Liraglutide (Saxenda/Victoza) GLP-1 Agonist — Weight & Metabolism
First FDA-approved GLP-1 receptor agonist for chronic weight management, with extensive cardiovascular outcomes data.
Overview
Liraglutide is a GLP-1 receptor agonist with 97% amino acid homology to native GLP-1, modified with a fatty acid side chain (palmitoyl) that enables albumin binding and extends its half-life to approximately 13 hours. FDA-approved as Victoza (1.8 mg daily) for type 2 diabetes and as Saxenda (3.0 mg daily) for chronic weight management, liraglutide was the first GLP-1 agonist approved specifically for obesity (2014). The SCALE clinical trial program demonstrated that liraglutide 3.0 mg daily produces mean weight loss of 8% from baseline at 56 weeks, with approximately one-third of patients achieving >10% weight loss. The LEADER cardiovascular outcomes trial (n=9,340) demonstrated a 13% reduction in major adverse cardiovascular events (MACE) in patients with type 2 diabetes, establishing cardiovascular benefit for the GLP-1 class. While semaglutide has largely supplanted liraglutide in the obesity market due to superior efficacy and weekly dosing, liraglutide remains an important therapeutic option — particularly for patients who do not tolerate semaglutide, prefer daily dosing for more granular dose control, or have insurance coverage for liraglutide specifically. Liraglutide is also approved for pediatric obesity (ages 12+).
Indications
- FDA-approved: Chronic weight management in adults with BMI ≥30 or ≥27 with comorbidity (Saxenda 3.0 mg)
- FDA-approved: Type 2 diabetes mellitus (Victoza 1.2-1.8 mg)
- FDA-approved: Pediatric obesity ages 12+ (Saxenda)
- FDA-approved: Cardiovascular risk reduction in T2DM (LEADER trial)
Mechanism of Action
Binds to and activates GLP-1 receptors in hypothalamus, brainstem, pancreas, and gastrointestinal tract
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Liraglutide (Saxenda) | 0.6 mg | Once daily x 1 week | Starting dose for weight management; dose escalation required |
| Liraglutide (Saxenda) | 1.2 mg | Once daily x 1 week | Week 2 titration dose |
| Liraglutide (Saxenda) | 1.8 mg | Once daily x 1 week | Week 3 titration (also max Victoza diabetes dose) |
| Liraglutide (Saxenda) | 3.0 mg | Once daily | Target maintenance dose for weight management |
Evidence Grade
GRADE A
Safety & Contraindications
- GI side effects: nausea (39%), diarrhea (21%), constipation (19%), vomiting (16%)
- Nausea is dose-dependent and typically improves after 4-8 weeks
- Black box warning: Thyroid C-cell tumors in rodents (MTC risk — do not use in MEN2 or family history of MTC)
- Acute pancreatitis risk (rare, <0.3%)
- Cholelithiasis with rapid weight loss (gallstone risk)
- Tachycardia: mean heart rate increase 2-3 bpm
- Hypoglycemia when combined with insulin or sulfonylureas
- Injection site reactions (erythema, pruritus)