Obesity, Diabetes and Metabolic Disease Reagents

Obesity and metabolic disorders: from socio-economic impact to next-generation therapeutics

Among metabolic disorders, obesity has become a new pandemic affecting 890 million people according to WHO reports¹ and is on the rise in developed countries where it brings massive socio-economic challenges. Obesity is strongly associated with cardiovascular disorders, cancers, respiratory troubles, etc; and typically, occurs concurrently to other metabolic disorders like Type 2 Diabetes, MASH (Metabolic dysfunction-associated steatohepatitis), and MALFD (Metabolic dysfunction–associated steatotic liver disease) also known as human fatty liver disease. As such, there are important public-health and economic interests in addressing it with therapeutics.

In recent years, Novo Nordisk® and Eli Lilly have disrupted this environment with their successful FDA-approved weight loss medications Semaglutide (GLP-1R agonist) and Tirzepatide (GLP-1R and GIPR dual agonist), which were initially approved for Type 2 Diabetes only.

In the wake of these successes, it is estimated over 60 organizations initiated investigations into 100+ molecules, which set the perspective for the next generation of weight-loss drugs on the 2027 horizon. The next generation of drug candidates are building upon Semaglutide and Tirzepatide by either moving away from injectable peptides in favor of oral small molecules and nanobodies, or by designing peptides exhibiting triple agonism for GLP-1R, GIPR, and GCCR (such as Eli Lilly’s Retatrutide/LY3437943, already undergoing clinical trials).

While Semaglutide, Tirzepatide, and Retatrutide are a benchmark for ongoing and future drug candidates and investigations, the GPCRs they target are far from being the only set of receptors of interest in the race to weight-loss medications. Molecules such as Dapiglutide (GLP-1R and GLP-2R dual agonist), Setmelanotide (MC4R agonist), Cagrilintide (AMYRs agonist), and Monlunabant (CB1R inverse agonist) already demonstrate the potential other receptors hold for weight loss drug treatment.

Revvity has accompanied these developments from the start with a 360° portfolio of assays and reagents dedicated to GPCR and cell signaling pathways related to metabolism, including Gi, Gs, Gq second messengers to Beta-Arrestin recruitment, downstream signaling protein detection, and time-resolved binding assays for pharmacodynamic studies of ligand/receptor interactions. Our assays and reagents fit at multiple stages of the drug discovery process, including screening and are largely referenced in the dedicated literature.^2-8 On top of our GPCR reagents, we also carry an extensive portfolio of diabetes research reagents and MASH & MAFLD research reagents, to investigate the mechanism at play in these critical metabolic disorders that often accompany obesity.