For laboratory research only. Not for human or animal use. This article gives no dosing, administration or therapeutic advice.
Short answer: semaglutide, tirzepatide and retatrutide are three long-acting peptides that differ mainly in how many hormone receptors they activate. Semaglutide is a GLP-1 receptor agonist,[1] tirzepatide acts on the GLP-1 and GIP receptors,[2][3] and retatrutide acts on the GLP-1, GIP and glucagon receptors.[4] Their regulatory positions differ just as much: semaglutide and tirzepatide are FDA-approved prescription drugs, while retatrutide remains an investigational drug in phase 3 trials.[5][6] This article compares their design and the published study record. It makes no efficacy or treatment claims and gives no doses.
One receptor, two receptors, three receptors
All three molecules start from the incretin idea: gut hormones such as GLP-1 and GIP act on G protein-coupled receptors that regulate insulin secretion and appetite signaling. Native GLP-1 is cleared within minutes, so each drug program engineered its peptide for stability.
Semaglutide keeps the GLP-1 backbone with two substitutions (Aib at position 8, Arg at 34) and a fatty-acid derivative on lysine 26. In its discovery paper, the albumin affinity rose while GLP-1 receptor affinity fell about three-fold compared with liraglutide, and plasma half-life in mini-pigs was 46.1 hours.[1] Cryo-EM structures show semaglutide engaging the GLP-1 receptor much like native GLP-1, with differences in receptor motion.[7]
Tirzepatide is a fatty-acid-modified peptide built to activate both incretin receptors.[2] In cell assays it matched native GIP at the GIP receptor but was biased at the GLP-1 receptor, favoring cAMP over beta-arrestin recruitment, which its authors call “imbalanced” toward GIP.[3] Cryo-EM work attributed this profile to both the amino acid sequence and the fatty-acid modification.[8] In obese mice, GIP receptor agonism contributed to insulin sensitization independent of weight change.[9]
Retatrutide (LY3437943) adds the glucagon receptor. In vitro, its activity was balanced at the glucagon and GLP-1 receptors with more activity at the GIP receptor; in obese mice, the glucagon-receptor component was linked to higher energy expenditure on top of reduced food intake.[4]
Identity at a glance
| Field | Semaglutide | Tirzepatide | Retatrutide |
|---|---|---|---|
| PubChem CID | 56843331 | 166567236 | 171390338 |
| Molecular formula | C187H291N45O59 | C225H348N48O68 | C221H342N46O68 |
| Molecular weight | 4114 g/mol | 4813 g/mol | 4731 g/mol |
| CAS number | 910463-68-2 | 2023788-19-2 | 2381089-83-2 |
| Receptors | GLP-1R | GLP-1R, GIPR | GLP-1R, GIPR, GCGR |
| Fatty-acid chain (PubChem name) | C18 diacid (octadecanoic) | C20 diacid (icosanoic) | C20 diacid |
| Reported half-life in humans | About 1 week[10] | About 5 days[11] | About 6 days[12] |
| Developer | Novo Nordisk | Eli Lilly | Eli Lilly |
Formulas and weights are PubChem’s computed values. The retatrutide CID above is the one printed on Purity’s Horizon Analytical retatrutide reports, which list the same formula. Half-life figures are pharmacokinetic descriptions from the cited studies, not usage guidance.
Regulatory status, stated neutrally
- Semaglutide: FDA-approved prescription drug. Ozempic received its original FDA approval on December 5, 2017 (Drugs@FDA, NDA 209637), and Wegovy on June 4, 2021 (NDA 215256). A 2018 drug profile describes the first approval.[13]
- Tirzepatide: FDA-approved prescription drug. Mounjaro was approved on May 13, 2022 (NDA 215866), and Zepbound on November 8, 2023 (FDA press release).[14]
- Retatrutide: investigational. Phase 3 reports appeared in 2026,[5][6][15] but as of October 1, 2026 it has no FDA approval.
The study record, described neutrally
The table lists design, population and primary endpoint for representative studies. “Reported” restates the authors’ conclusion on the primary endpoint without effect sizes; the PMID links lead to the full abstracts.
