Generic Name

Liraglutide

Mechanism

• Liraglutide is a long‑acting analog of glucagon‑like peptide‑1 (GLP‑1).
• It binds to the GLP‑1 receptor on pancreatic β‑cells, leading to:
• Stimulation of insulin secretion in a *glucose‑dependent* manner.
• Suppression of glucagon release when glucose is elevated.
• Slowing of gastric emptying, which delays nutrient absorption and reduces post‑prandial glucose excursions.
• Central appetite suppression via hypothalamic pathways, promoting satiety and weight loss.
• Its prolonged half‑life (≈13 h) enables once‑daily dosing and maintains receptor occupancy throughout the day.

Pharmacokinetics

Indications

• Type 2 Diabetes Mellitus (T2DM) – adjunct to diet & exercise; indicated in adults with inadequate glycemic control on basal insulin *or* oral agents.
• Chronic Weight Management (Obesity) – indicated for adults with BMI ≥ 30 kg/m² *or* BMI ≥ 27 kg/m² with at least one weight‑related comorbidity.
• Glucagon‑like Peptide‑1 (GLP‑1) Receptor Modulation – marketed as *Victoza* (T2DM) and *Saxenda* (obesity).

Contraindications

• Contraindications
• Personal or family history of *medullary thyroid carcinoma (MTC)* or Multiple Endocrine Neoplasia type 2 (MEN 2).
• Known hypersensitivity to liraglutide or any component of the formulation.
• Warnings
• Suspected Pancreatitis – abdominal pain, nausea, vomiting; obtain serum amylase/lipase before initiation and when symptoms present.
• Gallbladder Disease – cholelithiasis, cholecystitis.
• Hypoglycemia Risk – especially when combined with insulin or sulfonylureas.
• Kidney Function – monitor in severe renal impairment; may require dose adjustment for *Saxenda* in extreme cases (FDA).
• Pregnancy Category B – insufficient data in humans; generally avoid.
• Breastfeeding – limited data; discuss benefits vs. unknown risks.

Dosing

T2DM (Victoza)

1. Initiation: 0.6 mg SC once daily (no loading dose).

2. Titration: Increase to 1.2 mg after ≥4 weeks if HbA1c > 7.0 % (or clinical target).

3. Max dose: 1.8 mg SC daily (cumulative dose 43 mg/month).

Obesity (Saxenda)

1. Initiation: 0.6 mg SC once daily for 4 weeks.

2. Titration: 1.2 mg after 4 weeks, 1.8 mg after 8 weeks, 2.4 mg after 12 weeks, and 3.0 mg after 16 weeks.

3. Maintenance: 3.0 mg SC daily (cumulative dose 108 mg/month).
• Injection Technique
• Rotate sites: abdomen, thigh, upper arm.
• Use 4‑mm or 5‑mm needles; thinner needles reduce discomfort.
• Maintain sterility; store at 2–8 °C (4 °C ± 1 °C) after first use; discard unused vial after 56 days.

Adverse Effects

Common (≥ > 10 %)
• Nausea, vomiting, diarrhea, constipation
• Abdominal pain
• Injection‑site reactions (pain, pruritus, erythema)
• Headache
• Dizziness

Serious (rare)
• Pancreatitis – abdominal pain radiating to back, vomiting
• Medullary thyroid carcinoma – enlarged or painful thyroid nodule, persistent hoarseness
• Hypoglycemia – especially with concurrent insulin or sulfonylureas
• Renal dysfunction – sudden rise in serum creatinine, hematuria
• Gastro‑intestinal obstruction – ileus, urgent abdominal imaging

Monitoring

• Glycemic Control: HbA1c every 3 months; fasting glucose if on concomitant insulin.
• Weight & BMI: at baseline, 3, 6, 12 months (for obesity).
• Lipid Profile & Blood Pressure: annually or per protocol.
• Renal Function: serum creatinine, eGFR at baseline, 3 months, then annually.
• Pancreatic Enzymes: baseline amylase/lipase; repeat if clinical suspicion of pancreatitis.
• Thyroid Function: TSH and free T4 if clinical suspicion of thyroid disease.
• Adverse Events: patient diary or structured questioning at each visit.

Clinical Pearls

• “Knee‑Over‑Hip” Trick – inject the 3rd‑month titration of Saxenda actually requires a *sub‑cutaneous* injection, not intramuscular; a short 4‑mm needle reduces “dead space” errors.
• Delayed‑Feeding Caution – vial is stable at room temperature for 30 min; do not eat immediately after injection else absorption is delayed.
• Hitch‑Hiker Effect – patients who switch from rapid‑acting insulin glargine to liraglutide often lose 1.5–2 mmol/L in HbA1c within 4 weeks; a brief overlap may be advisable.
• Taste of the Taste – nausea often peaks during the first 2 weeks; patients who experience only mild symptoms tend to tolerate the medication long‑term.
• TTC vs. TTC – in a multicenter trial, TTC (Time‑to‑Target‑Control) was halved when liraglutide was used as the first add‑on rather than as a last‑resort therapy.
• Embedding the Data – keep a digital log of weight changes; a >5 % loss in body weight within 12 weeks predicts a >10 % loss at 1 year.

Key Takeaway: *Liraglutide* is a versatile GLP‑1 analog that offers glycemic control and weight reduction with a once‑daily, self‑administrated regimen, but vigilance for pancreatic, thyroid, and GI events is paramount.