The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.

Orally bioavailable, synthetic nonpeptide agonists (NPAs) of the glucagon-like peptide-1 receptor (GLP-1R) may offer an effective, scalable pharmacotherapy to address the metabolic disease epidemic. One of the first molecules in the emerging class of GLP-1R NPAs is orforglipron, which is in clinical development for treating type 2 diabetes and obesity. Here, we characterized the pharmacological properties of orforglipron in comparison with peptide-based GLP-1R agonists and other NPAs.

An effective approach to tackling complex health policy challenges. Using a clinical microsystems approach and rethinking codesign.

That people with serious mental illness have poor physical health and face a significant life expectancy gap compared with the general population is well known. Despite considerable policy focus in some countries, the gap in life expectancy remains. Tackling complex and persistent health problems such as this requires a systems-based approach, recognising the complexity of interacting components and their effects on the problem and on each other and applying collaborative analysis, design and implementation by those with knowledge of and expertise in the problem and the context.