GIP — glucose-dependent insulinotropic polypeptide — is the second incretin receptor that, alongside GLP-1, drives the dual-agonist drugs (tirzepatide). It contributes additional insulinotropic activity, gastric-emptying effects, and adipose-tissue signaling that compounds the GLP-1 effect on weight loss.
Beyond tirzepatide, GIP-targeting work covered on this site includes earlier-stage GIP-only and GIP-antagonist programs (Crinetics, Amgen's MariTide GLP-1/GIPR approach, and Novo's earlier GIPR program). The biology has been controversial — GIPR agonism vs antagonism produces different metabolic outcomes depending on context.
Stories here cover the GIP-receptor pipeline, mechanism papers, and the broader incretin biology. See #tirzepatide for the lead clinical asset.
On July 5, Ascletis submitted two INDs to the FDA: ASC36, a peptide amylin receptor agonist dosed once monthly to once quarterly by injection, and ASC36_35, a co-formulation pairing ASC36 with the GLP-1R/GIPR agonist peptide ASC35. In diet-induced obese rat studies, ASC36 monotherapy showed roughly 91% and 32% greater relative body-weight reduction than petrelintide and eloralintide, and the ASC36_35 combination showed about 51% greater reduction than co-administered eloralintide plus tirzepatide. The filings push amylin biology further into the obesity race.
A Nature paper from Liskiewicz, DiMarchi, Tschöp, Müller and colleagues introduces a unimolecular peptide-drug conjugate that combines a GLP-1R/GIPR co-agonist peptide with the pan-PPAR (α/γ/δ) agonist lanifibranor via a pH-sensitive linker. After receptor-mediated internalization, the linker cleaves and lanifibranor escapes to the nucleus to activate PPARs while the peptide moiety drives GLP-1R/GIPR signaling at the membrane. In obese, diabetic mice the conjugate produced greater weight loss and insulin sensitization than equimolar dosing of the unconjugated peptide and lanifibranor, without the typical PPAR-related cardiac and weight-gain safety signals.
Obesity biotech Kailera Therapeutics priced an upsized IPO of 39.06 million shares at $16, raising $625 million — the largest venture-backed biopharmaceutical IPO since Acelyrin in 2023. Lead candidate ribupatide (a GLP-1/GIP peptide dual agonist) drove 18% body weight loss at 48 weeks in a late-stage Chinese study; global Phase 3 readout expected in 2028.
Richard DiMarchi and Matthias Tschöp — whose work enabled Eli Lilly's Zepbound and the modern GLP-1 class — published a peer-reviewed draft paper arguing that targeting GIP and glucagon receptors alone, without GLP-1, may deliver comparable weight loss without the nausea and vomiting that plague current therapies. The experimental molecule, backed by BlueWater Biosciences, challenges the central dogma of obesity drug design. Results are preclinical and must still translate to humans.
Viking enrolled ~1,000 adults in the 78-week trial of VK2735, a GLP-1/GIP dual agonist. Phase 2 showed up to 14.7% body weight reduction in just 13 weeks.