Semaglutide vs tirzepatide: what's the difference?

The mechanical difference

Semaglutide is a GLP-1 receptor agonist. It mimics a gut hormone that signals fullness, slows how quickly the stomach empties, and reduces appetite. It is the active ingredient in Ozempic and Wegovy.

Tirzepatide does that too, and also acts on a second receptor, GIP. The working theory is that hitting both pathways produces a larger effect on appetite and metabolism than hitting one. It is the active ingredient in Mounjaro and Zepbound.

Both are weekly subcutaneous injections. Both are titrated upward slowly over months, because starting at a high dose reliably produces side effects that make people quit.

What the head-to-head trial found

The two have been compared directly in adults with obesity who did not have type 2 diabetes. Tirzepatide produced greater average weight loss than semaglutide over roughly 72 weeks — a difference of several percentage points of body weight, favouring tirzepatide.

Two things worth holding onto about that result. First, it is an average: some people lose a great deal on semaglutide and relatively little on tirzepatide, and there is currently no reliable way to predict which you will be before you try. Second, the trial studied the branded manufactured products, not compounded versions.

Side effects are broadly similar

For both, the common side effects are gastrointestinal: nausea, vomiting, diarrhoea, constipation. They are usually worst after a dose increase and often settle. They are also the most common reason people stop.

Both carry a warning about thyroid C-cell tumours based on rodent studies, and both are contraindicated if you have a personal or family history of medullary thyroid carcinoma or MEN 2. Pancreatitis and gallbladder problems are less common but documented for both.

This is not a complete list, and it is the part of the conversation worth having with a clinician who knows your history rather than reading off a page.

Cost, and why compounded is not the same thing

Tirzepatide generally costs more than semaglutide, and both branded products are expensive without insurance coverage.

Compounded versions are prepared by a licensed pharmacy from a prescription rather than manufactured by the brand-name maker. A compounded preparation is not an FDA-approved finished drug product, has not been through the approval process itself, and is not interchangeable with the branded product in a regulatory sense.

That distinction matters for what you can conclude from the trials. The evidence above is about the branded drugs. Compounded versions were not in those trials, so the results cannot simply be carried over.

What we genuinely do not know

We cannot predict who responds better to which. There is no test that tells you in advance, so in practice the answer is often found by trying one under supervision and reassessing.

Long-term data past a few years is still accumulating for both. What happens to weight after stopping is better understood — most people regain a substantial share — but the longer-term metabolic picture is less settled.

And we do not know how compounded preparations compare to branded ones in head-to-head terms, because that study has not been done.

How to actually decide

The useful inputs are your medical history, what you can tolerate, what you can afford to sustain, and — if you have coverage — what is actually available to you. Sustainability matters more than the trial average, because a drug you stop after two months does very little.

A clinician should be willing to tell you that neither is appropriate, if that is the honest read on your situation.