What are the usage, benefits, side effects, and contraindications of Semaglutide (Glucagon-like peptide-1 receptor agonist)?

Semaglutide: Usage, Benefits, Side Effects, and Contraindications

Semaglutide is a highly effective GLP-1 receptor agonist that provides significant weight loss (9.6-14.7% of total body weight) and glycemic control benefits, with the primary contraindication being a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2. 1

Usage and Dosing

Semaglutide is available in two formulations:

• Subcutaneous injection (Ozempic, Wegovy):

  • For type 2 diabetes (Ozempic): Starting at 0.25 mg weekly for 4 weeks, then 0.5 mg weekly, with potential increase to 1 mg weekly
  • For obesity management (Wegovy): 2.4 mg weekly after gradual dose escalation
  • Administration: Inject subcutaneously in abdomen, thigh, or upper arm 2

• Oral formulation:

  • Must be taken on an empty stomach with no more than 4 oz (120 mL) of water
  • Wait at least 30 minutes before eating, drinking, or taking other oral medications
  • Gradual dose escalation recommended 3

Primary Benefits

1. Weight Management:

   • Produces substantial weight loss of 9.6-14.7% of total body weight compared to 1.2-3.4% with placebo 1
   • More effective than other anti-obesity medications except tirzepatide 1

2. Glycemic Control:

   • Reduces HbA1c through glucose-dependent insulin stimulation and glucagon suppression
   • Delays gastric emptying, reducing postprandial glucose excursions 2
   • Reduces fasting glucose by 29 mg/dL (22%) and 2-hour postprandial glucose by 74 mg/dL (36%) 2

3. Cardiovascular Benefits:

   • Reduces major adverse cardiovascular events in patients with established cardiovascular disease 2
   • Provides cardioprotection through multiple mechanisms including reduced myocardial work, improved CV risk profile, and reduced atherogenesis 1

Side Effects

1. Gastrointestinal (most common):

   • Nausea, vomiting, diarrhea, constipation, abdominal pain
   • Usually mild to moderate and transient, occurring primarily during dose escalation 1, 4
   • Can be mitigated through gradual dose titration 1

2. Gallbladder-related issues:

   • Cholelithiasis (1.5% with 0.5 mg dose, 0.4% with 1 mg dose) 2
   • Increased risk of gallbladder disease 1, 4

3. Pancreatic concerns:

   • Pancreatitis has been reported in clinical trials, though causality not established
   • Discontinue if pancreatitis is suspected 1, 4

4. Other side effects:

   • Increased heart rate (2-3 beats per minute) 2
   • Fatigue, dysgeusia (altered taste), dizziness 2
   • Injection site reactions (with subcutaneous formulation) 2
   • Increased amylase (13%) and lipase (22%) 2

Contraindications

1. Absolute contraindications:

   • Personal or family history of medullary thyroid carcinoma 1, 3
   • Multiple endocrine neoplasia syndrome type 2 1, 3
   • Pregnancy or planned pregnancy 1
   • History of serious hypersensitivity reaction to semaglutide 1

2. Use with caution:

   • Patients with history of pancreatitis 2, 3
   • Patients with diabetic retinopathy (risk of complications due to rapid glucose reduction) 1, 4
   • Patients with severe renal impairment (use with caution, though no dose adjustment required) 1, 2
   • Patients with gastroparesis or prior gastric surgery 1

Drug Interactions

1. Insulin secretagogues (e.g., sulfonylureas) or insulin:

   • Increased risk of hypoglycemia
   • Consider dose reduction of these medications when adding semaglutide 2

2. Oral medications:

   • Semaglutide may delay gastric emptying, potentially affecting absorption
   • Monitor medications with narrow therapeutic index (e.g., warfarin)
   • No clinically significant interactions observed with metformin, warfarin, atorvastatin, or digoxin 5

Special Considerations

1. Monitoring recommendations:

   • Monitor for signs of pancreatitis (persistent severe abdominal pain)
   • Monitor for gallbladder disease (right upper quadrant pain)
   • In patients with diabetic retinopathy, monitor for worsening retinopathy, especially with rapid glucose improvement 4, 6

2. Practical administration tips:

   • Gradual dose escalation minimizes gastrointestinal side effects
   • For oral formulation, strict adherence to administration instructions is critical for proper absorption 3

Semaglutide represents a significant advancement in both diabetes and obesity management, offering substantial metabolic benefits with a generally favorable safety profile when used appropriately in the right patient population.