Liraglutide

Overview

Liraglutide is an FDA-approved GLP-1 receptor agonist marketed as Victoza (type 2 diabetes, approved 2010) and Saxenda (chronic weight management, approved 2014). It was the first GLP-1 analog approved for obesity and carries an FDA boxed warning for the risk of thyroid C-cell tumors. Pediatric indications include type 2 diabetes in patients ≥10 years (Victoza) and obesity in patients ≥12 years with BMI ≥95th percentile (Saxenda).

Mechanism of Action

Liraglutide shares 97% homology with native GLP-1 and binds to the GLP-1 receptor to stimulate glucose-dependent insulin secretion, suppress glucagon release, slow gastric emptying, and reduce appetite via hypothalamic signaling. A C16 palmitic acid modification enables non-covalent albumin binding, extending its half-life to approximately 13 hours and supporting once-daily subcutaneous dosing.

Research Summary

The SCALE Obesity and Prediabetes trial (Pi-Sunyer et al., NEJM 2015; PMID 26132939) demonstrated ~8% body-weight loss with Saxenda 3.0 mg over 56 weeks, and the SCALE Diabetes trial (Davies et al., JAMA 2015; PMID 26284720) showed 6.0% weight loss in adults with type 2 diabetes. The LEADER cardiovascular outcomes trial (Marso et al., NEJM 2016; PMID 27295427) showed a 13% reduction in major adverse cardiovascular events in type 2 diabetes with established CVD or high CV risk. A pediatric Phase 3 trial (Kelly et al., NEJM 2020; PMID 32233338) supported Saxenda's approval for adolescents ≥12 years.

Dosing Information

Reported Side Effects

• Nausea (very common, usually transient during titration)
• Vomiting and diarrhea
• Constipation, dyspepsia, abdominal pain
• Headache, fatigue
• Injection-site reactions
• Hypoglycemia (when combined with insulin or sulfonylureas)
• Increased heart rate (2–3 bpm)
• Gallbladder disease (cholelithiasis/cholecystitis)
• Acute pancreatitis (rare but label warning)
• Acute kidney injury from volume depletion
• Anti-liraglutide antibody formation

Research References

• A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE Obesity and Prediabetes; Pi-Sunyer et al., NEJM 2015) (2015)
• Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial (Davies et al., JAMA 2015) (2015)
• Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER; Marso et al., NEJM 2016) (2016)
• A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity (Kelly et al., NEJM 2020) (2020)