What is a good scenario to start a Glucagon-like peptide-1 (GLP-1) receptor agonist (RA) in patients with type 2 diabetes?

Optimal Scenarios for Initiating GLP-1 Receptor Agonist Therapy

The best scenario to start a GLP-1 receptor agonist (GLP-1 RA) is in patients with type 2 diabetes who have established atherosclerotic cardiovascular disease (ASCVD) or multiple cardiovascular risk factors, regardless of baseline HbA1c. 1, 2

Primary Indications for GLP-1 RA Therapy

Cardiovascular Risk Reduction

• Established ASCVD: Patients with prior myocardial infarction, ischemic stroke, unstable angina, or who have undergone revascularization procedures 1, 2
• High CV Risk: Patients with multiple risk factors such as age ≥55 years with coronary/carotid/lower extremity artery stenosis >50%, left ventricular hypertrophy, eGFR <60 mL/min/1.73m², or albuminuria 2
• Documented CV Benefit: Several GLP-1 RAs (liraglutide, semaglutide, dulaglutide) have demonstrated significant reduction in major adverse cardiovascular events (MACE) 3, 4

Metabolic Considerations

• Need for Substantial Weight Loss: When weight reduction is a priority alongside glycemic control 1
• Inadequate Glycemic Control: When patients are not achieving HbA1c targets on metformin monotherapy 1
• Metformin Intolerance: Can be used as first-line therapy in patients who cannot tolerate metformin 5

Specific Clinical Scenarios for Initiation

1. At Diagnosis of ASCVD: When a patient with T2DM is newly diagnosed with cardiovascular disease 1
2. At Diagnosis of T2DM: In patients with pre-existing ASCVD 1
3. Hospital Discharge: Following admission for an ASCVD or diabetes-related event 1
4. When Avoiding Hypoglycemia is Critical: Due to their glucose-dependent mechanism of action, GLP-1 RAs have low intrinsic risk of hypoglycemia 6
5. Overweight/Obese Patients: When weight management is a priority alongside glycemic control 1

Dosing and Administration Considerations

• Start Low, Go Slow: Begin with the lowest dose and up-titrate gradually to mitigate gastrointestinal side effects 1
• Medication Adjustments:
  • Discontinue DPP-4 inhibitors before starting GLP-1 RA 1
  • If patient is on insulin or sulfonylureas, reduce doses (typically 20% for insulin, 50% for sulfonylureas) 1
• Administration Options: Consider patient preference for daily vs. weekly injections, or oral semaglutide 7

Contraindications and Cautions

Absolute Contraindications

• Personal or family history of medullary thyroid carcinoma 1, 3
• Multiple Endocrine Neoplasia syndrome type 2 (MEN2) 1, 3
• History of serious hypersensitivity to the drug 1

Use with Caution

• History of pancreatitis 1, 3
• Severe renal impairment (for certain GLP-1 RAs) 1
• Diabetic retinopathy (particularly with semaglutide) 1, 3
• Gastroparesis or active gallbladder disease 1

Monitoring After Initiation

• More frequent blood glucose monitoring for first 4 weeks of therapy 1
• Appropriate eye examinations if not done within past 12 months 1
• Monitor for gastrointestinal side effects (nausea, vomiting, diarrhea) 3

Clinical Pitfalls to Avoid

• Not Discontinuing DPP-4 Inhibitors: These medications work through similar mechanisms and should not be used together 1
• Failing to Adjust Insulin/Sulfonylurea Doses: Can lead to hypoglycemia 1
• Starting at Full Dose: Increases risk of gastrointestinal side effects and may lead to discontinuation 1
• Overlooking Retinopathy Screening: Particularly important with semaglutide due to potential worsening of diabetic retinopathy with rapid glucose reduction 1, 3

By following these guidelines, clinicians can appropriately identify patients who would benefit most from GLP-1 RA therapy while minimizing risks and optimizing outcomes.