Retatrutide vs Tirzepatide: Research Comparison
Retatrutide and tirzepatide are two closely related synthetic peptides developed by Eli Lilly. Both are long-acting incretin-receptor agonists, but they differ in one key respect: tirzepatide activates two receptors (GIP and GLP-1), while retatrutide activates three (GIP, GLP-1 and glucagon). This page compares their structure, mechanism, published research and regulatory status.
Retatrutide
GIP + GLP-1 + glucagon receptors. Investigational compound (LY3437943).
For in vitro research use only. Neither compound supplied by Sterling is for human or animal use. Nothing on this page is medical advice.
At a glance
| Retatrutide | Tirzepatide | |
|---|---|---|
| Receptor targets | GIP, GLP-1 and glucagon (triple agonist) | GIP and GLP-1 (dual agonist) |
| Developer / code | Eli Lilly · LY3437943 | Eli Lilly · LY3298176 |
| Length | 39 amino acids | 39 amino acids |
| Half-life extension | C20 fatty diacid (albumin binding) | C20 fatty diacid (albumin binding) |
| Molecular formula | C221H342N46O68 | C225H348N48O68 |
| Molecular weight | ≈ 4731 g/mol | ≈ 4813.5 g/mol |
| CAS number | 2381089-83-2 | 2023788-19-2 |
| Development stage | Investigational (phase 3 TRIUMPH programme) | Approved prescription medicine (Mounjaro, Zepbound) |
| Quality (Sterling) | Every batch independently tested by Janoshik | Every batch independently tested by Janoshik |
| Research vials | 10mg · 20mg · 40mg | 10mg · 15mg |
Structure
Both peptides are 39 amino acids long and share a similar design strategy. Each is built on an incretin-like backbone, includes non-standard amino acids such as Aib (2-aminoisobutyric acid) to resist enzymatic breakdown, and carries a C20 fatty diacid attached to a lysine side chain through a linker. The fatty acid binds reversibly to albumin, which extends circulation time from minutes to days.
The differences lie in the amino-acid sequence. Tirzepatide’s sequence is based mainly on GIP, tuned to also activate the GLP-1 receptor. Retatrutide’s sequence has further changes, including α-methyl amino acids, that add meaningful activity at the glucagon receptor.
Mechanism: dual vs triple agonism
Tirzepatide (dual)
- GIP receptor: high affinity, comparable to native GIP. The profile is described as “imbalanced” in favour of GIP.
- GLP-1 receptor: biased signalling favouring cAMP over β-arrestin recruitment.
- Studied for glucose-dependent insulin secretion, appetite-related pathways and body weight.
Retatrutide (triple)
- GIP receptor: agonist activity.
- GLP-1 receptor: agonist activity.
- Glucagon receptor: the added component, investigated for effects on energy expenditure, hepatic lipid metabolism and liver fat.
The glucagon component is the main scientific question that separates the two compounds. Researchers are interested in whether adding glucagon-receptor activity changes energy balance and liver fat beyond what dual incretin agonism achieves.
Published research
Tirzepatide
SURPASS programme (phase 3, type 2 diabetes): improvements in glycaemic control versus placebo and active comparators, including semaglutide.
SURMOUNT-1 (NEJM, 2022): 72-week trial in adults with obesity or overweight. Mean weight reductions of 15.0%, 19.5% and 20.9% across three dose groups, versus 3.1% with placebo.
Read more in our tirzepatide research overview.
Retatrutide
Phase 2 obesity trial (NEJM, 2023): 48-week trial in adults with obesity or overweight. Dose-dependent reductions, with mean weight reduction of more than 24% in the highest-dose group, versus around 2% with placebo.
Phase 2a liver-fat study (Nature Medicine, 2024): substantial reductions in liver fat in MASLD.
TRIUMPH programme: phase 3 trials ongoing.
Read more in our retatrutide research overview.
Interpreting the data
- No head-to-head trial. The figures above come from separate trials with different durations (48 vs 72 weeks), populations, designs and phases. They cannot be compared directly.
- Different stages of evidence. Tirzepatide has large phase 3 programmes and regulatory approval. Retatrutide’s published data are mainly from phase 2, with phase 3 results still emerging.
- Similar tolerability themes. Gastrointestinal adverse events were the most commonly reported for both in clinical trials. Increases in heart rate have also been reported with retatrutide.
- Clinical ≠ research-grade. Clinical findings were obtained with pharmaceutical-grade material under medical supervision and do not apply to research reagents.
Regulatory status
Tirzepatide is an approved prescription-only medicine (Mounjaro, Zepbound), authorised by the FDA, EMA and MHRA for specific indications under medical supervision. Retatrutide is investigational and not approved by any regulator.
The research-grade material supplied by Sterling Research is not a licensed medicinal product, is not equivalent to Mounjaro or Zepbound, and is supplied strictly for in vitro laboratory research. It must not be used in humans or animals.
Choosing a compound for research
The choice depends on the research question:
- Tirzepatide is the established reference compound for dual GIP/GLP-1 agonism, with the largest body of published data.
- Retatrutide is suited to studies of triple agonism, and in particular to the additional contribution of glucagon-receptor activity.
- Using both side by side lets researchers isolate the effect of adding the glucagon component.
Related research guides
Frequently asked questions
What is the main difference between retatrutide and tirzepatide?
Tirzepatide is a dual agonist of the GIP and GLP-1 receptors. Retatrutide is a triple agonist that also activates the glucagon receptor.
Are retatrutide and tirzepatide made by the same company?
Yes. Both were developed by Eli Lilly and Company. Tirzepatide is coded LY3298176 and retatrutide is coded LY3437943.
Is retatrutide stronger than tirzepatide?
There is no published head-to-head trial. Reported results come from separate studies with different designs, durations and populations, so they cannot be compared directly.
Which one is approved?
Tirzepatide is an approved prescription medicine (Mounjaro, Zepbound). Retatrutide is investigational and has not been approved by any regulator.
Which sizes does Sterling supply?
Retatrutide is available in 10mg, 20mg and 40mg research vials, and tirzepatide in 10mg and 15mg research vials, for in vitro laboratory use only.
References
- Jastreboff AM, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389:514–526. doi:10.1056/NEJMoa2301972
- Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387:205–216. PubMed 35658024
- Retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024. PubMed 38858523
- Triple G Agonists — A Home Run for Obesity? N Engl J Med. 2023 (editorial). nejm.org
This page is for scientific information only. Sterling Research Group Ltd supplies retatrutide and tirzepatide strictly as research reagents for in vitro laboratory use. They are not licensed medicines, not for human or animal use, and not for diagnostic or therapeutic purposes.