LIRAGLUTIDE

Summary

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used as a prescription therapeutic for type 2 diabetes and weight management. Mechanistically, it crosses into circumventricular regions and binds neurons in the hypothalamic arcuate nucleus, internalizing in POMC/CART neurons and indirectly inhibiting NPY/AgRP neurotransmission, which mediates its GLP-1 receptor-dependent weight loss ^[2]. In a Phase III randomized controlled trial (SUSTAIN 10), once-weekly semaglutide was superior to once-daily liraglutide 1.2 mg in reducing HbA1c and body weight, with both treatments showing similar safety profiles aside from more frequent gastrointestinal adverse events on semaglutide ^[4]. Preclinical work also suggests liraglutide may attenuate diabetes-associated non-alcoholic fatty liver disease via AMPK/ACC signaling and reduced ferroptosis ^[1] and improve heart-failure-with-preserved-ejection-fraction phenotypes via the Erbb4 pathway in mice ^[3]. Supported by hundreds of RCTs and meta-analyses plus approved prescription status, the human evidence is strong; the liver, HFpEF, and mechanistic findings cited here are from animal/in-vitro models and should not be read as proven human indications.

Sources

1. 1. Liraglutide attenuates type 2 diabetes mellitus-associated non-alcoholic fatty liver disease by activating AMPK/ACC signaling and inhibiting ferroptosis Molecular medicine (Cambridge, Mass.), 2023.
2. 2. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss The Journal of clinical investigation, 2014.
3. 3. Empagliflozin and liraglutide ameliorate HFpEF in mice via augmenting the Erbb4 signaling pathway Acta pharmacologica Sinica, 2024.
4. 4. Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10) Diabetes & metabolism, 2020.

For educational purposes only.