What are the indications and usage for Semaglutide (GLP-1 receptor agonist)?

Indications and Usage for Semaglutide (GLP-1 Receptor Agonist)

Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease. 1

Primary Indications

1. Glycemic Control

   • Approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus 1
   • Can be used as first-line therapy with or without metformin in individuals with or at high risk for ASCVD, heart failure, or kidney disease 2

2. Cardiovascular Risk Reduction

   • Indicated to reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes mellitus and established cardiovascular disease 1
   • Demonstrated significant reduction in the primary composite outcome (MI, stroke, or cardiovascular death) in clinical trials 2

3. Diabetic Kidney Disease

   • Recommended for patients with type 2 diabetes and eGFR of 2 mL/min per 1.73 m² or lower or UACR of 30 mg/g or higher 2
   • Particularly beneficial for patients with existing or high risk of ASCVD or metabolic risk factors such as poorly controlled type 2 diabetes and obesity 2

Weight Management

While not explicitly mentioned in the FDA label provided, semaglutide at higher doses (2.4 mg once weekly) has been approved for chronic weight management in adults with obesity or overweight with at least one weight-related condition 3.

Dosage and Administration

• Start at 0.25 mg once weekly for 4 weeks
• Increase to 0.5 mg once weekly
• If additional glycemic control is needed after at least 4 weeks, increase to 1 mg once weekly 1
• Administer subcutaneously in the abdomen, thigh, or upper arm at any time of day, with or without meals 1

Important Limitations of Use

• Not indicated for use in type 1 diabetes mellitus
• Not indicated for treatment of diabetic ketoacidosis
• Has not been studied in patients with a history of pancreatitis; consider another antidiabetic therapy in these patients 1

Contraindications

• Personal or family history of medullary thyroid carcinoma
• Multiple Endocrine Neoplasia syndrome type 2
• Known hypersensitivity to semaglutide or any product components 1

Cardiovascular Benefits

Semaglutide has demonstrated significant cardiovascular benefits in clinical trials:

• Reduction in cardiovascular death, non-fatal MI, or non-fatal stroke 2
• 76% reduction in hospitalization due to heart failure
• 17% reduction in deaths due to cardiovascular causes
• 21% reduction in deaths from any cause
• 24% reduction in non-fatal myocardial infarction 4

Adverse Effects

The most common adverse reactions (≥5% of patients) include:

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Constipation 1

Special Considerations

• Renal Function: No dosage adjustment required for patients with renal impairment, but monitor renal function in patients reporting severe adverse gastrointestinal reactions 1
• Pregnancy: Discontinue semaglutide in women at least 2 months before a planned pregnancy due to the long washout period 1
• Risk of Euglycemic DKA: While the risk appears lower than with SGLT2 inhibitors, monitor for symptoms particularly during illness, surgery, or periods of reduced oral intake 5

Semaglutide represents a significant advancement in diabetes management, offering both glycemic control and cardiovascular protection for patients with type 2 diabetes.