- Generic name: Tirzepatide · Developer code: LY3298176 (Eli Lilly)
- CAS: 2023788-19-8
- Molecular weight: 4,813.5 g/mol
- Receptor targets: GLP-1R + GIPR (dual agonist)
- Peak Phase III weight loss: 20.9% at 72 weeks (15 mg/week, SURMOUNT-1)
- Approved therapeutics: Mounjaro (T2D, FDA 2022), Zepbound (obesity, FDA 2023)
- Research formats: Lyophilized vial (injectable), oral capsule
01 What Is Tirzepatide?
Tirzepatide (LY3298176) is a 39-amino acid synthetic peptide that functions as a dual agonist at both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptors. Developed by Eli Lilly, it represents the first approved dual incretin receptor agonist and the first approved pharmacotherapy to routinely produce greater than 20% mean body weight reduction in clinical trials.
The molecule uses a C20 fatty diacid moiety attached via a linker to enable albumin binding and extend half-life to approximately 5 days, enabling once-weekly subcutaneous dosing, similar to semaglutide. Tirzepatide was approved by the FDA for type 2 diabetes (Mounjaro) in May 2022 and for chronic weight management (Zepbound) in November 2023.
02 Dual GIP/GLP-1 Agonism Mechanism
Tirzepatide's GLP-1R agonism drives the same core effects as semaglutide: glucose-dependent insulin secretion, appetite suppression via central GLP-1R signalling, slowed gastric emptying, and glucagon suppression. What distinguishes tirzepatide is the additional GIPR co-agonism:
- Pancreatic GIPR: Synergistic enhancement of glucose-dependent insulin secretion
- Adipose GIPR: Modulation of lipid storage and mobilisation in adipose tissue
- Central GIPR: Hypothalamic appetite regulation and energy balance signalling
- Tolerability: GIP co-agonism may attenuate GLP-1-driven nausea, partly explaining tirzepatide's favourable GI tolerability profile
Crucially, the GIP and GLP-1 components appear to act synergistically rather than additively, the combined receptor engagement produces metabolic effects greater than would be predicted from either agonist alone, evidenced by tirzepatide's superior efficacy over matched-dose semaglutide despite similar GLP-1R affinity.
03 SURMOUNT Trial Programme (Obesity)
- 5 mg/week: −15.0% mean body weight (vs −3.1% placebo)
- 10 mg/week: −19.5% mean body weight
- 15 mg/week: −20.9% mean body weight
- ≥25% weight loss achieved by 36.2% of 15 mg participants
- Mean absolute weight loss: ~21 kg at 15 mg
SURMOUNT-2 (with T2D, 72 weeks) showed 12.8% and 14.7% reductions at 10 mg and 15 mg, lower than SURMOUNT-1, consistent with known attenuation of weight loss in the T2D population. SURMOUNT-3 and SURMOUNT-4 investigated maintenance of weight loss after lifestyle intervention run-in and treatment discontinuation, respectively, with SURMOUNT-4 demonstrating significant weight regain after stopping tirzepatide at 36 weeks.
SURMOUNT-5 provided the first head-to-head data against semaglutide 2.4 mg: tirzepatide 10 or 15 mg produced ~20% mean weight loss versus ~13.7% for semaglutide, a statistically significant 47% greater relative weight loss.
04 SURPASS Trial Programme (Type 2 Diabetes)
The SURPASS programme evaluated tirzepatide across 10 Phase III trials in T2D populations. Key results from SURPASS-2 (vs semaglutide 1 mg, 40 weeks, n=1,879):
- HbA1c reduction: −2.01% (5 mg), −2.24% (10 mg), −2.30% (15 mg) vs −1.86% semaglutide 1 mg
- Weight loss: −7.6 kg, −9.3 kg, −11.2 kg vs −5.7 kg for semaglutide
- Target HbA1c <7% achieved by 82–92% of tirzepatide patients vs 79% semaglutide
The SURPASS-CVOT cardiovascular outcomes trial (SURPASS-CVOT, n=13,000+) is ongoing. Interim data has not shown increased cardiovascular risk, and tirzepatide's predecessor semaglutide has demonstrated significant CV benefit in LEADER and SELECT trials.
