Single agonists of the glucagon-like peptide-1 receptor (GLP-1R) have been a success in the treatment of obesity, but monomeric dual or triple agonists have demonstrated improved efficacy on energy intake, appetite or metabolic function.
Oxyntomodulin (OXM) is a peptide hormone released by intestinal L cells after food intake. It acts as a dual agonist of glucagon-like peptide 1 (GLP-1) and glucagon receptors, regulating appetite, energy expenditure and glucose metabolism. However, its short plasma half-life limits its therapeutic potential.
Adipose tissue is essential for energy balance, but its dysfunction due to excessive lipid accumulation contributes to metabolic disorders such as insulin resistance, dyslipidemia and type 2 diabetes. Thus, regulating adipogenesis represents a promising strategy for combating obesity-related complications.
Glucagon-like peptide 1 receptor (GLP-1R) agonism is a validated approach for treating obesity. ECC-4703 is a small molecule and liver-targeting compound developed by Eccogene Co. Ltd. It is an agonist of thyroid hormone receptor β (THR-β) and its metabolic impact on preclinical models of obesity in combination with semaglutide was investigated.
ASC-47 is a thyroid hormone receptor β agonist, muscle-preserving weight loss compound for treating obesity developed by Ascletis Pharma Inc. ASC-47 demonstrated a half-life of 26 and 40 days in healthy subjects and in patients with obesity, respectively.
Therapies based on glucagon-like peptide 1 (GLP-1) are the most effective for treating obesity to date, but their efficacy and tolerability are limited by gastrointestinal side effects and compensatory reduction of energy expenditure.
Synthetic mitochondrial protonophores uncouple ATP production, increasing tricarboxylic acid (TCA) cycle activity and fat oxidation to meet energy demands. This approach promotes weight loss and may also enhance glycemic control and lipid metabolism.
Mira Pharmaceuticals Inc. has announced new animal study results with SKNY-1, highlighting its potential as an oral therapeutic to address both obesity and nicotine addiction. This follows the recent report of in vitro data on SKNY-1.
Innovent Biologics Inc. announced June 27 that it gained National Medical Products Administration’s (NMPA) approval of mazdutide as a new weight loss therapy for obese or overweight patients in China. Mazdutide is a dual glucagon/glucagon-like peptide-1 (GCG/GLP-1) receptor agonist originally discovered by Eli Lilly and Co., of Indianapolis.