What are the indications for Liraglutide (Glucagon-like peptide-1 (GLP-1) receptor agonist)?

Liraglutide Indications

Liraglutide is FDA-approved for two primary indications: (1) as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus, and (2) to reduce the risk of major adverse cardiovascular events (including heart attack, stroke, and cardiovascular death) in adults with type 2 diabetes mellitus and established cardiovascular disease. 1

Primary FDA-Approved Indications

Glycemic Control in Type 2 Diabetes

• Liraglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus 1
• It can be used as monotherapy or in combination with other antidiabetic medications 2
• Demonstrated A1C reductions up to 1.6% in clinical trials 2

Cardiovascular Risk Reduction

• The FDA specifically approved liraglutide to reduce the risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular death, in adults with type 2 diabetes and established cardiovascular disease 3
• This cardiovascular indication is based on the LEADER trial, which demonstrated a 13% reduction in the primary composite outcome (HR 0.87; 95% CI 0.78–0.97; P = 0.01 for superiority) 3
• Cardiovascular deaths were significantly reduced by 22% (HR 0.78; 95% CI 0.66–0.93; P = 0.007) 3

Dosing Specifications

Adult Patients

• Initiate at 0.6 mg subcutaneously once daily for one week 1
• Increase to 1.2 mg daily after the first week 1
• If additional glycemic control is required, increase to 1.8 mg daily after one week of treatment with the 1.2 mg dose 1

Pediatric Patients (≥10 years)

• Initiate at 0.6 mg subcutaneously once daily for at least one week 1
• Titrate to 1.2 mg daily if additional glycemic control is needed 1
• May increase to 1.8 mg daily after at least one week at the 1.2 mg dose if further control is required 1

Important Limitations of Use

Contraindications

• Patients with a personal or family history of medullary thyroid carcinoma (MTC) 1, 3
• Patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1, 3
• Patients with serious hypersensitivity reactions to liraglutide or any excipients 1
• Not indicated for treatment of type 1 diabetes mellitus 1

Specific Cautions

• Use with caution in patients with history of pancreatitis 3
• Use with caution in patients with severe renal impairment or end-stage renal disease (though no dose adjustment is required; data are limited) 3
• Hypoglycemia risk increases when combined with insulin or insulin secretagogues; dose reduction of these agents may be necessary 1
• In pediatric patients aged 10 years and older, the risk of hypoglycemia was higher with liraglutide regardless of insulin and/or metformin use 1

Clinical Context for Cardiovascular Indication

Patient Selection Criteria

• The cardiovascular benefit was demonstrated in patients with type 2 diabetes at high cardiovascular risk 3
• Over 80% of LEADER trial participants had established cardiovascular disease 3
• Mean age was 64 years with mean diabetes duration of nearly 13 years 3

Cardiovascular Outcomes Evidence

• Reduced all-cause mortality by 15% (HR 0.85; 95% CI 0.74–0.97) 3, 4
• Reduced acute myocardial infarction by 15% (RR 0.85; 95% CI 0.74–0.99) 4
• No significant reduction in stroke was observed (RR 0.86; 95% CI 0.70–1.04) 4
• Reduced worsening nephropathy (HR 0.78; 95% CI 0.67–0.92) 5

Administration Details

• Inject subcutaneously once daily at any time of day, independently of meals 1
• Can be administered in the abdomen, thigh, or upper arm 1
• When using with insulin, administer as separate injections; never mix 1
• Inspect visually prior to each injection; only use if solution is clear, colorless, and contains no particles 1