Compounds / GLP-1 agonists

Liraglutide

Liraglutide (Victoza / Saxenda)

First-generation once-daily GLP-1 receptor agonist, structurally close to native GLP-1 (97% homology) with a fatty acid side chain enabling albumin binding. Approved as Victoza for T2D (2010, including pediatrics 10+) and as Saxenda for chronic weight management (2014, including pediatrics 12+). Now largely displaced by once-weekly semaglutide and tirzepatide in adults but retains relevance for pediatric obesity and patients who prefer titration flexibility of daily dosing.

At a glance

Half-life

~13 h ~13h SC. Steady state in 3 days of once-daily dosing. Shorter t½ allows quick discontinuation if AEs. Tmax 8-12h post-SC injection (median ~11h). Bioavailability ~55%.

Tmax

~11 h

Routes

SubQ

Evidence base

3 studies 3 human

Mechanism

GLP-1 analogue (97% sequence homology) acylated with palmitic acid via a glutamic acid spacer, enabling >98% reversible albumin binding. Albumin binding extends t½ from ~2 min (native GLP-1) to ~13 hours, supporting once-daily dosing. Acts through GLP-1 receptor: glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, hypothalamic POMC/CART neuron activation suppressing appetite. Heptamer self-association at injection site provides additional protraction. LEADER trial: 13% relative risk reduction in MACE in T2D with CVD. SCALE obesity trial: -8.4 kg (63% achieved ≥5% loss) vs -2.8 kg placebo. Adolescent obesity label extended.

Dosing

Where a study reports an amount, it appears in that study's entry below, attributed to the source.

Published evidence

1. Human RCT 2020

   A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity

   Kelly AS, Auerbach P, Barrientos-Perez M, et al. NEJM

   n=251 adolescents 12-17, 56 weeks: liraglutide 3.0mg BMI -4.64% vs placebo -1.97%. Basis of Saxenda pediatric label.

   PMID 32320621

2. Human RCT 2016

   Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER)

   Marso SP, Daniels GH, Brown-Frandsen K, et al. NEJM

   LEADER (n=9,340 T2D + high CV risk, median 3.8 yr): liraglutide reduced MACE 13% (HR 0.87) and CV death 22% (HR 0.78). Established cardio-protection of GLP-1 RA class.

   PMID 27295427

3. Human RCT 2015

   A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE Obesity and Prediabetes)

   Pi-Sunyer X, Astrup A, Fujioka K, et al. NEJM

   n=3,731 obesity, 56 weeks: liraglutide 3.0mg -8.4 kg vs placebo -2.8 kg. 63% achieved ≥5% loss vs 27%. Basis of Saxenda approval.

   PMID 26132939

Reported side effects

Nausea

Very common Moderate · 39% in Saxenda SCALE trials; 28% in Victoza T2D. Peaks in titration.

Diarrhea

Common Mild · 20% in SCALE; 17% in Victoza.

Constipation

Common Mild · 19% in SCALE.

Vomiting

Common Moderate · 16% in SCALE.

Hypoglycemia (T2D w/ SU/insulin)

Common Serious · Saxenda + T2D + SU: 43% experienced hypoglycemia. Without DM/secretagogue: rare but reported.

Headache

Common Mild · 14% in SCALE.

Decreased appetite

Common Mild · Wanted effect; 10% reported as AE.

Increased lipase

Common Moderate · Mean 21% increase from baseline; clinical significance debated.

Heart rate increase (2-3 bpm)

Common Mild · Mean +2-3 bpm; 6.4% had HR increase >20 bpm above baseline. Etiology unclear.

Cholelithiasis

Common Moderate · Saxenda 2.2% vs placebo 0.8%; cholecystitis 0.8% vs 0.4%. Risk amplified by rapid weight loss.

Pancreatitis

Rare Serious · Saxenda: 9 cases (0.4 events/1000 pt-yr) vs 2 placebo. The Saxenda label directs discontinuation if pancreatitis is suspected.

Acute kidney injury

Rare Serious · Volume-depletion mediated, esp during titration GI losses.

Suicidal behavior and ideation

Rare Serious · Saxenda label retains monitoring requirement (legacy from anti-obesity drug class warnings). 9 events in Saxenda vs 2 placebo. FDA 2024 review found NO causal link for GLP-1 RA class; FDA has requested removal of the warning.

Thyroid C-cell tumors

Rare Serious · BOXED WARNING. Rodent carcinogenicity; cases of MTC reported postmarket but causality unestablished. Contraindicated with personal/family hx of MTC or MEN-2.

Interactions

• Insulin or sulfonylurea Synergy

  Increased risk of hypoglycemia, especially severe.

• Oral medications (general) Absorption interference

  Liraglutide may modestly affect absorption of co-administered oral drugs (acetaminophen Cmax reduced ~13-23%); much less than tirzepatide.

• Semaglutide (SC) Redundant

  Same drug class: additive AE burden, no efficacy advantage. Concurrent GLP-1 RA use is not recommended.

Reconstitution and storage

Multi-dose pre-filled pen (18 mg / 3 mL = 6 mg/mL). No reconstitution.

Unused pens: refrigerate 36-46°F (2-8°C). In-use pens: room temp ≤86°F (30°C) or refrigerated for up to 30 days. Protect from light and heat. Discard 30 days after first use.

Open the reconstitution calculator for Liraglutide