Large-scale human genetic studies have revealed that loss-of-function INHBE variants are associated with a lower abdominal to gluteofemoral fat ratio, improved metabolic profile, and reduced fasting glucose levels.
After finding a mutation in METTL2A in a family with diabetes exhibiting a special phenotype, investigators at Zhejiang University School of Medicine studied its role in glucose and lipid metabolism in METTL2 (murine orthologue) knockout mice and wild-type mice fed a normal chow or a high-fat diet (HFD) for 20 weeks.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has a prevalence of about 25% in the adult population, with steatosis present in >5% of hepatocytes, hepatocyte ballooning and fibrosis as the main hallmarks. Scientists have tested effects of the galectin-3 inhibitor modified citrus pectin (MCP) in ApoE knockout mice fed a western diet.
Targeting monoacylglycerol O-acyltransferase 2 (MGAT2), an enzyme highly expressed in the small intestine, has been validated as an antiobesity strategy in the preclinical setting.
Biolexis Therapeutics Inc. is working on developing orally available, small-molecule AMPK activators that have been found to stimulate AMPK activity as well as dose-dependently enhance glucose uptake in human tissue.
MTX-101 (Mozart Therapeutics Inc.) is a bispecific CD8 Treg modulator that targets CD8 and the KIR2DL family, including KIR2DL1, KIR2DL2 and KIR2DL3, and is being developed for the treatment of CD4-driven autoimmunity and restoring immune balance.
Biomed Industries Inc. has presented data on its IGF-1/GLP-1/GIP/GCGR quadruple agonist NA-931 for the treatment of obesity and metabolic disorders. The company has discovered a family of IGF-1 metabolites, known as NA-931, and its analogues NA-932 and NA-933, which are referred to as NA-931 compounds.
Injectable glucagon-like peptide 1 receptor (GLP-1R) agonists have shown efficacy in weight management and glycemic control. Semaglutide is available as an oral formulation, but it requires specific timing and conditions. Carmot Therapeutics Inc. has presented data for its oral GLP-1R agonist CT-996 from preclinical studies in obesity; the drug is currently in early clinical development.
The obesity market is hot with Novo Nordisk A/S generating $6.3 billion in sales from its semaglutide-containing drugs, Ozempic, Saxenda, Rybelsus and Wegovy, in the first quarter of 2024 and Eli Lilly and Co. bringing in $2.3 billion for its tirzepatide-containing drugs, Zepbound and Mounjaro, in the same quarter. It appears unlikely the market will be a two-horse race for much longer though.
Continuous glucose monitors continue to post positive results for managing diabetes in an ever-expanding population. Long a mainstay of disease management for those with type 1 diabetes, the devices have also proved themselves in treating type 2 diabetes that requires multiple daily injections of insulin.
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