| Study | Design / model | Population | Primary endpoint | Reported | Ref |
|---|---|---|---|---|---|
| Retatrutide discovery | Cell assays, obese mice, phase 1 | Mice; phase 1 participants | Receptor activity; safety | Triple agonism confirmed; profile similar to other incretins | [4] |
| Phase 1b | Randomized, placebo-controlled, multiple ascending dose | Type 2 diabetes | Safety and pharmacokinetics | Acceptable safety; half-life about 6 days | [12] |
| Retatrutide phase 2 | Randomized, placebo-controlled, 48 weeks | Adults with obesity | Body-weight change | Met; dose-related GI events and heart-rate increases | [16] |
| Retatrutide phase 2 (T2D) | Placebo- and dulaglutide-controlled | Type 2 diabetes, USA | HbA1c change | Met | [17] |
| TRIUMPH-1 | Phase 3, randomized, 80 weeks | Obesity without diabetes | Body-weight change; knee pain and sleep-apnea subgroups | Met; GI events most common | [5] |
| TRIUMPH-2 | Phase 3, placebo-controlled | Obesity with type 2 diabetes | Body-weight change | Met | [6] |
| SURPASS-2 | Phase 3, open-label, active comparator | Type 2 diabetes | HbA1c, tirzepatide vs semaglutide | Noninferior and superior; more serious AEs with tirzepatide | [18] |
| SURMOUNT-1 | Phase 3, placebo-controlled, 72 weeks | Obesity without diabetes | Body-weight change | Met; GI events most common | [19] |
| STEP 1 | Phase 3, placebo-controlled | Overweight or obesity | Body-weight change | Met; more GI-related discontinuations | [20] |
| SUSTAIN-6 | Cardiovascular outcomes trial | Type 2 diabetes, high CV risk | Major adverse CV events | Noninferiority confirmed; more retinopathy complications | [21] |
| evoke / evoke+ | Phase 3, oral semaglutide | Early Alzheimer’s disease | Clinical progression | Not met | [22] |
| Three-drug kidney study | Mouse fibrosis and aging models | Mice | Renal fibrosis markers | Drug- and model-specific pathway effects | [23] |
Two patterns stand out. Gastrointestinal adverse events dominate the safety sections of all three programs, and retatrutide’s phase 2 trial reported dose-dependent heart-rate increases that peaked at 24 weeks.[16] The evoke program is a reminder that these drugs do not succeed in every indication tested.[22]
What the evidence does not show
- No human head-to-head trial of retatrutide. Retatrutide has not been compared directly with tirzepatide or semaglutide in a published human trial; only tirzepatide vs semaglutide has phase 3 head-to-head data.[18]
- More receptors is not automatically better. Each added receptor brings its own biology, including glucagon-receptor effects on energy expenditure in mice and heart-rate changes in people.[4][16]
- Mouse comparisons do not rank drugs for people. The three-drug kidney study generated hypotheses at the doses tested in mice, by its own description.[23]
- Trial results describe trial products. Phase 3 data apply to the sponsor’s formulated drug under trial conditions, not to research reagents.
- Long-term data for retatrutide are still accumulating. Its phase 3 program reported only in 2026.[5][15]
Purity catalog records and how to read their COAs
Purity lists retatrutide as 10mg, 15mg, 20mg and 30mg vials plus a pen, and tirzepatide (Tirz-Luxe) as 10mg, 15mg, 20mg and 30 mg vials plus a pen. Purity sells no semaglutide. As read from the posted PDFs on October 1, 2026:
| Listing | Lot (Horizon Analytical, UPLC/MS) | Measured vs label | Purity | Endotoxin |
|---|---|---|---|---|
| Retatrutide 10mg (pen links the same lot) | PCCL-5859103-P, analyzed 06/11/2026 | 9.97 mg / 10mg | 99.34% | <0.05 EU/mL |
| Retatrutide 10mg, earlier lot (superseded; its PDFs were removed from the product page on October 1, 2026) | PCCL-6141790, analyzed 04/05/2026 | 9.97 mg / 10mg | 99.39% | 0.061 EU/mL |
| Retatrutide 15mg | PCCL-5244055-P, 06/11/2026 | 14.76 mg / 15mg | 99.39% | <0.05 EU/mL |
| Retatrutide 30mg | PCCL-1857910-P, 05/04/2026 | 29.75 mg / 30mg | 99.42% | <0.05 EU/mL |
| Retatrutide 20mg | A batch COA for this product isn’t posted yet. | |||
| Tirz-Luxe 10mg (pen links the same lot) | PCCL-2576448-P, 05/04/2026 | 10.1 mg / 10mg | 99.35% | <0.05 EU/mL |
| Tirz-Luxe 30 mg | PCCL-6878731-P, 06/11/2026 | 30.25 mg / 30mg | 99.29% | <0.05 EU/mL |
| Tirz-Luxe 15mg and 20mg | A batch COA for these products isn’t posted yet. | |||
When you read one of these reports, check four things. The lot on the report should match the lot you receive; the retatrutide 10mg page links two lots, so the match matters. The compound line should name the right molecule: retatrutide and tirzepatide differ by about 82 g/mol, which mass spectrometry resolves easily. The measured quantity is reported against the label spec, so a 15mg result tells you nothing about a 20mg vial. And the endotoxin report is a separate document with its own lot suffix. For background, see What is retatrutide?, browse every report in the COA library, or start from the page for how to buy research peptides online in the USA.
Frequently asked questions
Is retatrutide FDA-approved?
No. As of October 1, 2026, retatrutide is an investigational drug in phase 3 clinical trials and has no FDA approval for any use. Semaglutide and tirzepatide are FDA-approved prescription drugs sold under brand names such as Ozempic, Wegovy, Mounjaro and Zepbound.
What is the main structural difference between the three peptides?
Receptor reach. Semaglutide is a GLP-1 analog that acts on the GLP-1 receptor. Tirzepatide adds activity at the GIP receptor. Retatrutide adds a third target, the glucagon receptor. All three carry a fatty-acid side chain that binds albumin and extends half-life.