05 Tirzepatide vs Semaglutide vs Retatrutide
| Parameter | Tirzepatide | Semaglutide 2.4 mg | Retatrutide |
|---|---|---|---|
| Receptor targets | GLP-1R + GIPR | GLP-1R only | GLP-1R + GIPR + GlucagonR |
| Peak weight loss (trials) | ~20.9% (72wk Ph III) | ~15% (68wk Ph III) | ~24.2% (48wk Ph II) |
| Approval status (2026) | Approved (T2D + obesity) | Approved (T2D + obesity) | Phase III ongoing |
| Thermogenic component | Modest (GIP) | No | Yes (glucagon) |
| Oral research format | Yes (capsule) | Rybelsus (oral semaglutide) | Capsule (investigational) |
06 Research Formats Available
Rainbow Peptide supplies tirzepatide in two research formats:
- Lyophilized vial (10mg): For injectable research protocols. Requires reconstitution with bacteriostatic water. Standard format for most in vivo and in vitro metabolic research studies.
- Oral capsule (10mg): For research protocols investigating oral GIP/GLP-1 agonism and oral bioavailability models. Note: the approved therapeutic tirzepatide is injectable, the oral capsule format is a research-only preparation.
Both formats are HPLC-verified at >98% purity with independent Certificate of Analysis. For Research Use Only.
07 Frequently Asked Questions
What is Tirzepatide?
Tirzepatide (LY3298176) is a synthetic dual agonist peptide that simultaneously activates GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptors. Developed by Eli Lilly, it is the active molecule in the approved medications Mounjaro (type 2 diabetes) and Zepbound (obesity). In research settings it is studied for metabolic syndrome, glycaemic regulation, cardiovascular risk, and hepatic steatosis models.
How much weight loss does Tirzepatide produce?
In the SURMOUNT-1 Phase III trial (72 weeks, n=2,539), tirzepatide produced mean body weight reductions of 15.0%, 19.5%, and 20.9% at the 5 mg, 10 mg, and 15 mg doses respectively, versus 3.1% for placebo. At 15 mg, 36.2% of participants achieved ≥25% weight loss. The SURMOUNT-2 trial in participants with T2D showed 12.8% and 14.7% reductions at 10 mg and 15 mg.
What is the difference between Tirzepatide and semaglutide?
Semaglutide (Wegovy) activates only GLP-1R. Tirzepatide adds GIPR co-agonism. The GIP component enhances insulin secretion, modulates adipose tissue lipid metabolism, and may reduce GLP-1-associated nausea, partly explaining tirzepatide's superior weight loss versus semaglutide despite both being weekly injections. In the SURMOUNT-5 head-to-head trial, tirzepatide 15 mg produced ~20% weight loss vs ~13.7% for semaglutide 2.4 mg.
How does Tirzepatide differ from Retatrutide?
Retatrutide adds a third target, glucagon receptor agonism, to the GLP-1/GIP dual agonism of tirzepatide. The glucagon component increases basal energy expenditure and promotes hepatic fat clearance. Phase II data for retatrutide showed ~24% mean weight loss at 48 weeks versus ~20% for tirzepatide 15 mg at 72 weeks in separate trials, though cross-trial comparisons require caution.
What is the mechanism of GIP receptor agonism in Tirzepatide?
GIPR (glucose-dependent insulinotropic polypeptide receptor) is expressed on pancreatic beta cells, adipocytes, bone cells, and central neurons. In the context of tirzepatide, GIPR agonism enhances glucose-dependent insulin secretion (synergistically with GLP-1R), modulates adipose lipid metabolism, and may have direct central effects on satiety and energy balance via hypothalamic GIPR signalling. The GIP component is also thought to partially attenuate GLP-1-driven nausea.
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