What are the essential medications for a patient with type 2 diabetes using Glucagon-like peptide-1 (GLP-1) receptor agonists?

Essential Medications When Using GLP-1 Receptor Agonists

Metformin as Foundational Therapy

Metformin should be the baseline therapy in all patients with type 2 diabetes using GLP-1 receptor agonists, unless contraindicated. 1

• Metformin remains first-line therapy and should be continued when adding GLP-1 receptor agonists for patients not meeting glycemic targets 1
• The combination of metformin with GLP-1 receptor agonists is recommended as add-on therapy before considering insulin 2
• Metformin is contraindicated in patients with renal insufficiency or severe liver disease, in which case GLP-1 receptor agonists can be used as monotherapy 3

Cardiovascular Protection Medications

For patients with established atherosclerotic cardiovascular disease (ASCVD), continue or initiate evidence-based cardiovascular medications alongside GLP-1 receptor agonists. 1

• Antiplatelet therapy (aspirin or P2Y12 inhibitors) should be maintained in patients with prior myocardial infarction, stroke, or revascularization 1
• Statins are essential for lipid management in patients with ASCVD or diabetes with additional cardiovascular risk factors 1
• ACE inhibitors or ARBs should be used for blood pressure control and renal protection, particularly in patients with albuminuria or eGFR <60 mL/min/1.73m² 1
• Beta-blockers should be continued in patients with heart failure with reduced ejection fraction or post-myocardial infarction 1

SGLT2 Inhibitors for Specific Comorbidities

Add SGLT2 inhibitors to GLP-1 receptor agonists in patients with heart failure (especially HFrEF) or chronic kidney disease. 1

• For patients with heart failure with reduced ejection fraction (EF <45%), SGLT2 inhibitors provide superior benefit for reducing heart failure hospitalization compared to GLP-1 receptor agonists alone 1
• In patients with CKD (eGFR 30-60 mL/min/1.73m² or UACR >30 mg/g, particularly >300 mg/g), SGLT2 inhibitors should be added to prevent CKD progression 1
• The combination of GLP-1 receptor agonists and SGLT2 inhibitors is safe and provides complementary benefits: GLP-1 receptor agonists reduce MACE while SGLT2 inhibitors reduce heart failure hospitalization 1

Insulin Dose Adjustment Protocol

When adding GLP-1 receptor agonists to existing insulin therapy, reduce basal insulin dose by approximately 20% if HbA1c is ≤8% to minimize hypoglycemia risk. 2

• GLP-1 receptor agonists combined with basal insulin provide additional HbA1c reduction with weight loss rather than weight gain 2
• When adding basal insulin to existing GLP-1 receptor agonist therapy, start with low-dose basal insulin and titrate slowly to target fasting plasma glucose 2
• The combination produces similar or greater HbA1c reduction compared to adding meal-time insulin, with reduced hypoglycemia risk 2

Sulfonylurea and Insulin Secretagogue Management

Reduce or discontinue sulfonylureas when initiating GLP-1 receptor agonists to prevent hypoglycemia. 4

• GLP-1 receptor agonists have minimal hypoglycemia risk as monotherapy due to glucose-dependent insulin secretion 5, 2
• The hypoglycemia risk increases significantly when combined with insulin secretagogues (sulfonylureas, meglitinides) 5
• Consider dose reduction of sulfonylureas by 50% or discontinuation when starting GLP-1 receptor agonists 4

Medications to Avoid or Use with Caution

Do not use GLP-1 receptor agonists in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. 5, 4, 6, 7, 8

• This is an absolute contraindication per FDA labeling for all GLP-1 receptor agonists 6, 7, 8
• Use caution in patients with history of pancreatitis; consider alternative antidiabetic therapies 6, 8
• Exenatide and lixisenatide are contraindicated in severe renal impairment (eGFR <30 mL/min), while liraglutide and semaglutide should be used with caution 4

Antihypertensive Medications

Continue or optimize blood pressure medications, targeting <130/80 mmHg in patients with diabetes and cardiovascular disease. 1

• ACE inhibitors or ARBs are preferred first-line agents for blood pressure control in diabetes with albuminuria 1
• Diuretics may be needed for volume management, particularly in patients with heart failure 1

Antiemetic Considerations

Have antiemetic medications available during GLP-1 receptor agonist initiation for managing gastrointestinal side effects. 4

• Nausea and vomiting are common during initial treatment but typically diminish over time 4
• Start with low doses and titrate slowly to minimize gastrointestinal effects 2, 4
• Shorter-acting agents may have more pronounced gastrointestinal symptoms 4

Special Populations: Pediatric Patients

In pediatric patients (≥10 years) with type 2 diabetes, metformin should be first-line therapy, with GLP-1 receptor agonists added for inadequate glycemic control. 1

• Liraglutide, semaglutide, and dulaglutide are FDA-approved for pediatric patients aged 10 years and older 1, 7, 8
• Insulin should be initiated if presenting with ketoacidosis, marked ketosis, random glucose ≥250 mg/dL, or HbA1c ≥8.5% 1
• Metformin should be added after resolution of ketosis or ketoacidosis 1

Critical Perioperative Management

Inform anesthesiologists about GLP-1 receptor agonist use before any surgical procedures due to delayed gastric emptying and aspiration risk. 2

• GLP-1 receptor agonists slow gastric emptying, which has led to reports of pulmonary aspiration during general anesthesia even after prolonged fasting 2
• Consider holding GLP-1 receptor agonists before elective surgery based on institutional protocols 2

Monitoring Requirements

Monitor for signs of pancreatitis, retinopathy progression (especially with semaglutide), and thyroid nodules during GLP-1 receptor agonist therapy. 4

• Discontinue GLP-1 receptor agonists if pancreatitis is suspected 4
• Monitor for retinopathy complications with semaglutide, especially with rapid glucose reduction 4
• Regular monitoring of renal function, particularly when combining with other nephrotoxic medications 4