Liraglutide

Liraglutide (also known as Victoza, Saxenda, NN2211) is a metabolic research peptide. The GLP-1 that proved the class. A C16 palmitoyl chain gave native GLP-1 a 13-hour half-life instead of two minutes — and produced the first cardiovascular outcome data for the family.

Liraglutide is a GLP-1 analogue with 97% sequence homology to human GLP-1, modified by an Arg34Lys substitution and acylation of Lys26 with a C16 palmitic acid via a γ-glutamyl spacer. That acylation drives albumin binding and self-association at the injection site, extending the half-life from roughly 2 minutes (native GLP-1) to approximately 13 hours — enough for once-daily dosing. Approved as Victoza (type 2 diabetes, 2010) and Saxenda (obesity at 3.0 mg, 2014), liraglutide established the clinical template the entire GLP-1 class followed. The SCALE obesity programme reported approximately 8% mean weight reduction at 56 weeks with 3.0 mg daily versus 2.6% on placebo, and the LEADER cardiovascular outcomes trial (N=9,340) demonstrated a 13% reduction in major adverse cardiovascular events in type 2 diabetes — the first such result for a GLP-1 agonist. It has since been superseded in efficacy by weekly agents (semaglutide, tirzepatide), but remains the most extensively characterised GLP-1 in terms of long-term safety data and is available as a generic in several markets.

1 Mechanism of action

Agonises GLP-1 receptors on pancreatic β-cells (glucose-dependent insulin secretion), α-cells (glucagon suppression), the gastric antrum (delayed emptying) and hypothalamic/brainstem appetite centres. Palmitoylation enables albumin binding and heptamer self-association, protecting against DPP-4 degradation and renal clearance.

Primary targets: GLP-1R

2 Reported effects

Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.

2.1 Reported benefits

• ~8% mean weight reduction at 56 weeks (SCALE, 3.0 mg)
• 13% reduction in major adverse cardiovascular events (LEADER)
• Robust HbA1c reduction with low intrinsic hypoglycaemia risk
• Daily dosing allows rapid titration and fast washout
• The longest-running human safety dataset of any GLP-1 agonist
• Available generically in several markets

2.2 Side effects

• Nausea, vomiting, diarrhoea, constipation (most common, escalation-dependent)
• Injection site reactions
• Gallbladder disease including cholelithiasis and cholecystitis
• Pancreatitis (rare)
• Increased heart rate
• Hypoglycaemia when combined with insulin or sulfonylureas

3 Chemical and physical properties

3.1 Amino acid sequence

4 Research dosages

Type 2 diabetes: 0.6 mg daily escalating to 1.2–1.8 mg. Obesity: escalate weekly by 0.6 mg to 3.0 mg SC daily.

5 Research studies (8)

1. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE)
   New England Journal of Medicine (2015) · RCT · N=3,731
   56-week trial of liraglutide 3.0 mg daily in adults with obesity or overweight without diabetes.
   Key finding: 8.0% mean weight loss vs 2.6% placebo; 63.2% achieved ≥5% weight loss vs 27.1% on placebo.
2. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER)
   New England Journal of Medicine (2016) · RCT · N=9,340
   Cardiovascular outcomes trial over a median 3.8 years in high-risk type 2 diabetes.
   Key finding: 13% reduction in major adverse cardiovascular events and 22% reduction in cardiovascular death — first CV benefit demonstrated for a GLP-1 agonist.
3. A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults.
   Nature medicine (2025) · Systematic Review
   This systematic review and network meta-analysis evaluated the efficacy and safety of obesity management medications (OMMs) in terms of reducing body weight and impact on obesity-related complications.
4. Liraglutide for Children 6 to <12 Years of Age with Obesity - A Randomized Trial.
   The New England journal of medicine (2025) · RCT
   Among children (6 to <12 years of age) with obesity, treatment with liraglutide for 56 weeks plus lifestyle interventions resulted in a greater reduction in BMI than placebo plus lifestyle interventions.
5. The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines.
   Expert opinion on investigational drugs (2025) · Review
   GLP-1-based therapies have changed the treatment of overweight/obesity.
6. Effect of the glucagon-like peptide-1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes.
   Diabetes, obesity & metabolism (2023) · RCT
   Although both liraglutide and CR are valuable strategies for cardiometabolic risk reduction, CR was associated with greater weight loss and more favourable improvements in body composition than treatment with...
7. Liraglutide 3 mg on weight, body composition, and hormonal and metabolic parameters in women with obesity and polycystic ovary syndrome: a randomized placebo-controlled-phase 3 study.
   Fertility and sterility (2022) · RCT
   LIRA 3 mg once daily appears superior to PL in reducing BW and androgenicity and improving cardiometabolic parameters in women with PCOS and obesity.
8. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined.
   The New England journal of medicine (2021) · RCT
   A strategy combining exercise and liraglutide therapy improved healthy weight loss maintenance more than either treatment alone.

6 Safety and risk profile

6.1 Regulatory status

Liraglutide is currently classified as FDA approved. Approval applies to specific clinical indications and dosing; research-grade material is not the approved product.

Safety score: 84/100 — low concern. Derived from clinical data volume, known risks and regulatory status.

6.2 Contraindications

Conditions and populations in which use is contraindicated:

• Personal or family history of medullary thyroid carcinoma
• Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
• History of pancreatitis
• Pregnancy or lactation
• Type 1 diabetes mellitus / diabetic ketoacidosis

6.3 Drug interactions

6.4 Long-term risks

• Thyroid C-cell tumours in rodents; human relevance remains unresolved
• Gallbladder disease with sustained rapid weight loss
• Loss of lean mass during weight reduction
• Weight regain on discontinuation

6.5 Research best practices

• Store unopened at 2–8 °C; in-use pens typically stable at room temperature for 30 days
• Escalate at weekly intervals — GI effects are almost entirely escalation-driven
• Rotate injection sites to reduce lipohypertrophy
• Monitor for gallbladder symptoms during rapid weight loss phases

7 Frequently asked questions

Why would anyone use liraglutide over semaglutide?

Daily dosing gives finer control and faster washout if adverse effects appear, and liraglutide has the longest real-world safety record in the class. It is also available generically in some markets, making it substantially cheaper. Efficacy is clearly lower — roughly 8% vs ~15% weight reduction.

What is the difference between Victoza and Saxenda?

Same molecule, different maximum dose and indication: Victoza is dosed up to 1.8 mg daily for type 2 diabetes, Saxenda up to 3.0 mg daily for weight management.

How significant was the LEADER trial?

It was the first demonstration that a GLP-1 receptor agonist reduces cardiovascular events, shifting the class from glucose-lowering agents to cardiometabolic therapies and setting up the later SELECT trial with semaglutide.

8 References

1. A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults. PubMed (2025). McGowan B, et al.. View source
2. Liraglutide for Children 6 to <12 Years of Age with Obesity - A Randomized Trial. PubMed (2025). Fox CK, et al.. View source
3. The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines. PubMed (2025). Madsbad S, et al.. View source
4. Effect of the glucagon-like peptide-1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes. PubMed (2023). Silver HJ, et al.. View source

9 See also

• Peptide encyclopedia index
• Peptide reconstitution calculator
• Glossary of peptide research terms