What is the recommended approach for using GLP-1 (Glucagon-like peptide-1) receptor agonist patches, such as exenatide (Exenatide) or dulaglutide (Dulaglutide), in patients with type 2 diabetes?

GLP-1 Receptor Agonists: There Are No Transdermal Patches Available

GLP-1 receptor agonists are not available as transdermal patches—all currently approved formulations are administered via subcutaneous injection (daily or weekly) or oral tablet. 1

Available Formulations and Routes of Administration

Injectable GLP-1 Receptor Agonists

Short-acting agents (subcutaneous injection):

• Exenatide: 5 mcg twice daily initially, increased to 10 mcg twice daily after 1 month, injected within 60 minutes before morning and evening meals 1, 2
• Lixisenatide: 10 mcg once daily initially, increased to 20 mcg once daily on day 15, taken within 60 minutes before the first meal 1
• Liraglutide: 0.6 mg once daily initially, titrated to 1.2-1.8 mg once daily after 1 week 1

Long-acting agents (subcutaneous injection, once weekly):

• Exenatide extended-release: 2 mg once weekly at any time of day 1
• Dulaglutide: 0.75 mg once weekly initially, can increase to 1.5 mg once weekly if additional glycemic control needed 1
• Semaglutide (subcutaneous): 0.25 mg once weekly for 4 weeks, then 0.5 mg once weekly, can increase to 1 mg once weekly after 4 weeks if needed 1

Oral Formulation

Semaglutide (oral): 3 mg once daily initially, taken at least 30 minutes before first food, fluid, or other oral medications with no more than 120 mL of plain water 1, 3

Clinical Selection Based on Patient Characteristics

For patients with BMI <30 kg/m²: Consider DPP-4 inhibitors or SGLT2 inhibitors as alternatives 1

For patients with BMI 30-35 kg/m²: GLP-1 receptor agonists or SGLT2 inhibitors are preferred 1

For patients with BMI >35 kg/m²: GLP-1 receptor agonists are the preferred choice 1

For patients with established cardiovascular disease: Long-acting GLP-1 receptor agonists with proven cardiovascular benefits (liraglutide, semaglutide, dulaglutide) should be prioritized 1, 3

For patients with chronic kidney disease (eGFR <60 mL/min/1.73 m² or albuminuria ≥30 mg/g): GLP-1 receptor agonists with proven cardiovascular benefits are preferred, especially if SGLT2 inhibitors are not tolerated 1

Renal Dosing Considerations

No dosage adjustment required:

• Liraglutide 1
• Dulaglutide 1
• Semaglutide (subcutaneous and oral) 1

Contraindicated or use with caution:

• Exenatide: Not recommended for CrCl <30 mL/min; use caution when initiating or escalating dose in CrCl 30-50 mL/min 1, 2
• Lixisenatide: Not recommended for CrCl <15 mL/min 1

Key Safety Considerations and Monitoring

Before initiating therapy:

• Discontinue any DPP-4 inhibitor 1
• Consider reducing sulfonylurea dose or discontinuing to prevent hypoglycemia 1
• Consider reducing total daily insulin dose by up to 20% if HbA1c is well-controlled at baseline 1

Contraindications (all GLP-1 receptor agonists):

• History of severe hypersensitivity to the drug 3, 2
• Personal or family history of medullary thyroid cancer 3
• Multiple endocrine neoplasia syndrome type 2 (MEN2) 3

Use with caution or avoid:

• Active pancreatitis or history of pancreatitis 3, 2
• Severe gastrointestinal disease (e.g., gastroparesis) 3, 2
• Active gallbladder disease 1, 3

Perioperative management:

• For patients taking GLP-1 receptor agonists for weight management: withhold for at least three half-lives before elective surgery due to risk of delayed gastric emptying and pulmonary aspiration 1, 2
• For patients with type 2 diabetes: discuss with endocrinologist, as prolonged cessation may worsen perioperative glycemic control 1

Common Pitfalls to Avoid

Gastrointestinal side effects: Nausea, vomiting, and diarrhea are common during initial treatment but typically diminish over time; start at the lowest dose and titrate slowly, recommend small portion sizes 1, 3

Hypoglycemia risk: When combined with insulin secretagogues or insulin, dose reduction of these agents is necessary to prevent hypoglycemia 1, 3, 2

Retinopathy monitoring: With semaglutide or dulaglutide, ensure appropriate eye examinations before starting therapy if not done within the last 12 months, particularly with rapid glucose reduction 1