Tirzepatide
Tirz · Mounjaro · Zepbound · LY3298176
Weekly dual GIP/GLP-1 agonist; beats semaglutide on total weight loss in head-to-head data.
Typical dose
5 mg
Once weekly
Range
2.5–15
mg
Half-life
4.9 days
see Dosing
Evidence
Human trials
Subcutaneous
What it is
Tirzepatide is a 39-amino-acid synthetic peptide built on the GIP backbone that activates both the GIP and GLP-1 receptors from a single molecule. A C20 fatty diacid chain binds albumin and stretches its half-life to about five days, giving once-weekly dosing.
It is approved as Mounjaro for type 2 diabetes and Zepbound for weight management. In SURMOUNT-1, 15 mg weekly produced roughly 21% mean body weight loss over 72 weeks, and in the SURPASS-2 head-to-head against 1 mg semaglutide it won on both HbA1c and weight.
The GIP component is the practical difference from semaglutide. Adding GIP agonism appears to improve nausea tolerance at equivalent appetite suppression and adds effects on adipose tissue handling that pure GLP-1 agonists do not have.
It has become the default choice for people who want maximum appetite suppression from an approved compound. Grey-market vials are sold in 10-60 mg sizes and are the same molecule when legitimate, but batch verification matters.
How it works
Tirzepatide hits two incretin receptors at once. GLP-1 receptor activation drives the familiar effects: central satiety signalling, slowed gastric emptying, glucose-dependent insulin release and glucagon suppression. GIP receptor activation adds a second appetite-suppressing signal through a partly separate central pathway and improves how adipose tissue takes up and stores nutrients, which appears to make the insulin-sensitising effect stronger than GLP-1 agonism alone.
The two signals are not simply additive on side effects. Co-agonism seems to blunt some of the nausea that comes with equivalent GLP-1 exposure, which is why tirzepatide can be pushed to a higher effective appetite suppression than semaglutide before GI tolerance becomes the limiting factor.
Dosing
Start at 2.5 mg regardless of your semaglutide history; the two are not dose-equivalent. Escalate in 2.5 mg steps no faster than every 4 weeks, to a label ceiling of 15 mg weekly.
Standard titration
| Step | Dose | Note |
|---|---|---|
| Weeks 1-4 | 2.5 mg | Tolerance-building dose; not intended as a therapeutic dose |
| Weeks 5-8 | 5 mg | First full maintenance dose; many people never need more |
| Weeks 9-12 | 7.5 mg | Step up only if appetite control has faded |
| Weeks 13-16 | 10 mg | Common upper working dose |
| Weeks 17-20 | 12.5 mg | Diminishing returns start here for most people |
| Week 21 onward | 15 mg | Label maximum; GI side effects and lean mass loss scale with dose |
Reconstitution calculator
Pre-loaded with Tirzepatide’s vial size, water volume and typical dose. Change anything.
Typical: 5 mg · range 2.5–15
Draw to
50 u
0.5 mL · 5 mg
Concentration
10 mg/mL
100 mcg per unit
Doses per vial
2
Vial lasts
2 weeks
CheckThe draw fills more than 90% of the barrel. Workable, but there is no room for an air bubble or a correction.
Once mixed
Refrigerate at 2-8C and use within about 4-6 weeks; discard if it goes cloudy or shows visible particles.
A 10 mg vial with 1 mL bacteriostatic water gives 10 mg/mL, so 2.5 mg is 25 units on a U-100 insulin syringe, 5 mg is 50 units and 10 mg is a full 100 units. Some people use 2 mL for an easier-to-measure 5 mg/mL, which is fine at low doses but needs more than one syringe above 5 mg. Add water down the vial wall and swirl gently; never shake.
Storage
Before mixing
Refrigerated at 2-8C the sealed powder is stable for years; it survives shipping at ambient temperature, but keep it dark and dry.
After mixing
Refrigerate at 2-8C and use within about 4-6 weeks; discard if it goes cloudy or shows visible particles.
