Large US study finds tirzepatide beat semaglutide on one-year weight loss after bariatric surgery

A retrospective study of 208,155 people across the United States who had metabolic and bariatric surgery found that those still taking tirzepatide a year afterward had lost 17.2 percent of their body weight, while those on semaglutide had lost 12.0 percent ^[1][2].

The work was published in eClinicalMedicine and drew on de-identified electronic health records from 43,104 academic and private medical centers nationwide, covering the years 2018 through 2025 ^[1][2]. Of the 208,155 patients who had surgery, 39,750 were prescribed an incretin-based drug afterward — either semaglutide (marketed as Ozempic, Wegovy and Rybelsus) or tirzepatide (marketed as Mounjaro and Zepbound) ^[2].

Researchers used propensity score matching to compare the two molecules by dose, by how soon after surgery treatment began, and by the type of operation performed ^[1][2].

The weight-loss gap

Among patients who remained on treatment for a full year, tirzepatide's 17.2 percent total weight loss against semaglutide's 12.0 percent amounted to an adjusted difference of 5.16 percentage points (95% CI 4.17-6.16, p < 0.001) ^[2]. The report describes the weight loss as dose-dependent for both drugs, meaning higher prescribed doses tracked with greater loss ^[2].

When treatment started also tracked with results. Patients whose first prescription came 53 to 79 months after their operation lost 15.4 percent of body weight over the year, compared with 13.5 percent for those who started 12 to 24 months after surgery (p < 0.001) ^[2].

The heart-risk finding

For cardiovascular outcomes, the researchers paired each incretin user with a similar patient who did not take one of these drugs, then ran inverse probability of censoring-weighted Cox models ^[2]. Pooled incretin therapy showed no association with major adverse cardiovascular events — a composite of non-fatal heart attack, non-fatal stroke or cardiovascular death — with a hazard ratio of 0.91 (95% CI 0.80-1.05, p = 0.19) ^[2].

That analysis covered 35,651 users and 35,651 matched non-users, with 884 MACE events recorded: 377 among users and 507 among non-users ^[2]. Because the confidence interval crosses 1.0, the result is a neutral finding rather than evidence that the drugs protect the heart ^[2].

Limits of the evidence

This is an observational cohort, not a randomized trial, so it can show associations but not that either drug caused the difference in weight loss ^[2]. The authors write that prospective studies are needed to establish causality, to gauge how long the weight-loss benefit lasts, and to determine whether these therapies add cardiovascular protection in people who have had bariatric surgery ^[2]. Results cover the first year only; outcomes beyond that point have not been reported ^[2]. The published findings also do not disclose how many patients had type 2 diabetes or the specific doses individual patients reached ^[2].

The research received no specific funding. One author reports serving on an advisory board and a speakers bureau for Eli Lilly, which markets tirzepatide, and on an advisory board for Boehringer Ingelheim; other authors report ties to Medtronic, Ethicon, Intuitive Surgical and UBS ^[2].

Why it matters for patients

Weight regain after bariatric surgery is common, and the study describes long-term weight management after these operations as a persistent clinical challenge ^[2]. That is the context for testing whether GLP-1 and dual GIP/GLP-1 drugs help people who have already had surgery, and this analysis compares the two main molecules used that way in a very large US records sample.

Three details shape how the numbers should be read. First, the 17.2 percent and 12.0 percent figures describe only patients who stayed on therapy for a year, so they say nothing about people who stopped early ^[2]. Second, the cardiovascular result is neither harm nor benefit — the interval spans 1.0, and the authors say added heart protection after bariatric surgery is not yet established ^[2]. Third, the study does not identify which drug suits a particular patient, and it does not test what happens when someone switches from one to the other ^[2].

Nothing in the findings changes what a given patient and their clinician weigh when choosing treatment, and the analysis does not compare these drugs with other options after surgery ^[2].

What happens next

The authors call for prospective research on cause and effect, on whether weight loss holds up over longer periods, and on any additive cardiovascular effect in the post-surgery population ^[2]. No follow-up trial, completion date or regulatory action has been announced ^[2].