How it works
Tirzepatide binds two receptors rather than one. The GLP-1 arm does what semaglutide does: insulin release when glucose is high, glucagon suppression, slower gastric emptying, and appetite signalling in the hypothalamus.
The GIP arm is the less settled half. GIP receptor agonism appears to add to the weight effect and may improve tolerability at a given level of appetite suppression, but the mechanism is argued over more than the GLP-1 one is. What is not argued over is the size of the effect in trials.
What the evidence shows
Mean body weight fell about 15% on 5 mg, 19.5% on 10 mg and 20.9% on 15 mg, against roughly 3% on placebo. The largest average reduction reported for any approved agent in this class.
Mean reduction of roughly 13% on 10 mg and 15.7% on 15 mg. The pattern holds across the class: people with type 2 diabetes lose less on the same dose.
Greater reduction in both A1c and body weight at all three tirzepatide doses. Note the comparator was 1 mg, not the 2.4 mg used for weight management.
Participants switched to placebo regained substantially, the same pattern seen when semaglutide is stopped. Continued treatment maintained the loss.
Reduced the apnoea-hypopnoea index enough to support a separate indication in 2024.
The head-to-head result is narrower than it is usually quoted. SURPASS-2 compared tirzepatide against semaglutide 1 mg in people with type 2 diabetes, which is the diabetes dose, not the 2.4 mg weight-management dose. It is good evidence that tirzepatide is stronger. It is not a clean comparison of the two at their weight-management ceilings.
Typical dosing
The weight-management schedule. Increases come no sooner than four weeks apart, in 2.5 mg steps, and 5 mg, 10 mg and 15 mg are all recognised maintenance doses rather than waypoints.
Escalating faster than four-week intervals is the single most common cause of an avoidable bad first month.
Reported side effects
Rates are from SURMOUNT-1, which followed 2,539 adults for 72 weeks. Each range spans the three maintenance doses of 5 mg, 10 mg and 15 mg, because frequency rises with dose rather than being fixed. Most events were mild to moderate and concentrated during escalation rather than at maintenance. Between 4% and 7% of participants stopped because of adverse events depending on dose, against 2.6% on placebo. Check the current prescribing information for exact figures by individual dose.
Labelled warnings and contraindications
- Boxed warning for thyroid C-cell tumours, based on rodent studies. Human relevance is not established.
- Contraindicated with a personal or family history of medullary thyroid carcinoma, or with MEN2.
- Pancreatitis has been reported. Persistent severe abdominal pain needs assessment, not waiting.
- Gallbladder disease, including gallstones, occurs more often than on placebo.
- Dehydration from vomiting or diarrhoea can cause acute kidney injury.
- Retained stomach contents raise aspiration risk under general anaesthesia, so tell any surgical team you are on it.
- Tirzepatide can reduce the effectiveness of oral contraceptives. The labelled advice is a barrier method or a switch to non-oral contraception for four weeks after starting and after each dose increase. This one is specific to tirzepatide and is routinely missed.
- Hypoglycaemia risk rises when combined with insulin or a sulfonylurea, which usually means the other drug needs reducing.
- Not for use in pregnancy. Stopping is generally advised well ahead of trying to conceive.
Legal status and sourcing
Tirzepatide is FDA approved and available by prescription. It came off the FDA shortage list at the end of 2024, which removed most of the legal grounding for compounding copies of it. Compounded tirzepatide is therefore a narrower and more contested category than it was during 2023 and 2024.
The same two sourcing cautions apply as for semaglutide. Salt forms are not the approved active ingredient, and material sold for research use is not made, tested or labelled for people whatever the molecule on the label is.
What it costs
Compounded tirzepatide is not listed here because its availability and legal footing changed when the shortage was declared resolved. Prices verified to the date shown; check before relying on them.
How confident anyone can be
High for the effect size. Multiple large randomised trials, a head-to-head win against semaglutide at the diabetes dose, and a separate sleep apnoea indication built on its own trial.
Younger than semaglutide on hard outcomes. Semaglutide has the longer cardiovascular record and the longer post-marketing history. If your priority is the most established safety file rather than the largest average loss, that difference is the whole argument.
