Researchers from Rivus Pharmaceuticals Inc. presented preclinical efficacy data on RV‑202, a novel oral mitochondrial uncoupler with activity attributed to adenine nucleotide translocase (ANT) activation, in models of obesity.

Although GLP-1 receptor agonists (GLP-1RAs) have significantly advanced obesity treatment, their limitations underscore the need for new therapies that promote weight loss while preserving muscle and supporting metabolic health. Researchers from Rivus Pharmaceuticals Inc. discussed the discovery and preclinical profile of RV-8451, a potentially first-in-class, oral, nonpeptide GLP-1RA.

Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist used in diabetes and obesity, could alleviate depression through a pathway that does not depend on the GLP-1 receptor but instead on the gut microbiota, since the treatment increases the presence of the bacterium Lactobacillus delbrueckii.

IBI-3032 is a nonpeptide GLP-1 receptor agonist under development at Innovent Biologics Co. Ltd. for the potential treatment of obesity and other metabolic diseases. The company recently reported results of preclinical studies in which pharmacokinetic profiling was performed in vivo in different species, and the candidate’s in vivo efficacy was tested in a murine model with diet-induced obesity.

Researchers from Innovent Biologics (Suzhou) Co. Ltd. presented preclinical efficacy data on IBI-3040, a dual agonist of amylin and calcitonin receptors (CTR). In vitro studies in UM-UC-3 cells expressing human CTR and amylin receptor subtypes AMY-1 and AMY-3 showed that IBI-3040 elicited robust receptor activation, as evidenced by cAMP accumulation assays.

Clinical evidence supports the integration of dual amylin and calcitonin receptor agonism (DACRA) with GLP-1, GIP and glucagon receptor signaling (triple G) as a synergistic approach for appetite modulation, insulin sensitivity and weight loss. Oban Biopharma Inc. is developing OBT-676, an oral small molecule that delivers full DACRA activity with triple G partial agonism for the treatment of metabolic disorders.