it does. It should be read alongside two things it does not contain. There is no cardiovascular outcome here — SURPASS-CVOT does not read out until 2027, so the event-reduction evidence semaglutide has from SELECT is not yet matched. And the 20.9% belongs to the 15 mg maintenance dose reached through a six-step titration; people who stop climbing earlier, for tolerability or for cost, are not at that number. ⛔ Compounded tirzepatide was not in this trial, and the concentration in a compounded vial is set by the pharmacy rather than by a protocol.
Who sells tirzepatide, and for how much
This trial tested Tirzepatide. Across the 556 sellers on this register, 253 publish a standing monthly cash price for compounded tirzepatide, from $99 a month, with a median of $240.
⛔ None of those sellers was in this trial. A compounded preparation is not the product studied here: no agency has reviewed that specific preparation for safety, effectiveness or manufacturing quality, and its concentration is set by whichever pharmacy filled it. The result above is the strongest evidence available for tirzepatide and it was generated on something else. Every seller, with its price record.
Frequently Asked Questions
References
- 1.Jastreboff AM, Aronne LJ, Ahmad NN, et al.; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity N Engl J Med. 2022. PMID: 35658024.
- 2.Eli Lilly and Company. Study Results: A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight (SURMOUNT-1, NCT04184622) ClinicalTrials.gov. 2024. https://clinicaltrials.gov/study/NCT04184622?tab=results
- 3.U.S. Food and Drug Administration. FDA Approves New Medication for Chronic Weight Management (Zepbound, tirzepatide) FDA Press Announcement. 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management
- 4.Wilding JPH, Batterham RL, Calanna S, et al.; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP-1) N Engl J Med. 2021. PMID: 33567185.
- 5.Aronne LJ, Sattar N, Horn DB, et al.; SURMOUNT-4 Investigators. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial JAMA. 2024. PMID: 38078870.