apelin + GLP-1

The combination of apelin (or an apelin receptor [APJ] agonist) and glucagon-like peptide-1 (GLP-1) receptor agonists is an investigational therapeutic strategy designed to address a major limitation of GLP-1-driven weight loss: the loss of lean body mass and skeletal muscle (sarcopenic obesity). Apelin is an exercise-induced peptide (exerkine) that promotes muscle anabolism, mitochondrial biogenesis, and glucose uptake via the APJ receptor, thereby preserving muscle mass and function. GLP-1 receptor agonists promote weight loss and glycemic control by suppressing appetite and delaying gastric emptying. Combining these two pathways synergistically enhances fat loss and glycemic control while preventing muscle atrophy. Several approaches are in development, including co-administration of the oral APJ agonist azelaprag (developed by BioAge Labs, though its Phase II STRIDES trial with tirzepatide was discontinued in late 2024 due to liver safety concerns), transdermal co-formulations like Anodyne Nanotech's apelin/GLP-1 patch, and unimolecular dual GLP-1/APJ receptor co-agonists such as exendin-linker-apelin (ELA) developed by Ulster University.

Other names

apelin + GLP-1 receptor agonistapelin + glucagon-like peptide-1apelin/GLP-1apelin/GLP-1 combinationAPJ agonist + GLP-1 receptor agonistELAexendin-linker-apelin