On average, 15 mg, though by less than the top of the ladder suggests. In the SURMOUNT-1 trial of 2,539 adults without diabetes, weight fell 20.9% at 72 weeks on 15 mg, 19.5% on 10 mg and 15.0% on 5 mg, against 3.1% on placebo [1]. The step from 5 to 10 mg added 4.5 points; the step from 10 to 15 mg added 1.4.
Those figures describe the dose a person was randomized to and stayed assigned to, which is not how most prescriptions go. In practice most tirzepatide users settle lower, a pattern covered in what dose most people actually reach. The question here is narrower: when a dose is held for the length of a trial, how much more does each rung buy, and what does it cost in side effects?
What the trials measured, dose by dose
SURMOUNT-1 assigned adults with a BMI of 30 or more, or 27 or more with a weight-related complication, to 5 mg, 10 mg, 15 mg or placebo in equal groups [1]. The 72 weeks included a 20-week dose-escalation period, and the main analysis counted every participant whether or not they stopped treatment.
At baseline the average participant weighed 104.8 kg. Applied to that average, the 1.4-point gap between 10 mg and 15 mg comes to roughly 1.5 kg, by this site’s arithmetic rather than the trial’s. The 4.5-point gap between 5 mg and 10 mg comes to about 4.7 kg on the same basis.
The thresholds tell a similar story. A reduction of 5% or more was reached by 85% on 5 mg, 89% on 10 mg and 91% on 15 mg, against 35% on placebo. A reduction of 20% or more was reached by 50% on 10 mg and 57% on 15 mg, against 3% on placebo [1]. The abstract compares each dose with placebo, and it does not report a formal test of 15 mg against 10 mg.
The same shape held over three years. Among the 1,032 participants who also had prediabetes, weight at 176 weeks sat 12.3% below baseline on 5 mg, 18.7% on 10 mg and 19.7% on 15 mg, against 1.3% on placebo [2]. The 5 mg arm fell further behind with time, while 10 mg and 15 mg stayed about one point apart.
People with type 2 diabetes lose less at both doses tested, and the gap between 10 mg and 15 mg stays small. In SURMOUNT-2, weight fell 12.8% on 10 mg and 14.7% on 15 mg at 72 weeks, against 3.2% on placebo [3]. A pooled analysis of seven randomized trials and 4,795 people put the difference from placebo at 8.07 points for 5 mg, 10.79 for 10 mg and 11.83 for 15 mg [4]. Those are differences from placebo, pooled across trials of 12 to 72 weeks that included people with diabetes, so they run lower than SURMOUNT-1’s raw figures.
What the higher dose costs in side effects
The Zepbound label pools SURMOUNT-1 and SURMOUNT-2, listed there as Study 1 and Study 2, and reports stomach side effects by dose [6]. Nausea affected 25% on 5 mg, 29% on 10 mg and 28% on 15 mg, against 8% on placebo. Vomiting rose more steadily, from 8% to 11% to 13%, against 2% on placebo.
Any gastrointestinal adverse reaction was reported by 56% at each of the three doses, against 30% on placebo. Stopping treatment because of those reactions did climb with dose: 1.9% on 5 mg, 3.3% on 10 mg and 4.3% on 15 mg, against 0.5% on placebo [6]. The label states that most nausea, vomiting and diarrhea happened during dose escalation and decreased over time.
One common assumption is that the nausea is doing the work. A post hoc analysis across SURMOUNT-1 to -4 found weight reduction was similar whether participants reported no nausea, nausea alone, or any nausea, vomiting or diarrhea [5]. Those symptoms were associated with up to 3.1% of total weight reduction. Between 1.0% and 10.5% of tirzepatide-treated participants stopped because of gastrointestinal side effects.
The wider picture of what these drugs do to the stomach, and how often, sits in the side effects of a GLP-1.
Why the dose goes up at all, and who decides
Every Zepbound prescription starts at 2.5 mg once weekly for four weeks[6]. The label states that 2.5 mg is for starting treatment and is not approved as a maintenance dose. After four weeks it moves to 5 mg, which is the first dose the label treats as a maintenance option.
From there, any further increase is optional and comes in 2.5 mg steps, each after at least four weeks on the current dose. The label names two factors for the prescriber to weigh: treatment response and tolerability. The recommended maintenance doses are 5 mg, 10 mg or 15 mg, and 15 mg is the maximum for every indication.
Stepping through 2.5, 5, 7.5, 10 and 12.5 mg at four weeks each means 15 mg is reached at week 20 at the earliest. That matches the 20-week escalation period in SURMOUNT-1. Real schedules tend to run slower. In a claims study of 20,998 adults without diabetes, 74.2% were still on less than 10 mg by their sixth prescription fill [7], the pattern behind tirzepatide buyers mostly staying under 10 mg.
When a dose is not tolerated, the label points in a specific direction. It tells the prescriber to consider a lower maintenance dose rather than stopping. Stepping down later is its own question, with a trial behind it, covered in whether a lower dose can hold the weight off.
What this means for a reader weighing the next step
The trials support a plain reading. Moving from 5 mg to 10 mg bought a large average gain, and moving from 10 mg to 15 mg bought a small one, with somewhat more vomiting and stopping along the way. Those are group averages, and individual response varies widely around them, as the spread between strong and modest responders shows.
Timing matters as much as the rung. Someone four months in has not yet had the time a trial allowed, and how long a GLP-1 takes to work sets out what early progress does and does not predict. Where weight has stopped moving on a stable dose, the other explanations are in why some people do not lose weight.
All of these figures come from branded tirzepatide in controlled trials. Compounded tirzepatide is not FDA-approved and was not what these trials tested, so the figures describe the approved product. The price side of climbing the ladder is covered in whether tirzepatide is worth the extra cost.