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

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

Semaglutide is a 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

   • 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

   • To reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal MI, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease 1
   • Demonstrated cardiovascular benefits in the SUSTAIN-6 trial 2

3. Diabetic Kidney Disease Management

   • 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
   • No dosage adjustments required for renal impairment 2

Specific Patient Populations

• Patients with established cardiovascular disease: Preferred choice due to proven cardiovascular benefits 2
• Patients with obesity: Effective for weight management in conjunction with lifestyle modifications 3, 4
• Patients with high metabolic risk factors: Recommended for poorly controlled type 2 diabetes with obesity 2

Dosage and Administration

• Starting dose: 0.25 mg once weekly subcutaneously
• Titration: After 4 weeks, increase to 0.5 mg once weekly; if additional glycemic control is needed after at least 4 more weeks, can increase to 1 mg once weekly 1
• Administration: Can be administered at any time of day, with or without meals 1
• Injection site: Subcutaneously in the abdomen, thigh, or upper arm 1

Limitations of Use

• Has not been studied in patients with a history of pancreatitis; consider another antidiabetic therapy in these patients 1
• Not indicated for use in type 1 diabetes mellitus or treatment of diabetic ketoacidosis 1
• Contraindicated in patients with personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1

Important Safety Considerations

• Thyroid C-cell tumors: Contraindicated in patients with personal or family history of MTC or MEN 2 1
• Pancreatitis: Discontinue promptly if pancreatitis is suspected 1
• Diabetic retinopathy: Patients with history of diabetic retinopathy should be monitored 1
• Hypoglycemia: Consider lowering doses of insulin secretagogues or insulin when used in combination 1
• Gastrointestinal adverse effects: Most common side effects include nausea, vomiting, diarrhea, abdominal pain, and constipation 1
• Euglycemic DKA: Monitor for symptoms during illness, surgery, or periods of reduced oral intake 5

Cardiovascular Benefits

Semaglutide has demonstrated significant cardiovascular benefits in clinical trials:

• Reduction in major adverse cardiovascular events 2
• Reduction in hospitalization due to heart failure (76% reduction) 6
• Reduction in deaths due to cardiovascular causes (17% reduction) 6
• Reduction in non-fatal myocardial infarction (24% reduction) 6
• Reduction in coronary revascularization (24% reduction) 6

Pregnancy Considerations

• Discontinue semaglutide in women at least 2 months before a planned pregnancy due to the long washout period 1

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