Have the three been compared head to head?
Partly. A phase 3 trial compared tirzepatide with semaglutide in type 2 diabetes (SURPASS-2). We found no published head-to-head human trial of retatrutide against either drug; a 2026 mouse study compared all three in kidney fibrosis models.
Does Purity sell semaglutide?
No. Purity Collective lists retatrutide and tirzepatide research materials only. Semaglutide is described in this article from the published literature for comparison.
Is a research-grade tirzepatide vial the same as Mounjaro or Zepbound?
No. Mounjaro and Zepbound are FDA-approved drug products with a specific manufacturer, formulation and label. A research-grade vial is a laboratory reagent sold for in vitro and preclinical research only, and its quality is documented by its own batch COA.
Which Purity retatrutide and tirzepatide listings have a batch COA?
As of October 1, 2026, posted Horizon Analytical reports cover retatrutide 10mg (also linked from the pen), 15mg and 30mg, and Tirz-Luxe 10mg (also linked from the tirzepatide pen) and 30mg. A batch COA for retatrutide 20mg, Tirz-Luxe 15mg or Tirz-Luxe 20mg isn’t posted yet.
References
- Lau J, Bloch P, Schäffer L et al. (2015). Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. PMID: 26308095. doi: 10.1021/acs.jmedchem.5b00726.
- Coskun T, Sloop KW, Loghin C et al. (2018). 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. Mol Metab. PMID: 30473097. doi: 10.1016/j.molmet.2018.09.009.
- Willard FS, Douros JD, Gabe MB et al. (2020). Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. PMID: 32730231. doi: 10.1172/jci.insight.140532.
- Coskun T, Urva S, Roell WC et al. (2022). LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. PMID: 35985340. doi: 10.1016/j.cmet.2022.07.013.
- Jastreboff AM, Kaplan LM, Davies MJ et al. (2026). Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. PMID: 42814954. doi: 10.1056/NEJMoa2604169.
- Bellido V, le Roux CW, Ekinci EI et al. (2026). Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet. PMID: 42810372. doi: 10.1016/S0140-6736(26)01861-1.
- Zhang X, Belousoff MJ, Liang YL et al. (2021). Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes. Cell Rep. PMID: 34260945. doi: 10.1016/j.celrep.2021.109374.
- Sun B, Willard FS, Feng D et al. (2022). Structural determinants of dual incretin receptor agonism by tirzepatide. Proc Natl Acad Sci U S A. PMID: 35333651. doi: 10.1073/pnas.2116506119.
- Samms RJ, Christe ME, Collins KA et al. (2021). GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice. J Clin Invest. PMID: 34003802. doi: 10.1172/JCI146353.
- Ikushima I, Jensen L, Flint A et al. (2018). A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects. Adv Ther. PMID: 29536338. doi: 10.1007/s12325-018-0677-1.
- Schneck K, Urva S (2024). Population pharmacokinetics of the GIP/GLP receptor agonist tirzepatide. CPT Pharmacometrics Syst Pharmacol. PMID: 38356317. doi: 10.1002/psp4.13099.
- Urva S, Coskun T, Loh MT et al. (2022). LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet. PMID: 36354040. doi: 10.1016/S0140-6736(22)02033-5.
- Dhillon S (2018). Semaglutide: First Global Approval. Drugs. PMID: 29363040. doi: 10.1007/s40265-018-0871-0.
- France NL, Syed YY (2024). Tirzepatide: A Review in Type 2 Diabetes. Drugs. PMID: 38388874. doi: 10.1007/s40265-023-01992-4.
- Bajaj HS, Welch M, Shah P et al. (2026). Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Lancet. PMID: 42250575. doi: 10.1016/S0140-6736(26)00967-0.
- Jastreboff AM, Kaplan LM, FrÃas JP et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity – A Phase 2 Trial. N Engl J Med. PMID: 37366315. doi: 10.1056/NEJMoa2301972.
- Rosenstock J, Frias J, Jastreboff AM et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet. PMID: 37385280. doi: 10.1016/S0140-6736(23)01053-X.
- FrÃas JP, Davies MJ, Rosenstock J et al. (2021). Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. PMID: 34170647. doi: 10.1056/NEJMoa2107519.
- Jastreboff AM, Aronne LJ, Ahmad NN et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. PMID: 35658024. doi: 10.1056/NEJMoa2206038.
- Wilding JPH, Batterham RL, Calanna S et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. PMID: 33567185. doi: 10.1056/NEJMoa2032183.
- Marso SP, Bain SC, Consoli A et al. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. PMID: 27633186. doi: 10.1056/NEJMoa1607141.
- Cummings JL, Atri A, Sano M et al. (2026). Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer’s disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials. Lancet. PMID: 41865758. doi: 10.1016/S0140-6736(26)00459-9.
- Ding M, Li X, Wei Y et al. (2026). Comparative effects of semaglutide tirzepatide and retatrutide on renal fibrosis in UUO and aged mice. iScience. PMID: 42630988. doi: 10.1016/j.isci.2026.117174.
