Liraglutide

Liraglutide is a GLP-1 receptor agonist developed by Novo Nordisk, FDA-approved as Victoza for type 2 diabetes (2010) and Saxenda for weight management (2014). It was the first GLP-1 agonist approved specifically for obesity. While it has been largely superseded by semaglutide for weight loss, it remains widely prescribed and has the longest safety track record among GLP-1 agonists, with cardiovascular outcome trial data (LEADER).

Liraglutide shares 97% homology with native GLP-1 but has a fatty acid (C-16 palmitoyl) attached via a glutamic acid spacer, enabling albumin binding and extending its half-life from 2 minutes (native GLP-1) to ~13 hours. It activates GLP-1 receptors in the pancreas (increasing insulin secretion), brain (reducing appetite via hypothalamic action), and gut (slowing gastric emptying). The daily dosing is required due to its shorter half-life compared to weekly semaglutide.

SCALE trials demonstrated ~8% body weight loss over 56 weeks with liraglutide 3.0mg daily. The LEADER cardiovascular outcomes trial (9,340 patients, 3.8 years) showed 13% reduction in major adverse cardiovascular events. Additional studies show benefits for NASH/NAFLD, and potential neuroprotective effects. Common side effects: nausea (39%), diarrhea, constipation. GI side effects typically diminish over 4-8 weeks. Long-term safety data extends over 10+ years of clinical use.