Liraglutide

Approved Indications:

• Type 2 Diabetes Mellitus (Adults and Adolescents ≥10 years):
  As an adjunct to diet and exercise to improve glycemic control.
• Chronic Weight Management (Adults and Adolescents ≥12 years):
  As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in:
• Adults with a BMI ≥30 kg/m² (obese), or ≥27 kg/m² (overweight) with at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes, dyslipidemia).
• Adolescents ≥12 years with obesity (BMI ≥95th percentile for age and sex).
• Cardiovascular Risk Reduction:
  To reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes and established cardiovascular disease.

Clinically Accepted Off-Label Uses:

• Polycystic Ovary Syndrome (PCOS):
  For metabolic improvement and weight loss in overweight/obese women with PCOS (investigational use).

Type 2 Diabetes (Adults):

• Start with 0.6 mg subcutaneously once daily for 1 week.
• Increase to 1.2 mg once daily.
• If additional glycemic control is needed, increase to 1.8 mg once daily.
• Maximum dose: 1.8 mg/day.

Weight Management (Adults):

• Start at 0.6 mg once daily, increase by 0.6 mg weekly to reach 3 mg once daily by week 5.
• Maintain at 3 mg once daily.

Adolescents (≥12 years, Obesity):

• Dose titrated similarly to adults.
• Maximum dose: 3 mg once daily.

Pediatrics (10–17 years, Type 2 Diabetes):

• Start with 0.6 mg once daily, titrated up to 1.8 mg/day.

Elderly:

• No dosage adjustment required. Monitor renal function and tolerability.

Renal Impairment:

• Mild to moderate: No adjustment needed.
• Severe: Use with caution.

Hepatic Impairment:

• Use with caution; limited data available.

Administration:

• Administer subcutaneously once daily in the abdomen, thigh, or upper arm, with or without food.
• Rotate injection sites to reduce risk of lipodystrophy.

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It mimics endogenous GLP-1 and binds to GLP-1 receptors in the pancreas, stimulating glucose-dependent insulin secretion, suppressing glucagon release, and slowing gastric emptying. These actions improve postprandial and fasting glucose control. Liraglutide also acts on the hypothalamus to reduce appetite and energy intake, contributing to weight loss. Cardiovascular benefits are thought to result from anti-inflammatory, anti-atherogenic, and endothelial-protective effects.

• Absorption: ~55% bioavailability. Peak plasma concentration: 8–12 hours after subcutaneous injection.
• Distribution: Volume of distribution: 11–17 L. Highly protein-bound (>98%).
• Metabolism: Metabolized via general proteolytic pathways; not CYP450-mediated.
• Elimination: Metabolites excreted in urine and feces.
• Half-life: ~13 hours, supporting once-daily dosing.
• Onset: Glycemic control improves within days; weight loss effects develop over weeks.

• Pregnancy:
  Not recommended during pregnancy. Based on animal studies, may cause fetal harm. Discontinue at least 1 month before a planned pregnancy.
• Lactation:
  Unknown if liraglutide is excreted into human milk. Use is not recommended due to potential effects on the nursing infant.
• Caution:
  Use effective contraception during treatment. Avoid use during pregnancy and lactation unless clearly indicated.

• Primary Class: GLP-1 Receptor Agonist
• Subclass: Incretin mimetic for glycemic control and weight management

• Personal or family history of medullary thyroid carcinoma (MTC)
• History of multiple endocrine neoplasia syndrome type 2 (MEN 2)
• Hypersensitivity to liraglutide or formulation components
• Pregnancy (for weight management indication)

• Thyroid C-cell Tumors: Boxed warning. Avoid in patients with MTC or MEN 2.
• Pancreatitis: Cases reported. Discontinue if suspected.
• Cholelithiasis/Cholecystitis: Increased risk; monitor for abdominal symptoms.
• Hypoglycemia: Especially when used with insulin or sulfonylureas.
• Renal Impairment: Monitor for dehydration or acute kidney injury.
• Suicidal Behavior: Monitor for depression or suicidal thoughts (especially in adolescents).
• Gastrointestinal Effects: Common; may reduce with dose titration.

Common:

• Gastrointestinal: Nausea, vomiting, diarrhea, constipation, abdominal pain
• CNS: Headache, dizziness, fatigue
• Metabolic: Decreased appetite, weight loss

Serious:

• Pancreatitis
• Cholelithiasis or cholecystitis
• Hypoglycemia (with insulin/sulfonylureas)
• Acute kidney injury
• Suicidal ideation (in obesity treatment)

Rare:

• Angioedema
• Anaphylaxis
• Possible medullary thyroid carcinoma (animal data)

Onset:
Most GI side effects occur early in treatment and may resolve over time.

• Insulin/Sulfonylureas: Risk of hypoglycemia; dose adjustment may be needed.
• Delayed Gastric Emptying: May affect absorption of oral drugs with narrow therapeutic index (e.g., warfarin, digoxin).
• No significant CYP450 interactions.
• Alcohol: May exacerbate GI effects or worsen glycemic control.

• ADA Standards of Care 2024: Recommends GLP-1 receptor agonists like liraglutide for patients with type 2 diabetes and atherosclerotic cardiovascular disease or obesity.
• NICE Guidelines: Liraglutide is approved for weight management when lifestyle interventions fail.
• FDA Safety Updates: Reinforces boxed warning on thyroid C-cell tumors; monitoring and REMS programs in place.

• Unopened Pens: Store in refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect from light.
• In-use Pens: Store at 15°C to 30°C (59°F to 86°F) for up to 30 days.
• Discard if frozen.
• Always cap the pen to protect from light when not in use.