Tirzepatide carries the larger headline in obesity medicine, and buyers pay a premium for it on almost every price board. That headline is not one number. It is a dose-response curve with roughly six percentage points between its bottom rung and its top, and the rung a seller is quoting is rarely stated next to the price on the tirzepatide board.
The dose decides the answer
SURMOUNT-1 enrolled 2,539 adults with a body-mass index of 30 or higher, or 27 or higher with at least one weight-related complication. Anyone with diabetes was excluded. They were assigned to once-weekly tirzepatide at 5 mg, 10 mg or 15 mg, or to placebo, for 72 weeks. Mean body weight at entry was 104.8 kg and mean body-mass index was 38.0.[1]
Mean change at week 72 was −15.0% at 5 mg (95% CI, −15.9 to −14.2), −19.5% at 10 mg (−20.4 to −18.5) and −20.9% at 15 mg (−21.8 to −19.9), against −3.1% on placebo.[1] Those are four separate randomized arms, not four stages of one schedule, so reaching the top figure means being assigned and held at the top dose for the full period. What the climb to that dose involves is set out in the titration article.
The thresholds under the averages
A mean says nothing about where any one person lands, and the trial published the distribution. A reduction of 5% or more was reached by 85% at 5 mg, 89% at 10 mg and 91% at 15 mg, against 35% on placebo.[1] The expected-loss tool puts each of those arms against a starting weight, alongside the share of the arm that did not reach the threshold.
The threshold that separates this molecule from most of what preceded it is 20%. That was reached by 50% of the 10 mg group and 57% of the 15 mg group, against 3% on placebo.[1] Turned around, more than two in five participants on the highest dose did not reach 20% after 72 weeks of injections. Nothing measured at baseline told anyone in advance which side of that line they would end on.
The top rung costs something
Adverse events led to discontinuation in 4.3% of the 5 mg group, 7.1% at 10 mg and 6.2% at 15 mg, against 2.6% on placebo. The most common were gastrointestinal, mostly mild to moderate, and they clustered in the escalation period.[1] Notice that the discontinuation rate does not climb tidily with the dose: the middle arm shed slightly more people than the top one.
The dose with the biggest effect is therefore not automatically the dose a given person keeps taking. A course abandoned in month two returns nothing at any milligram, which is the practical argument for reading the side-effect record before committing to a long prepayment.
Three years in, the curve flattens unevenly
Treatment continued for the 1,032 participants who entered with prediabetes as well as obesity, to a total of 176 weeks. Mean change at that point was −12.3% at 5 mg, −18.7% at 10 mg and −19.7% at 15 mg, against −1.3% on placebo.[2]
Two things are visible in that row. The 15 mg figure barely moved across the extra two years, ending 1.2 points off its 72-week value, while the 5 mg figure gave back closer to three. And this is a subgroup, defined by prediabetes at entry, so it is not the same denominator as the headline. Over the same 176 weeks, type 2 diabetes was diagnosed in 1.3% on tirzepatide against 13.3% on placebo, a hazard ratio of 0.07.[2]
With type 2 diabetes the figures sit lower
SURMOUNT-2 ran 938 adults with a body-mass index of 27 or higher and glycated hemoglobin between 7% and 10% on 10 mg or 15 mg for the same 72 weeks. Least-squares mean change was −12.8% and −14.7% respectively, against −3.2% on placebo.[3]
Same molecule, same doses, same duration, and the top arm lands about six points below where it landed in people without diabetes. The pattern repeats across this drug class, and it is the same gap described for the other molecule in the semaglutide article. Anyone quoted a 21% figure at a diabetes intake is being quoted the wrong trial.
A lifestyle program first did not use up the effect
SURMOUNT-3 took a different starting line. It randomized 579 adults who had already achieved a reduction of 5% or more during a 12-week intensive lifestyle intervention, then gave them tirzepatide at the maximum tolerated dose or placebo for 72 weeks. Additional mean change from randomization was −18.4% on tirzepatide against +2.5% on placebo.[4]
The placebo arm is the informative half. People who had just succeeded on a structured program, and stayed on it, gained weight back over the following year. A further reduction of 5% or more was reached by 87.5% of the treated group against 16.5% of the others.[4]
That design also answers a question sellers tend to skip. Diet and activity had already produced a result in every participant before randomization, so the tirzepatide figure here is the effect layered on top of a program that had visibly worked. It is not a substitute for that program, and it did not run out of room because the program went first.
What maintenance looked like at 88 weeks
SURMOUNT-4 ran a 36-week open-label lead-in, during which participants lost a mean of 20.9%, and then randomized 670 of them to continue or to switch to placebo. By week 88, 89.5% of those who continued had held at least 80% of the weight lost during the lead-in, against 16.6% of those switched.[5] Measured across the whole 88 weeks, the two groups ended at −25.3% and −9.9%.
That is the figure to put beside an annual price rather than a monthly one, and it is the reason stopping deserves its own page. A plan whose cost climbs with the dose gets steadily worse as the months accumulate, which is what a flat per-dose price is worth paying attention to.
What none of these trials measured
Every figure above belongs to the branded, FDA-approved product at labeled doses, escalated under supervision, with diet and activity support running in both arms. The sellers listed on the review index overwhelmingly dispense compounded preparations, which are made against a prescription and are not reviewed by the FDA for safety, efficacy or quality before they reach anyone. A trial result describes the molecule and the schedule, not the vial that arrives in the mail.