Tirzepatide (LY3298176) is a peptide from Eli Lilly that activates two hormone receptors with one molecule: GIP and GLP-1. In the 72-week SURMOUNT-1 trial, adults with obesity on the highest dose lost on average 20.9% of their body weight. It became the first approved dual incretin agonist – for type 2 diabetes in 2022 and for weight management in 2023.[2]
Tirzepatide at a glance
- Type: dual agonist of the GIP and GLP-1 receptors, 39 amino acids, about 4813 g/mol.
- Developer: Eli Lilly; first human data published in 2018.[1]
- Half-life: about 5 days – given once weekly.[3]
- Best-known result: −20.9% mean body weight after 72 weeks at 15 mg.[2]
- Status: approved as a finished medicine for type 2 diabetes, weight management and sleep apnoea with obesity.
How does Tirzepatide work?
After a meal the gut releases the incretin hormones GIP and GLP-1. Both increase insulin secretion when blood sugar is high. GLP-1 also slows stomach emptying and acts on appetite centres in the brain, while GIP acts on fat tissue and may reduce the nausea that strong GLP-1 activation causes. Tirzepatide combines both signals: it is roughly as active as natural GIP at the GIP receptor and weaker than natural GLP-1 at the GLP-1 receptor.[1]
What is the structure of Tirzepatide?
The 39-amino-acid chain is based on the GIP sequence and contains two Aib units (α-aminoisobutyric acid) that protect it from the enzyme DPP-4. A C20 fatty diacid is attached to lysine 20 through a linker; it binds albumin in the blood and gives a half-life of about five days.[1][3] The molecular formula is C225H348N48O68 and the CAS number 2023788-19-2.
What did the clinical trials show?
In SURPASS-2, 1,879 adults with type 2 diabetes received Tirzepatide 5, 10 or 15 mg or Semaglutide 1 mg for 40 weeks. All three Tirzepatide doses lowered HbA1c and body weight more than Semaglutide.[4]
In SURMOUNT-1, 2,539 adults with obesity or overweight without diabetes were followed for 72 weeks. Mean weight change was −3.1% with placebo, −15.0% at 5 mg, −19.5% at 10 mg and −20.9% at 15 mg.[2]
| Weekly dose | Weight change after 72 weeks |
|---|---|
| Placebo | −3.1% |
| 5 mg | −15.0% |
| 10 mg | −19.5% |
| 15 mg | −20.9% |
SURMOUNT-4 looked at what happens after stopping: participants who switched to placebo after 36 weeks regained a large part of the lost weight, while those who continued kept losing.[5] SURMOUNT-OSA showed a marked fall in breathing interruptions during sleep in people with obesity and sleep apnoea.[6]
How does Tirzepatide compare with Semaglutide and Retatrutide?
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Receptors | GLP-1 | GIP + GLP-1 | GIP + GLP-1 + glucagon |
| Dosing in trials | Once weekly | Once weekly | Once weekly |
| Status | Approved | Approved | Phase 3 |
Tirzepatide is the only one of the three with a direct head-to-head obesity trial against Semaglutide: in SURMOUNT-5, average weight loss after 72 weeks was about 20% with Tirzepatide and about 14% with Semaglutide.[7] The triple agonist Retatrutide adds the glucagon receptor and is still in phase 3. For comparative laboratory research we stock Retatrutide 20 mg as well.
What doses were used in the trials?
All trials started at 2.5 mg once a week under the skin and raised the dose by 2.5 mg every four weeks until the assigned 5, 10 or 15 mg was reached. The slow escalation reduces gastrointestinal side effects.[2] For a 30 mg vial dissolved in 3 ml (10 mg/ml), 2.5 mg corresponds to 0.25 ml; our peptide calculator converts other volumes.
What side effects were reported?
The most common were gastrointestinal: nausea, diarrhoea, vomiting and constipation, mostly mild to moderate and during dose escalation. The approved products carry a warning about thyroid C-cell tumours seen in rodents, and pancreatitis and gallbladder problems are listed as rare risks.[2][4]
Why is Tirzepatide called a “twincretin”?
Because it acts on two incretin receptors at once – GIP and GLP-1. It is an informal nickname used in scientific commentary after the first trials.
How long does Tirzepatide stay in the body?
The half-life is about five days, and steady levels are reached after about four weekly doses.[3]
How should Tirzepatide be stored?
Keep the lyophilized powder dry and dark, long term at −20 °C. Once dissolved, store the solution at 2–8 °C and avoid repeated freezing and thawing. More in our guide How to store peptides.
For laboratory research we offer Tirzepatide 30 mg in stock.
Sources
- Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Molecular Metabolism. 2018;18:3–14. DOI ↗
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine. 2022;387(3):205–216. DOI ↗
- Urva S, et al. Population pharmacokinetics of the GIP/GLP receptor agonist tirzepatide. Clinical Pharmacokinetics. 2024. PubMed ↗
- Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. New England Journal of Medicine. 2021;385(6):503–515. DOI ↗
- Aronne LJ, Sattar N, Horn DB, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38–48. DOI ↗
- Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. New England Journal of Medicine. 2024;391(13):1193–1205. DOI ↗
- Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. New England Journal of Medicine. 2025. PubMed ↗
The information in this article is for educational purposes only and does not replace medical advice. Jolt Peptides products are intended solely for laboratory research, not for use in humans or animals.