GLP-1, GIP, and glucagon name different receptor axes, not one weight-loss drug class. In the Longeva/Incretin/Tripept catalog each axis maps to a distinct research-use-only (RUO) molecule. This primer is educational, not a human dosing protocol.

Three axes, three molecules

Incretin does not run a retatrutide landing: the commercial triple-agonist cluster sits on Tripept, not on Incretin [1][2].

GLP-1 mono

The GLP-1 receptor is a class B GPCR expressed on pancreatic beta cells, on vagal afferents in the gut, and in select CNS regions (hypothalamus, area postrema). The classic "incretin effect" describes why oral glucose triggers a larger insulin response than an intravenous glucose load of the same size, and GLP-1 together with GIP accounts for that difference.

A GLP-1 agonist's action at this receptor is glucose-dependent: insulin secretion is amplified only when glucose is elevated, glucagon secretion is suppressed in parallel, gastric emptying slows, and a satiety signal reaches the CNS [5]. That glucose dependence is a property of the receptor itself, not of any single drug.

Semaglutide and liraglutide both describe the mono axis in the research catalog but differ in pharmacokinetics because of how the peptide backbone is modified. Fatty-acid acylation and albumin binding extend semaglutide's half-life to roughly 7 days, while the less modified liraglutide has a half-life of about 13 hours. A randomized, placebo-controlled trial of once-weekly semaglutide in the approved clinical population showed a statistically significant reduction in body weight versus placebo [5]; the specific dosing in that trial applied to patients in a clinical program, not to a research-use sample.

Hub editorial: Ozempic ↔ semaglutide. Incretin guide: GLP-1 guide.

GLP-1 + GIP (dual)

The GIP receptor was a contested target for years: some preclinical data pointed toward GIP antagonism as the more promising route in obesity, while tirzepatide was designed as a genuine agonist at both receptors in one molecule. A preclinical series on LY3298176 characterized a balanced dual GLP-1/GIP profile [1], and the SURMOUNT (obesity) and SURPASS (type 2 diabetes) clinical programs studied the INN tirzepatide in approved clinical populations [2].

The unimolecular design means one peptide sequence activates both receptors at once, unlike a hypothetical co-administration of two separate agonists. Tirzepatide's half-life of roughly 5 days supported the once-weekly dosing schedule those programs studied [2]. Exactly how much the GIP component contributes to the weight outcomes, separate from the GLP-1-driven effect, remains an active research question. The RUO vial on Incretin carries the tirzepatide molecule, not the Mounjaro/Zepbound trade name.

Triple agonist (+ glucagon)

Retatrutide (LY3437943) adds glucagon receptor activity on top of GLP-1 and GIP [3][4]. The glucagon receptor is physiologically tied mainly to the liver (glycogenolysis, gluconeogenesis) and to increased energy expenditure, a different mechanism from the largely insulinotropic and satiety-driven effects of GLP-1 and GIP. The rationale for a triple unimolecular agonist is to add an energy-expenditure component on top of the existing appetite and insulin-secretion axes in a single peptide.

Retatrutide's molar mass (~4731 Da) and half-life (~6 days) sit between tirzepatide (~4814 Da, ~5 days) and the native GLP-1 backbone, reflecting the larger, chemically modified scaffold needed to engage three distinct GPCRs at once. Preclinical work and early clinical phases characterized tolerability and receptor balance [3], while phase 2 tracked body-weight trajectories in the approved research population [4]. It is the newest of the three classes by clinical development stage relative to semaglutide and tirzepatide. Within the Longeva network the commercial triple-agonist cluster sits on Tripept, not Incretin.

RUO and COA

Every axis in the research catalog ships as an RUO sample: INN on the label, a COA (certificate of analysis) tied to the LOT with purity data. A batch can be checked independently of an order at verify.longeva.bio using the LOT number.

The clinical trial results this primer cites describe approved drugs in specific study populations under a defined protocol, which is not the same thing as an arbitrary research batch that happens to share a molecule name. A research-use sample is not a medical product and carries no human dosing regimen.

Longeva hub wiki, primer only, does not replace the monograph for an individual molecule.