Retatrutide (GLP-3)
Retatrutide (LY3437943) is an advanced 39-amino acid synthetic peptide that simultaneously activates GLP-1, GIP, and glucagon receptors. This triple-agonist action coordinates appetite suppression, enhanced insulin dynamics, and increased hepatic fat oxidation, producing metabolic effects that significantly exceed those of dual-agonist predecessors.
Key Research Highlights
- Triple-Receptor Action: Synergistically targets GLP-1, GIP, and GCGR to drive thermogenesis, energy expenditure, and glucose-dependent insulin secretion.
- Superior Fat Reduction: Demonstrated exceptional fat mass reduction and hepatic steatosis improvement in clinical models.
- Synergistic Stacking: Pairs with MOTS-c, NAD+, BPC-157, and Tesamorelin for multi-pathway metabolic research.
- Verified Quality: 8mg lyophilized powder, ≥99% HPLC purity, ISO 17025 verified.
Retatrutide (LY3437943; CAS 2381247-38-9; MW ~4676 g/mol) is a 39-amino acid synthetic peptide representing the most advanced generation of incretin-based metabolic research compounds currently in active clinical investigation. Unlike its predecessor compounds — semaglutide (GLP-1 agonist) and tirzepatide (dual GLP-1/GIP agonist) — retatrutide simultaneously activates three distinct metabolic hormone receptors, offering researchers an unprecedented multi-pathway metabolic probe in a single molecule.
The compound is derived from a glucose-dependent insulinotropic polypeptide (GIP) backbone and incorporates three non-coded amino acid substitutions (Aib at positions 2 and 20; alpha-methyl-leucine at position 13) that confer metabolic stability and receptor selectivity. A C20 fatty diacid conjugated at lysine position 17 provides strong albumin binding that dramatically extends plasma half-life, enabling once-weekly dosing intervals in clinical protocols.
At the receptor level, retatrutide's three-point engagement produces coordinated metabolic effects greater than the sum of its parts: GLP-1 receptor activation drives glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, and hypothalamic appetite signaling; GIPR activation enhances insulin dynamics and adipocyte lipid metabolism; glucagon receptor (GCGR) activation promotes hepatic fat oxidation, energy expenditure, and thermogenesis — differentiating retatrutide from dual agonists. This GCGR component is a key driver of superior fat mass reduction and hepatic steatosis improvement seen in clinical data.
In Phase II clinical trials (NEJM, Jastreboff et al., 2023), participants receiving 12 mg weekly achieved mean body weight reduction of 24.2% at 48 weeks. Phase III TRIUMPH trials are ongoing, investigating outcomes in obesity, type 2 diabetes, osteoarthritis, and MASLD.
| Compound | MW / Formula | CAS No. | Sequence / Structure | Receptor / Target |
|---|---|---|---|---|
| Retatrutide (LY3437943) | ~4676 g/mol (acylated) | 2381247-38-9 | 39-AA GIP-backbone; Aib2/Aib20/aMeL13; C20 fatty diacid at Lys17 | Triple GLP-1R / GIPR / GCGR agonist; albumin-binding extended half-life |
The following compounds operate through distinct, non-overlapping mechanisms that complement this product's research pathways. Each is independently available from the General Peptide catalog.
MOTS-c is a unique 16-amino acid peptide encoded by the mitochondrial genome rather than nuclear DNA. It functions as a potent metabolic regulator and "exercise mimetic" by translocating to the nucleus to activate AMPK, optimizing cellular ener...
NAD+ is a vital dinucleotide coenzyme present in all living cells, central to cellular energy, DNA repair, and signaling. It fuels ATP production and acts as the rate-limiting substrate for Sirtuins, PARPs, and CD38 enzymes. Because NAD+ levels...
BPC-157 (Body Protection Compound-157) is a 15-amino acid pentadecapeptide that functions as a potent systemic protector. Exceptionally stable, it activates VEGF/VEGFR2-Akt-eNOS angiogenic signaling, modulates the nitric oxide system, and provi...
This triple-blend combines two Growth Hormone Releasing Hormones (Tesamorelin, CJC-1295) with a selective ghrelin mimetic (Ipamorelin) to maximize pulsatile GH secretion. By targeting pituitary somatotrophs through distinct pathways, it synergi...
5-Amino-1MQ is a potent NNMT (Nicotinamide N-methyltransferase) inhibitor (MW 158.2 g/mol; C10H12N2) that enhances NAD+ biosynthesis and activates sirtuin pathways in adipose tissue. By blocking NNMT, it prevents SAM diversion toward nicotinami...