Semaglutide vs Tirzepatide

The head-to-head has actually been run

Most comparisons on this site end in “no one has tested it.” Not this one. SURMOUNT-5 put them against each other directly and tirzepatide won, roughly 20% body weight lost against 14%. The mechanistic difference is that tirzepatide agonises GIP as well as GLP-1, and that second receptor appears to be what buys the extra effect. Semaglutide has the longer safety record and the cardiovascular outcome data from SELECT; tirzepatide is newer with a shorter track record. Both are approved, both carry the same thyroid C-cell warning, and both see most of the weight return if you stop.

Pancreatic beta cell close-up showing a nucleus and many small secretory granules by a capillary.

Semaglutide Metabolic Ozempic, Wegovy, Rybelsus Full entry →

Two endocrine pancreatic cells with distinct subtle coral and navy vesicles next to a tiny capillary.

Tirzepatide Metabolic Mounjaro, Zepbound Full entry →

Semaglutide compared with Tirzepatide
	Semaglutide	Tirzepatide
Evidence behind it	Human trials	Human trials
Worth knowing	Nausea, vomiting and constipation are common, and a minority stop because of them. Weight returns when it is stopped — STEP 4 showed most of it back within a year. It carries a boxed warning for thyroid C-cell tumours seen in rodents, and gastroparesis and pancreatitis have been reported. Lean mass loss is real and argues for resistance training alongside it.	The same gastrointestinal profile as semaglutide and the same boxed warning for thyroid C-cell tumours. Weight returns on stopping — SURMOUNT-4 showed substantial regain after withdrawal. Being newer, its long-term safety record is shorter than semaglutide's.
Approval	Approved · US, EU & worldwide	Approved · US & EU
Category	Metabolic	Metabolic
What it is	The compound that made this whole class famous. A 31-amino-acid rewrite of the gut hormone GLP-1, with one unnatural amino acid to stop enzymes cutting it and a fatty diacid chain to bind albumin — together taking its half-life from two minutes to about a week.	A 39-amino-acid peptide that hits two gut hormone receptors at once — GIP as well as GLP-1. That second target is what appears to separate it: in head-to-head trials it outperforms semaglutide on weight.
How it works	Activates GLP-1 receptors in the pancreas, stomach and brain: more insulin when glucose is high, less glucagon, slower gastric emptying, and reduced appetite signalling in the hypothalamus and hindbrain.	A dual agonist at both the GIP and GLP-1 receptors. GLP-1 activation does what it does for semaglutide; adding GIP appears to improve insulin sensitivity and may blunt some of the nausea, though exactly why the combination works better is not settled.
What studies report	Around 15% mean body weight loss at 2.4 mg weekly over 68 weeks in STEP 1, against 2.4% on placebo 20% reduction in major cardiovascular events in SELECT, in people with obesity and heart disease but not diabetes Consistent HbA1c reduction across the SUSTAIN diabetes programme Roughly a third of the weight lost is lean mass, as with most rapid weight loss	Around 21% mean body weight loss at 15 mg weekly over 72 weeks in SURMOUNT-1 Beat semaglutide head-to-head in SURMOUNT-5, roughly 20% against 14% Superior HbA1c reduction to semaglutide 1 mg in SURPASS-2 Approved for obstructive sleep apnoea in obesity on the back of the SURMOUNT-OSA trials
Dosing	From studies 2.4 mg weekly, subcutaneous — STEP 1, obesity (n=1,961). −14.9% body weight vs −2.4% placebo 2.4 mg weekly, subcutaneous — SELECT cardiovascular outcomes (n=17,604). 20% fewer major cardiovascular events 1.0 mg weekly, subcutaneous — SUSTAIN programme, type 2 diabetes. HbA1c reduction of roughly 1.5 points Reported, not evidence Titrated up over 16+ weeks — 0.25 mg, then 0.5, 1.0, 1.7, 2.4 — to limit nausea Widely obtained through compounding pharmacies and grey-market suppliers at lower cost Some people stay at a lower maintenance dose once weight stabilises	From studies 15 mg weekly, subcutaneous — SURMOUNT-1, obesity (n=2,539). −20.9% body weight vs −3.1% placebo 10–15 mg weekly, subcutaneous — SURMOUNT-5, head-to-head against semaglutide 2.4 mg. ≈20% vs ≈14% weight loss 5–15 mg weekly, subcutaneous — SURPASS-2, type 2 diabetes. Greater HbA1c reduction than semaglutide 1 mg Reported, not evidence Titrated from 2.5 mg upward in 2.5 mg steps every four weeks Many stop climbing once an effective dose is reached rather than going to 15 mg
Why people take it	Weight lossType 2 diabetesAppetite and food-noise reductionCardiovascular risk reduction	Weight lossType 2 diabetesObstructive sleep apnoeaAppetite reduction
In practice	Vastly more used than anything else in this library, almost all of it through prescription Compounded and research-chemical versions circulate widely, with no guarantee of identity or purity Stopping generally means regaining most of the weight, which is why it is framed as ongoing treatment	Increasingly the first choice over semaglutide where cost and supply allow Same compounded and grey-market availability problem as semaglutide
Route	Subcutaneous injection, weekly; also an oral tablet (Rybelsus)	Subcutaneous injection, weekly

Rows describing reported use say what people do, not what has been shown to work. Evidence strength is graded the same way across the whole library, so the two columns are directly comparable.

Read the full entries

Semaglutide → Tirzepatide → Open this in the compare tool →

Other comparisons

Educational information only. Nothing here is medical advice, a dosing protocol, or a recommendation to use any compound. Comparing two compounds is not a suggestion to take either one. Talk to a licensed clinician before acting on anything you read here. How to read these entries.