#Small-Molecule-Glp-1

2 stories

Clinical Trials May 10, 2026 · View digest

Ascletis ASC30 Posters at ECO 2026: Once-Monthly Subcutaneous Depot Shows 7.5% Placebo-Adjusted Weight Loss at 16 Weeks

Ascletis announced multiple poster presentations at the 33rd European Congress on Obesity (ECO 2026) opening May 12 in Istanbul. ASC30, a first-in-class small-molecule GLP-1R fully biased agonist developed for once-daily oral and once-monthly to once-quarterly subcutaneous dosing, will be featured across formulation, PK, and clinical-data posters. The Phase 2 13-week study previously reported 7.7% placebo-adjusted weight loss at 60 mg oral dosing; the once-monthly subQ depot formulation achieved 7.5% placebo-adjusted weight loss at 16 weeks after three monthly doses, with topline T2D Phase 2 data expected Q3 2026. The subQ depot angle directly challenges Pfizer's MET-097i monthly thesis with a different mechanism (small-molecule GLP-1R biased agonist vs ultra-long-acting peptide).

Research May 10, 2026 · View digest

Nature (May 6): Brain Reward Circuit Inhibited by Next-Generation Weight-Loss Drugs — UVA Team Shows Small-Molecule GLP-1s Engage Central Amygdala Glp1r+ Neurons

A Nature paper published May 6 from a University of Virginia team developed humanized GLP1R mouse models to investigate how small-molecule GLP1R agonists — including orforglipron (Foundayo) — regulate feeding behavior. Beyond canonical hypothalamic and hindbrain networks that control metabolic homeostasis, the team showed these oral compounds recruit a discrete population of Glp1r-expressing neurons in the central amygdala and selectively suppress consumption of palatable foods by reducing dopamine release in the nucleus accumbens — a parallel hedonic-feeding circuit distinct from the homeostatic mechanism that drives most GLP-1 weight loss. The work explains why patients on small-molecule oral GLP-1s often report reduced food cravings and pleasure-driven eating, and identifies a neural circuit with implications for substance-use disorder and binge eating beyond obesity.