Reported benefits
- ▪Roughly 21% mean body weight loss at 15 mg over 72 weeks in trial conditions
- ▪Beat 1 mg semaglutide on both weight and HbA1c in a direct head-to-head trial
- ▪Appetite suppression is often described as cleaner than semaglutide at equal effect
- ▪Strong glycaemic control with low hypoglycaemia risk as a single agent
- ▪Once-weekly dosing with stable plasma levels
- ▪Improves blood pressure, triglycerides and hepatic fat
Side effects
- ▪Nausea, vomiting, diarrhoea and constipation, concentrated in the days after a dose increase
- ▪Reflux, sulphurous burps and early fullness from delayed gastric emptying
- ▪Lean mass loss, which is proportionally similar to semaglutide and scales with how fast you drop weight
- ▪Injection site reactions, usually mild and transient
- ▪Gallstones, associated with rapid weight loss
- ▪Acute pancreatitis, uncommon but reported
- ▪Hair shedding several months in, driven by the deficit rather than the drug
- ▪Markedly delayed gastric emptying — the stomach can still hold solid food many hours after a meal, so any surgery, endoscopy or procedural sedation needs the drug held beforehand and the anaesthetist told, because of the aspiration risk from retained gastric contents.
Do not use if
- ▪Personal or family history of medullary thyroid carcinoma or MEN2 syndrome
- ▪History of pancreatitis
- ▪Gastroparesis or other significant gastric motility disorder
- ▪Pregnancy or trying to conceive; oral contraceptive absorption can also be reduced during titration
- ▪Severe pre-existing GI disease
Evidence level — Human trials
Controlled human clinical data exists.
FDA- and EMA-approved as a prescription drug (Mounjaro, Zepbound); lyophilised vials sold outside that channel are unlicensed research-chemical supply.
Commonly run with
Cagrilintide
Long-acting amylin analogue run weekly for satiety, usually alongside a GLP-1.
2.4 mg · once weekly
BPC-157
Gastric-juice-derived pentadecapeptide studied for tendon, ligament and gut healing.
250 mcg · 1x daily (some split into 2x daily during an acute injury)
Tesamorelin
The only FDA-approved GHRH analogue, proven to shrink visceral abdominal fat.
2 mg · once daily
HGH
Recombinant human growth hormone, the reference compound every GH peptide tries to imitate.
2 IU · Once daily, split into two injections above about 4 IU
5-Amino-1MQ
Oral NNMT inhibitor aimed at fat-cell metabolism and NAD+ salvage. Mouse data only.
100 mg · once daily
Tirzepatide FAQ
How does 5 mg tirzepatide compare to 1 mg semaglutide?+
There is no clean conversion, because the receptor profiles differ. SURPASS-2 found 5 mg tirzepatide outperformed 1 mg semaglutide on weight and HbA1c, so treat 5 mg as roughly comparable or slightly stronger. Regardless of what you were on before, restart at 2.5 mg.
Do I have to go all the way to 15 mg?+
No. The dose that controls your appetite is your dose. Plenty of people hold at 5 or 7.5 mg for the whole cut, and side effects and lean mass loss both scale with dose. Only step up when appetite control has genuinely faded.
Can I run it alongside a steroid cycle or TRT?+
There is no direct interaction. The real issue is that heavy appetite suppression makes it hard to eat enough protein and total calories to hold muscle, so it works against a bulk. On a cut it pairs fine, provided protein stays high and you do not drop training volume.
How do I handle the constipation?+
It is the most common long-term complaint and mostly comes from low food volume, low fibre and low fluid intake once you are eating far less. Fibre, adequate water and magnesium handle it for most people. Persistent severe constipation or vomiting is a reason to drop a dose step, not to push on.
What is a reasonable rate of weight loss?+
Around 0.5-1% of body weight per week is where lean mass retention still works. Faster than that and you are trading muscle and gallbladder health for scale movement. If you are dropping faster, eat more rather than raising the dose.
References
- 1.Tirzepatide Once Weekly for the Treatment of Obesity — New England Journal of Medicine (2022) PMID 35658024
- 2.Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes — New England Journal of Medicine (2021) PMID 34170647
- 3.A phase 1 multiple-ascending dose study of tirzepatide in Japanese participants with type 2 diabetes — Diabetes, Obesity and Metabolism (2022) PMID 34647404
More fat loss & metabolic
5-Amino-1MQ
Oral NNMT inhibitor aimed at fat-cell metabolism and NAD+ salvage. Mouse data only.
100 mg · once daily
AOD-9604
Modified hGH tail fragment sold for lipolysis without the IGF-1 rise of growth hormone.
300 mcg · once daily
Cagrilintide
Long-acting amylin analogue run weekly for satiety, usually alongside a GLP-1.
2.4 mg · once weekly
HGH Fragment 176-191
The C-terminal tail of growth hormone, sold for fat loss on almost entirely rodent evidence.
250 mcg · Once daily, fasted (many split it into two 250 mcg doses)