Semaglut

Approved Uses:

• Type 2 Diabetes Mellitus (T2DM):
  Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Can be used alone or in combination with other antidiabetic agents.
• Cardiovascular Risk Reduction:
  To reduce the risk of major adverse cardiovascular events (MACE) in adults with T2DM and established cardiovascular disease.

Clinically Accepted Off-Label Use:

• Obesity / Weight Management (non-diabetic):
  Used for chronic weight management in adults with a BMI ≥30 kg/m² or ≥27 kg/m² with at least one weight-related condition (e.g., hypertension, dyslipidemia).

Route of Administration:
• Oral (Rybelsus®)
• Subcutaneous (Ozempic®)

Oral Dosing (Adults with T2DM):

• Start with 3 mg once daily for 30 days
• Then increase to 7 mg once daily
• If needed, increase to 14 mg once daily after at least 30 days at 7 mg

Injection Dosing (Adults with T2DM):

• Initial: 0.25 mg subcutaneously once weekly for 4 weeks
• Increase to 0.5 mg once weekly for at least 4 weeks
• If further control is required, increase to 1 mg once weekly
• Maximum dose: 2 mg subcutaneously once weekly

Weight Loss (off-label use):

• Initiate at 0.25 mg/week and titrate up to 2.4 mg/week (typically under Wegovy® brand internationally)

Special Populations:

• Renal or Hepatic Impairment: No dose adjustment required, but use with caution
• Elderly: No dosage adjustment needed
• Pediatric Use: Injection approved in patients ≥12 years old (not oral)

Administration Instructions:

• Oral: Take on an empty stomach with water, at least 30 minutes before food or other medications
• Injection: Administer subcutaneously in the abdomen, thigh, or upper arm (rotate sites)

Semaglutide is a GLP-1 receptor agonist that mimics human glucagon-like peptide-1. It enhances glucose-dependent insulin secretion, suppresses inappropriate glucagon secretion, delays gastric emptying, and reduces appetite. These actions lead to improved glycemic control and weight loss in diabetic and obese patients.

• Absorption:
  • Oral: Low bioavailability (~0.4–1%)
  • SC: Slow absorption; peak in 1–3 days
• Distribution:
  Volume of distribution ~0.07 L/kg; highly protein-bound (>99%)
• Metabolism:
  Undergoes proteolytic degradation (not CYP-mediated)
• Elimination:
  Half-life ~165 hours (~1 week); eliminated via urine and feces as metabolites

• Pregnancy:
  Limited human data; animal studies show fetal harm. Discontinue at least 2 months before a planned pregnancy due to long half-life. Use only if benefits outweigh risks.
• Lactation:
  Unknown if excreted in breast milk. Avoid during breastfeeding or weigh benefits vs risks.

• Primary: Incretin Mimetic
• Subclass: GLP-1 Receptor Agonist
• Therapeutic Use: Antidiabetic Agent; Weight Reduction (off-label)

• Hypersensitivity to semaglutide or any excipients
• Personal or family history of medullary thyroid carcinoma (MTC)
• Patients with multiple endocrine neoplasia syndrome type 2 (MEN 2)

• Thyroid C-cell tumors: Risk observed in animal studies
• Pancreatitis: Discontinue if suspected or confirmed
• Diabetic retinopathy complications: Use caution in patients with history of retinopathy
• Hypoglycemia risk: Especially when combined with sulfonylureas or insulin
• Acute kidney injury: Monitor renal function if dehydration occurs
• GI symptoms: Can cause nausea, vomiting, diarrhea — monitor fluid/electrolyte status

Common:

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Appetite reduction
• Weight loss

Serious/Uncommon:

• Acute pancreatitis
• Diabetic retinopathy progression
• Gallbladder disease (e.g., cholelithiasis)
• Acute kidney injury
• Anaphylaxis or angioedema

• Insulin and Sulfonylureas: Increased risk of hypoglycemia
• Oral drugs with narrow therapeutic index (e.g., levothyroxine, warfarin): May affect absorption
• Gastrointestinal motility modifiers: May reduce oral absorption
• No CYP450 metabolism: Low interaction potential with CYP substrates

• ADA 2024 Recommendations:
  GLP-1 agonists like semaglutide preferred for overweight patients with T2DM and high CV risk
• Expanded Indication:
  Subcutaneous semaglutide (under Wegovy®) approved in many countries for obesity
• Ongoing trials:
  Exploring kidney protection and NASH (non-alcoholic steatohepatitis)

• Injection Pens (Unopened): Store in refrigerator (2°C–8°C). Do not freeze. Protect from light.
• Injection Pens (In-Use): May be stored at room temperature (≤30°C) for up to 56 days.
• Oral Tablets: Store below 30°C in original packaging. Protect from moisture.