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Semaglutide averaged 5.9% at a year in routine care, against 13.0% for tirzepatide

A 14,046-person cohort checked whether trial rankings survive contact with a pharmacy. The order held. The numbers shrank.

Neil Sanders6 min read
Mean weight change at 12 months, routine US caretirzepatide13%semaglutide5.9%the older three4%14,046 people. The trials report far larger numbers.

A buyer looking at a price is implicitly buying a result, and the result they have in mind comes from a trial. This cohort measured what the same drugs did in routine American care, and the semaglutide number is the one worth sitting with: -5.9% at twelve months [1]. That is the gap this desk keeps flagging between what a page promises and what a year delivers, as in the cost per patient who actually hits target.

Across 14,046 adults with a BMI of 30 or more, mean twelve-month weight change was -13.0% on tirzepatide, -5.9% on semaglutide, and roughly -4.0% each on exenatide, dulaglutide and liraglutide. Against liraglutide as the reference, the adjusted hazard for reaching at least 15% weight loss was 5.57 for tirzepatide and 1.77 for semaglutide.

This desk will not tell you why the gap exists, because this study does not say. Adherence, the dose people actually reach, who stays in the records long enough to be measured at twelve months, and the supply shortages that ran through this period all plausibly contribute, and none of them is separated out here. What can be said is that the gap is large and that the adherence evidence points the same way, as in the fill and discontinuation rates.

One asymmetry is worth recording. Weight loss was greater in people without type 2 diabetes for semaglutide, but similar with and without diabetes for tirzepatide. So the diabetes status that changes what you are prescribed and what a plan will cover also changes what you should expect — unevenly, by molecule. That interacts directly with the coverage rules in what insurance actually covers.

For anyone comparing self-pay prices, the practical adjustment is straightforward. Take the monthly price, and pair it with the routine-care result rather than the trial result. On those terms the tirzepatide-to-semaglutide price gap has to be judged against a 13.0%-to-5.9% result gap, not against the closer figures the trials report — which is a different comparison from the one in the headline versus billed price, and a more consequential one.

Frequently asked

Why is the semaglutide figure so much lower than the trials?
This study does not say. Adherence, the dose people reach, who remains in the records at twelve months and shortage-era supply are all plausible contributors, and none is separated out here.
Did the trial ranking hold up in practice?
Yes. Tirzepatide came first, semaglutide second, and exenatide, dulaglutide and liraglutide clustered together behind at roughly -4.0%.
Does diabetes status change what to expect?
For semaglutide, weight loss was greater in people without type 2 diabetes. For tirzepatide, results were similar with and without it.

Sources

  1. [1] Hwang I, Lee SW, Kim Y (2026). Real-World Comparative Weight Loss of GLP-1 Receptor Agonists in the All of Us Research Program: A Retrospective Cohort Study Drug Design, Development and Therapy. PMID 42518911

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