What is the recommended dosage for Glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide (Victoza) or semaglutide (Ozempic)?

GLP-1 Receptor Agonist Dosing

For type 2 diabetes, initiate semaglutide at 0.25 mg subcutaneously once weekly for 4 weeks, then escalate to 0.5 mg weekly, with optional increase to 1 mg weekly if needed; for liraglutide, start at 0.6 mg daily for 1 week, then increase weekly by 0.6 mg increments to a maintenance dose of 1.2-1.8 mg daily. 1, 2

Semaglutide (Ozempic) Dosing Protocol

Initial Titration:

• Start at 0.25 mg subcutaneously once weekly for 4 weeks (this dose is for gastrointestinal tolerability only, not glycemic control) 2
• After 4 weeks, increase to 0.5 mg once weekly 2
• If additional glycemic control is needed after at least 4 weeks on 0.5 mg, increase to 1 mg once weekly (maximum dose) 2

Administration Details:

• Inject once weekly on the same day each week, at any time of day, with or without meals 2
• Rotate injection sites (abdomen, thigh, or upper arm) 2
• If a dose is missed, administer within 5 days; if more than 5 days have passed, skip and resume regular schedule 2

Liraglutide (Victoza) Dosing Protocol

Initial Titration for Type 2 Diabetes:

• Start at 0.6 mg subcutaneously once daily for 1 week (to minimize gastrointestinal symptoms) 1
• After 1 week, increase to 1.2 mg once daily 1
• If additional glycemic control is required after at least 1 week, increase to 1.8 mg once daily (maximum dose) 1

Administration Details:

• Inject once daily at any time of day, independently of meals 1
• Rotate injection sites within abdomen, thigh, or upper arm 1
• If more than 3 days have elapsed since last dose, reinitiate at 0.6 mg daily and retitrate 1

Obesity Management Dosing (Higher Doses)

For obesity or overweight with weight-related comorbidities, liraglutide requires higher dosing than diabetes management:

• Start at 0.6 mg daily for 7 days 3
• Increase by 0.6 mg weekly (1.2 mg, 1.8 mg, 2.4 mg) until reaching maintenance dose of 3.0 mg daily after 4 weeks 3

For semaglutide in obesity:

• Start at 0.25 mg weekly for 4 weeks 3
• Escalate through 0.5 mg, 1.0 mg, and 1.7 mg weekly every 4 weeks at each dose 3
• Reach maintenance dose of 2.4 mg weekly after 16 weeks 3

Critical Implementation Principles

Gradual Titration is Essential:

• Slow dose escalation over 4-week intervals (semaglutide) or weekly intervals (liraglutide) minimizes gastrointestinal adverse effects, particularly nausea and vomiting 3, 4
• Nausea occurs in 40% of liraglutide patients vs 14.8% with placebo; vomiting in 16% vs 4.3% 3
• Clinical judgment allows adjusting titration schedules based on individual tolerance 3

Missed Dose Management:

• If 2 consecutive doses are missed, resume at same dose if previously well-tolerated, otherwise consider lowering 3
• If 3 or more consecutive doses are missed, restart the full titration schedule 3
• Some patients achieve adequate response at submaximal doses and can continue long-term 3

Renal Considerations:

• No dose adjustment required for semaglutide, liraglutide, or dulaglutide in renal impairment, even with eGFR as low as 15 mL/min/1.73 m² 4
• Exenatide is the exception: use caution with CrCl 30-50 mL/min and avoid once-weekly formulation if CrCl <30 mL/min 4

Drug Interactions and Combination Therapy

Concomitant Medications:

• Do not combine GLP-1 receptor agonists with other GLP-1 agonists or DPP-4 inhibitors 3
• When using with insulin or sulfonylureas, reduce doses of these agents and monitor for hypoglycemia 3
• GLP-1 agonists delay gastric emptying, potentially affecting absorption of oral medications requiring rapid onset 3
• When combining with insulin, administer as separate injections in different sites (never mix) 1, 2

Cardiovascular Disease Considerations

For patients with established cardiovascular disease or multiple risk factors, prioritize semaglutide, liraglutide, or dulaglutide, which have proven cardiovascular benefits. 4

Safety Monitoring and Contraindications

Absolute Contraindications:

• Personal or family history of medullary thyroid carcinoma (MTC) 2
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 2
• Known hypersensitivity to the medication 2

Use with Caution:

• History of pancreatitis (consider alternative therapies) 3, 4
• Monitor for symptoms of thyroid tumors (neck mass, dysphagia, dyspnea, persistent hoarseness) 2

Common Adverse Effects:

• Gastrointestinal symptoms (nausea, vomiting, diarrhea) are dose-dependent and more frequent with short-acting agents 3
• Heart rate increases by approximately 7.5 bpm with liraglutide 5
• Acute pancreatitis occurs in <0.1% of patients 3

Perioperative Considerations

Emerging evidence suggests GLP-1 agonists delay gastric emptying and may increase aspiration risk under anesthesia, even with prolonged fasting. 3 This delayed gastric emptying persists despite standard fasting protocols, with case reports documenting regurgitation after 18-20 hours of fasting 3.