The SURMOUNT trials of tirzepatide, one by one

Tirzepatide acts on two receptors, GLP-1 and GIP, the second incretin released by the gut after a meal. Eli Lilly's SURMOUNT programme tested it for weight in people with and without type 2 diabetes, after intensive lifestyle change, against withdrawal, and against semaglutide. The diabetes trials, SURPASS, came first and are covered on the head-to-head page.

The results in one table

SURMOUNT-1: the dose response

2,539 adults with a mean weight of 104.8 kg and a mean BMI of 38.0 were randomised equally to 5, 10 or 15 mg or placebo for 72 weeks, including a 20-week climb to dose. The result is the treatment-regimen estimand, counting people who stopped. The Zepbound label sets out the spread at each dose:

The jump from 5 to 10 mg (4.5 points) was much bigger than from 10 to 15 mg (1.4 points). Stopping for adverse events was 4.3%, 7.1% and 6.2% on the three doses, against 2.6% on placebo. Most side effects were gastrointestinal and happened during the climb.

Three years, and diabetes prevention

Participants who had prediabetes at the start of SURMOUNT-1, 1,032 of them, stayed on their assigned dose for 176 weeks and were then followed for 17 weeks off treatment. At three years, weight change was -12.3%, -18.7% and -19.7% on 5, 10 and 15 mg, against -1.3% on placebo. Type 2 diabetes was diagnosed in 1.3% on tirzepatide against 13.3% on placebo, a hazard ratio of 0.07. After 17 weeks off treatment, the figures were 2.4% and 13.7%.

SURMOUNT-2: type 2 diabetes

938 adults with type 2 diabetes and a BMI of 27 or more were randomised to 10 mg, 15 mg or placebo for 72 weeks. Weight fell 12.8% and 14.7%, against 3.2%. As with semaglutide in STEP 2, the effect is smaller than in people without diabetes: 15 mg gave -14.7% here and -20.9% in SURMOUNT-1.

SURMOUNT-3: after a lifestyle programme

Adults first went through a 12-week intensive lifestyle programme. The 579 who lost at least 5% were then randomised to tirzepatide at the highest tolerated dose (10 or 15 mg) or placebo for 72 weeks. Tirzepatide added a further 18.4% loss. The placebo group regained 2.5%. The point of the design: even after a good result from diet and exercise, the drug adds a large effect on top.

SURMOUNT-4: what stopping does

783 adults took tirzepatide for 36 weeks, and the 670 who completed that lead-in had lost a mean of 20.9%. They were randomised to continue or switch to placebo for 52 weeks. Continuing gave a further 5.5% loss. Switching gave a 14.0% regain. 89.5% of those who continued kept at least 80% of their earlier loss, against 16.6% on placebo. Over the full 88 weeks, the totals were -25.3% and -9.9%. The weight regain page covers this in detail.

SURMOUNT-5: against semaglutide

751 adults with obesity and no diabetes received the highest tolerated dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks. Weight change was -20.2% against -13.7%, and waist circumference -18.4 cm against -13.0 cm. The trial was open label and funded by Lilly. See semaglutide vs tirzepatide for what this does and does not settle.

Reading SURMOUNT against STEP

The two programmes look alike on paper: weekly injection, diet and activity advice in both arms, 68 to 72 weeks, a withdrawal trial, a diabetes trial. The differences matter when you compare them. SURMOUNT-1 tested three doses, so it shows a dose response; STEP 1 tested one. SURMOUNT-4 ran a 36-week lead-in before withdrawal and STEP 4 ran 20 weeks, so people in SURMOUNT-4 had lost about twice as much before the drug was stopped. Both report a treatment-policy or treatment-regimen estimand as the main result, which counts people who stopped. Placebo arms lost a similar amount: 2.4% in STEP 1, 3.1% in SURMOUNT-1. Those similarities make the programmes roughly comparable. Only SURMOUNT-5 compares the drugs directly.

What SURMOUNT did not answer

SURMOUNT used Lilly's own product, not compounded tirzepatide. The weight trials did not measure heart attacks or deaths as an outcome. Body composition was measured only in a subgroup, discussed on the lean mass studies page. The titration schedule page explains how the trial doses map onto the label. The master table sets SURMOUNT beside STEP and the newer drugs.

Trials report averages. Your own result is a line on a chart: the dose and the date you changed it, your weight, the side effects that came with each step and, if you have them, your labs. Peptide AI keeps those on one timeline, and the dose log and titration schedule are free. The free GLP-1 tracker page explains what it records, or download the app.