Truveta records show greater six-month weight loss with tirzepatide than semaglutide

Adults taking tirzepatide for obesity lost more weight over six months than adults taking semaglutide in routine US practice, according to a retrospective study of de-identified electronic health records from the Truveta database. Among 2,396 patients who stayed on treatment, tirzepatide was linked to an average 11.15% reduction in body weight versus 8.83% for semaglutide, an adjusted difference of 2.32 percentage points (95% CI: −3.17 to −1.48) ^[1].

The study included adults with obesity or overweight plus at least one obesity-related complication, and without diabetes, who started tirzepatide or semaglutide between December 2023 and June 2024 and adhered to treatment. Of the 2,396 patients analyzed, 1,003 took tirzepatide (sold as Mounjaro and Zepbound) and 1,393 took semaglutide (sold as Ozempic, Wegovy and Rybelsus) ^[1].

Higher proportions of patients on tirzepatide reached 5%, 10%, 15% and 20% weight-reduction targets, the study reports; the exact share of patients reaching each threshold has not been disclosed ^[1]. Tirzepatide was also associated with greater reductions in body mass index, blood pressure and hemoglobin A1c ^[1].

The dose patterns ran in the opposite direction from the results. More semaglutide patients were on higher doses — 67.7% received at least 1.7 mg — compared with tirzepatide patients, 42.4% of whom received at least 10 mg. The authors note that tirzepatide's comparative advantage appeared despite more semaglutide patients being at higher doses ^[1].

The primary analysis used propensity-score weighted regression, a method that adjusts for differences between the two groups, and sensitivity analyses including a modified intention-to-treat approach gave consistent findings ^[1]. The results line up with SURMOUNT-5, a randomized trial that found greater weight reduction with tirzepatide than semaglutide in adults with obesity without diabetes ^[1].

The study was funded by Eli Lilly and Company, which sells tirzepatide. Several authors are Eli Lilly employees or consultants at Analysis Group, which received funding from Lilly for the research; one author reports consulting fees and other payments from Novo Nordisk, which sells semaglutide, along with several other companies ^[1]. The underlying Truveta data are licensed and cannot be placed in public repositories ^[1].

Why it matters for patients

Most head-to-head information about these two drugs has come from randomized trials with strict eligibility rules. This study describes what happened in ordinary clinical records, which is closer to how the medications are actually prescribed. Still, it is an observational analysis, not a randomized trial, so it can show an association but cannot prove that tirzepatide itself caused the difference.

The averages describe groups, not individuals. A 2.32-percentage-point gap at six months says nothing about how any one person will respond, and the study reports only patients who adhered to treatment rather than everyone who started a prescription. Because the study excluded people with diabetes, the findings do not directly describe that group.

The study does not report side effects, discontinuation rates, cost or insurance coverage for either drug, so it does not answer questions about affordability or tolerability. It also does not report results beyond six months, so longer-term differences have not been established.

What happens next

No follow-up period beyond six months, and no further analyses of these records, have been announced ^[1].