Tirzepatide versus semaglutide in everyday care: what a 511-patient study found

What the source reports

A retrospective multicentre study published online in Mayo Clinic Proceedings on 1 July 2026 compared medical records from adults who were prescribed weekly tirzepatide or semaglutide injections for obesity treatment in routine US healthcare. The records covered treatment between January 2021 and May 2024.

The cohort included 511 patients: 207 received tirzepatide and 304 received semaglutide. At 12 months, the study reported average total body weight loss of 16.6% with tirzepatide and 13.4% with semaglutide, a difference that was statistically significant.

The researchers also reported that 39.0% of tirzepatide users and 22.1% of semaglutide users reached at least 20% total body weight loss. Among patients without diabetes, average loss was 18.5% and 14.2%, respectively. These are group averages and thresholds, not predictions for an individual.

Who was represented in the records

The average starting body mass index was 40.0 kg/m² and the average age was 49.3 years. Women made up 74.8% of the cohort and 91.8% of participants were White.

The two treatment groups were not identical at the start. The tirzepatide group had a lower average body mass index than the semaglutide group, but a higher prevalence of type 2 diabetes and more previous use of another obesity medicine.

Those differences matter because diabetes status, starting weight, previous treatment and other clinical factors can influence weight change. Random allocation is designed to balance such factors; a retrospective record study cannot reproduce that protection completely.

The journal’s competing-interests statement says one coauthor has advised Novo Nordisk and another reported consulting, research and licensing relationships involving Novo Nordisk and several other organisations. Declared interests do not decide whether a result is valid, but they are relevant context when interpreting it.

Previous obesity treatment also appeared to matter

Patients with previous obesity-medicine use lost less weight on average than treatment-naive patients in both groups. For semaglutide, the reported averages were 10.4% with previous use and 14.4% without it. For tirzepatide, they were 16.1% and 17.1%.

The records do not establish one explanation for that pattern. People receiving another medicine previously may differ in treatment history, disease complexity, access, tolerance or earlier response in ways that an electronic record cannot fully capture.

This is one reason the study is useful as a description of clinical practice while remaining less definitive than a randomised comparison.

How to read the gastrointestinal side-effect figures

Gastrointestinal side effects were documented in 28.5% of tirzepatide users and 50.7% of semaglutide users in this cohort. The difference is noteworthy, but it does not prove that tirzepatide inherently causes fewer gastrointestinal effects.

A retrospective study depends on what patients report and what clinicians enter in the medical record. Follow-up frequency, dose, treatment duration, prescribing practices and reasons for switching or discontinuing can all affect which symptoms are captured.

The study evaluated recorded gastrointestinal symptoms rather than assigning treatments under a shared blinded protocol. Its safety figures therefore should not be treated as a universal side-effect rate or used alone to rank the medicines.

What ‘real world’ adds

Randomised trials answer whether an intervention can produce an outcome under a defined protocol. Real-world research asks what is associated with treatment when prescribing, dose progression, follow-up, coverage and adherence vary in ordinary healthcare.

That makes this study relevant to people whose experience does not resemble an ideal trial schedule. It included patients with and without diabetes and people who had previously used another obesity medicine.

Real-world does not mean more truthful than a trial; it answers a different question. Medical records can increase practical relevance while introducing confounding, missing information and inconsistent measurement.

How it fits with the randomised evidence

The direction of the finding is consistent with SURMOUNT-5, a separate 72-week randomised, open-label Phase 3b trial in 751 adults with obesity or overweight and a weight-related complication but without diabetes. That trial reported greater average weight reduction with tirzepatide than semaglutide.

SURMOUNT-5 used random assignment and a defined dose-escalation protocol, while the new study examined routine-care records that included patients with diabetes and previous obesity-medicine use. Their percentages should not be placed side by side as though they came from the same population or study design.

Agreement in direction across different designs strengthens the case that the association is worth attention, but the newer record study does not replace the randomised trial and does not determine which medicine is suitable for a particular person.

What remains uncertain

The study was retrospective, so treatment choice was influenced by real clinical and practical decisions rather than chance. Unmeasured differences between patients could account for some of the observed gap.

The cohort was drawn from several US centres but was predominantly White and female. More diverse populations and longer follow-up are needed before assuming the same averages apply across other communities, healthcare systems or treatment pathways.

Twelve months also cannot answer how durable the difference is, what happens after discontinuation or how the medicines compare for outcomes beyond weight. Documented gastrointestinal symptoms provide an incomplete view of tolerability and cannot establish comparative safety by themselves.

What this means for the individual

The difference between two group averages cannot predict one person’s result. Response may be affected by dose reached, time on treatment, adherence, diabetes status, other conditions, side effects and whether treatment can be continued.

Weight change is also only one part of a clinical decision. Contraindications, treatment goals, cardiovascular evidence, tolerability, access and the approved indication all require individual assessment with a qualified prescriber.

For someone already receiving treatment, the study is context for a clinical conversation rather than a reason to change medicine or dose. A personal record of medication, dose, symptoms and weight trend can help make that conversation more specific.

Bottom line

In this 511-patient routine-care cohort, tirzepatide was associated with greater average weight loss than semaglutide after 12 months. More tirzepatide users also reached the 20% weight-loss threshold.

The result is consistent in direction with randomised evidence, but the new analysis remains observational. It reports what happened in these medical records; it does not prove that one medicine will work better or be safer for every individual.