Liraglutide

A 31-amino-acid GLP-1 receptor agonist with 97% homology to native human GLP-1. Liraglutide is the structural predecessor to semaglutide, engineered with a C-16 palmitic acid at Lys26 via a γ-Glu spacer enabling reversible albumin binding and self-association into heptameric structures at the injection site, producing a ~13-hour half-life suitable for once-daily dosing.

FDA-approved for the treatment of type 2 diabetes (Victoza, Jan 2010), chronic weight management (Saxenda, Dec 2014), and to reduce MACE risk in adults with T2DM and established CVD. The LEADER trial demonstrated a 13% reduction in major adverse cardiovascular events (HR 0.87, P=0.01) and a 22% reduction in cardiovascular death.

The SCALE Obesity and Prediabetes trial showed −8.0% mean weight loss vs −2.6% placebo. Generic versions became available in 2024–2025.

Liraglutide has been evaluated in extensive phase 3 programs. The LEAD trials (1–6) established efficacy for glycemic control in T2DM. The LEADER trial (9,340 patients, median 3.8-year follow-up) demonstrated a 13% reduction in MACE and 22% reduction in cardiovascular death. The SCALE trials established efficacy for chronic weight management: SCALE Obesity and Prediabetes showed −8.0% weight loss; SCALE Diabetes showed 6.0% loss; SCALE Maintenance showed additional 6.2% loss after initial diet-induced loss; SCALE Teens showed 43.3% of adolescents achieved ≥5% BMI reduction.

Secondary LEADER analysis showed reduced macroalbuminuria. Active investigation continues in NAFLD/NASH, PCOS, and neurodegenerative diseases. Off-label uses are not FDA-approved and are under clinical investigation.