RT-GLP-3

Perez-Tilve D, Zhang F, Zhang Y, Lohman K, Sorrell J, Vick A, et al.

Molecular metabolism

Using cAMP-signaling assays and diet-induced and GLP-1-receptor-knockout rodent models, this study compared selective GIPR, GCGR, and GLP-1R agonists against retatrutide's balanced triple-receptor activity, applying indirect calorimetry and pair-feeding to separate food-intake suppression from energy-expenditure contributions to body-weight regulation. Retatrutide, used as a triagonist reference compound, normalized body weight in GLP-1-receptor-knockout rodents, supporting a receptor-pharmacology model in which GIPR and GCGR co-agonism can act independently of GLP-1R signaling.

Briand F, Le Cudennec C, Grasset E, Breyner N, Bigot C, Dillard P, et al.

Obesity (Silver Spring, Md.)

In diet-induced mouse and hamster models used to profile the triple GIP/GLP-1/glucagon receptor agonist, administration reduced body weight along with fat and lean mass and reduced short-term food and water intake in mice, while lowering the HOMA-IR insulin-resistance index, hepatic triglyceride content, and cholesterol in both species; in hamsters, receptor engagement also shifted dietary preference toward standard chow over a high-fat/high-cholesterol diet.

Wang S, Liu Y, Yan Z, Huang X, Liao Y, Tang C, et al.

Journal of medicinal chemistry

Using sequence analysis, molecular dynamics simulation, and receptor-binding assays, this study designed and characterized triple GLP-1R/GCGR/GIPR agonist peptides and benchmarked their receptor-activation profiles against retatrutide in diet-induced rodent models, finding that a receptor-biased variant with weaker GIPR engagement produced comparable glycemic and body-composition outcomes to the balanced triagonist — suggesting the ratio of receptor activation, not just absolute potency at each receptor, governs the compound class's pharmacological profile.

Windram M, Lovelock DF, Carew JM, Krieman CG, Hendershot CS, Besheer J

Psychopharmacology (Berl)

In a male and female rat operant drug-discrimination model, acute administration of the triple GIP/GLP-1/glucagon receptor agonist (alongside semaglutide and tirzepatide) attenuated the interoceptive (discriminative-stimulus) effects of alcohol, extending incretin-receptor pharmacology to central interoceptive signaling in a rodent behavioral model.