What is the role of GLP-1 (Glucagon-like peptide-1) patches, such as semaglutide (Ozempic) or dulaglutide (Trulicity), in the treatment of a patient with type 2 diabetes mellitus (T2DM) who has not achieved adequate glycemic control with metformin or has established cardiovascular disease?

GLP-1 Receptor Agonists: Injectable Formulations Only—No Patches Currently Available

GLP-1 receptor agonists are not available as transdermal patches; they are administered exclusively via subcutaneous injection (weekly or daily) or oral tablet formulation. The question appears to conflate GLP-1 medications with patch delivery systems, which do not exist for this drug class 1, 2.

Available GLP-1 Formulations

Injectable Options (Subcutaneous)

• Once-weekly injections: Semaglutide (Ozempic), dulaglutide (Trulicity), and extended-release exenatide are administered subcutaneously once per week 3, 2
• Daily injections: Liraglutide (Victoza) requires daily subcutaneous administration 3, 1
• All injectable formulations use pre-filled pens for subcutaneous injection into the abdomen, thigh, or upper arm 2

Oral Option

• Oral semaglutide (Rybelsus): The only oral GLP-1 receptor agonist, approved in 2019, providing an alternative for patients unwilling to use injectable therapy 4, 5, 6
• Demonstrated noninferiority to placebo for cardiovascular outcomes (HR 0.79; 95% CI 0.57–1.11) 3

Clinical Indications for GLP-1 Receptor Agonists

Cardiovascular Disease Reduction

For patients with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, specific GLP-1 receptor agonists with proven cardiovascular benefit are strongly recommended 3, 1:

• Liraglutide: 13% reduction in major adverse cardiovascular events (HR 0.87; 95% CI 0.78–0.97) and 22% reduction in cardiovascular death (HR 0.78; 95% CI 0.66–0.93) 3, 1
• Semaglutide: 26% reduction in MACE (HR 0.74; 95% CI 0.58–0.95) 3, 1
• Dulaglutide: Demonstrated cardiovascular benefit with FDA approval for reducing major adverse cardiovascular events 3, 1

Chronic Kidney Disease

• GLP-1 receptor agonists with cardiovascular benefit (liraglutide, semaglutide, dulaglutide) are recommended for patients with type 2 diabetes and CKD who don't meet glycemic targets with metformin and/or SGLT2 inhibitors 3
• These agents can be used with eGFR as low as 15 mL/min/1.73 m² and retain glucose-lowering efficacy across all stages of kidney disease 3
• No dose adjustment required for semaglutide or dulaglutide in CKD 1

Dosing Protocols

Dulaglutide (Trulicity)

• Starting dose: 0.75 mg subcutaneously once weekly 2
• Titration: Increase to 1.5 mg weekly for additional glycemic control after at least 4 weeks 2
• Maximum dose: 4.5 mg once weekly, with 1.5 mg increments every 4 weeks as needed 2

Semaglutide (Ozempic)

• Starting dose: 0.25 mg subcutaneously weekly 1
• Titration: Increase to 0.5 mg or 1 mg weekly as tolerated 1

Liraglutide (Victoza)

• Starting dose: 0.6 mg subcutaneously daily 1
• Titration: Increase to 1.8 mg daily or maximally tolerated dose 1

Critical Safety Considerations

Absolute Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC) 1, 2
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1, 2
• Serious hypersensitivity reaction to the drug 1, 2
• Pregnancy or breastfeeding 1

Relative Contraindications and Cautions

• History of pancreatitis: Not studied in this population; consider alternative therapies 1, 2
• Severe gastroparesis or gastrointestinal disease: Not recommended 2
• Thyroid monitoring: Routine serum calcitonin or thyroid ultrasound is of uncertain value 2

Common Adverse Effects

• Nausea, vomiting, and diarrhea occur in 15-20% of patients but are typically transient and dose-dependent 3
• Management strategy: Start at low dose and titrate slowly to minimize gastrointestinal side effects 3, 1
• Heart rate increases by approximately 5 bpm but without associated adverse cardiovascular events 3

Comparative Effectiveness

GLP-1 RAs vs. SGLT2 Inhibitors

• Both classes reduce atherosclerotic cardiovascular events comparably in patients with established ASCVD 3
• SGLT2 inhibitors additionally reduce heart failure hospitalization and kidney disease progression 3
• Clinical decision: Use either class for cardiovascular risk reduction; whether combining both provides additive benefit remains unknown 3

Among GLP-1 Receptor Agonists

• Agents with proven cardiovascular benefit: Liraglutide, semaglutide, dulaglutide, and albiglutide (no longer available) 3
• Neutral cardiovascular effect: Lixisenatide and extended-release exenatide showed noninferiority but not superiority to placebo 3
• Weight loss: Semaglutide produces greater weight reduction (14.9% at 2.4 mg weekly) compared to other GLP-1 receptor agonists 3

Administration Pitfalls to Avoid

• Injection site rotation: Rotate between abdomen, thigh, and upper arm with each dose 2
• Concurrent insulin use: Administer as separate injections; never mix, though injections can be in the same body region if not adjacent 2
• Missed dose protocol: If >3 days until next scheduled dose, administer immediately; if <3 days, skip and resume regular schedule 2
• Visual inspection: Do not use if particulate matter or discoloration present 2