Study summary · research use only
Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study examined the long-acting NPY2R agonist BI 1820237 alone and combined with the GCGR/GLP-1R dual agonist survodutide, in lean mice and diet-induced obese mice. BI 1820237 dose-dependently reduced food intake and gastric emptying in lean mice. Significant bodyweight reductions were not observed with BI 1820237 alone in diet-induced obese mice; however, combination with survodutide was associated with a 22% bodyweight reduction, significantly (p < 0.01) greater than the 17% reduction with survodutide alone. Regression-based interaction analysis found BI 1820237 increased the effect of survodutide by 265% at an ED50 of 11.7 nmol/kg across a range of dose combinations. The authors describe combined NPY2R and GCGR/GLP-1R agonism as a mode of action associated with weight loss in mice with obesity.
Abstract
Nutrient-stimulated gut hormone peptide YY3-36 (PYY3-36) selectively activates the neuropeptide Y2 receptor (NPY2R) and reduces energy intake in humans. We describe the discovery and pharmacology of the long-acting NPY2R agonist BI 1820237 and its potential bodyweight-lowering efficacy alone and in combination with the glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) dual agonist survodutide. BI 1820237 dose-dependently reduced food intake and gastric emptying in lean mice. Significant bodyweight reductions were not observed with BI 1820237 alone in diet-induced obese mice, however combination with survodutide led to bodyweight reduction of 22% which was significantly (p < 0.01) greater than the 17% bodyweight reduction with survodutide alone. Regression-based interaction analysis demonstrated that BI 1820237 increased the efficacy of survodutide by 265% at an ED50 of 11.7 nmol/kg over a range of dose combinations. Synergistic NPY2R and GCGR/GLP-1R agonism provides an attractive mode of action for clinically relevant weight loss in patients with obesity.
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