Liraglutide: The First Daily GLP-1 for Obesity (Victoza, Saxenda)
Once-daily GLP-1 agonist. Victoza (T2D, 2010), Saxenda (obesity, 2014). ~5–8% mean weight loss at one year.
✅ Approved
- Full name
- Liraglutide
- Class
- GLP-1 receptor agonist
- Half-life
- ~13 hours
- Route
- Subcutaneous daily
- Brand names
- Victoza, Saxenda (Novo Nordisk)
- Regulatory status
- FDA — Victoza 2010 (T2D), Saxenda 2014 (obesity). Paediatric approval ≥12 yrs.
What it is
Liraglutide was the first GLP-1 agonist with a fatty-acid modification enabling albumin binding and once-daily dosing. 97% homologous to native GLP-1, with a C16 palmitoyl side chain. Largely superseded in efficacy by semaglutide and tirzepatide but retained for daily dosing preferences and paediatric indications.
How it works
Liraglutide binds GLP-1 receptors to potentiate glucose-dependent insulin release, suppress glucagon, slow gastric emptying, and reduce appetite through central hypothalamic and brainstem circuits.
Shorter half-life (13 h vs 7 days for semaglutide) gives more even day-to-day PK but requires daily injection and produces somewhat less sustained appetite suppression.
What the research shows
The SCALE obesity and LEADER cardiovascular programmes are the primary clinical evidence base.
Pi-Sunyer X et al. (2015) — SCALE Obesity and Prediabetes
Pi-Sunyer X. et al., NEJM 2015;373:11–22. 👥 Human studies
3,731 adults with BMI ≥30 randomised to liraglutide 3.0 mg daily or placebo for 56 weeks.
Mean weight loss −8.4 kg vs −2.8 kg placebo. 63% achieved ≥5% loss, 33% ≥10%.
Limitations: Daily injection; efficacy inferior to weekly semaglutide/tirzepatide; 10% GI-related discontinuation.
Marso SP et al. (2016) — LEADER: cardiovascular outcomes
Marso S.P. et al., NEJM 2016;375:311–322. 👥 Human studies
9,340 T2D patients with high CV risk followed median 3.8 years.
Composite MACE reduced by 13% (13.0% vs 14.9%, HR 0.87, p<0.001). First incretin trial to show cardiovascular benefit in T2D.
Limitations: Effect smaller than later GLP-1 trials; CV benefit not driven by weight loss alone.
Safety and limitations
GI effects (nausea 39%, diarrhoea, vomiting) common during titration. Class-level risks: pancreatitis, gallbladder disease, rodent C-cell tumour signal (contraindicated in MTC/MEN2).
Approved in adolescents aged ≥12 with obesity (SCALE Teens). Generally better tolerated than higher-potency newer agents but requires daily injection.