GLP-1 Receptor Agonist Dosing
GLP-1 receptor agonists require gradual dose titration starting at low doses and increasing over 4-16 weeks to minimize gastrointestinal side effects, with specific dosing regimens varying by agent and indication (diabetes vs. weight loss).
Semaglutide Dosing
Subcutaneous Semaglutide for Type 2 Diabetes
- Start at 0.25 mg subcutaneously once weekly for 4 weeks 1, 2
- Increase to 0.5 mg once weekly after the initial 4 weeks 1
- Titrate to 1 mg once weekly (or maximally tolerated dose) for glycemic control 1, 2
- Maximum dose is 2 mg once weekly for diabetes 1
- The half-life is approximately 7 days, reaching steady state in 4-5 weeks 3
Subcutaneous Semaglutide for Weight Loss
- Start at 0.25 mg once weekly for 4 weeks 2
- Increase to 0.5 mg once weekly for 4 weeks 2
- Increase to 1.0 mg once weekly for 4 weeks 2
- Increase to 1.7 mg once weekly for 4 weeks 2
- Target maintenance dose is 2.4 mg once weekly after 16 weeks of titration 2
- This higher dose produces mean weight loss of 14.9% from baseline 1
Oral Semaglutide
- Start at 3 mg once daily for 30 days 1
- Increase to 7 mg once daily, then titrate to 14 mg once daily as tolerated 1, 4
- Oral semaglutide 14 mg daily demonstrates efficacy comparable to subcutaneous preparations 5, 4
Liraglutide Dosing
- Start at 0.6 mg subcutaneously daily 1
- Titrate slowly to 1.8 mg daily (or maximally tolerated dose) for diabetes 1
- For weight loss, titrate to 3.0 mg daily 6
- Liraglutide 1.8 mg daily is FDA-approved for cardiovascular risk reduction in patients with type 2 diabetes and established cardiovascular disease 1
Dulaglutide Dosing
- Start at 0.75 mg subcutaneously once weekly 1
- Titrate to 1.5 mg once weekly for cardiovascular benefit 1
- Higher doses of 3 mg and 4.5 mg once weekly are available for additional glycemic control 7
- Dulaglutide reaches steady state between 2-4 weeks with an elimination half-life of approximately 5 days 7
Exenatide and Lixisenatide Dosing
Exenatide Once Weekly
Lixisenatide
Critical Dosing Principles
Titration Strategy
- Slow dose escalation is essential to minimize nausea, vomiting, and other gastrointestinal adverse effects 1, 2
- Some patients achieve adequate glycemic control at submaximal doses and may continue long-term at lower doses 2
- Clinical judgment should guide adjustments based on individual response, tolerance, and adverse effects 2
Renal Dosing Adjustments
- No dose adjustment required for semaglutide, liraglutide, or dulaglutide in renal impairment, including end-stage renal disease 1
- Exenatide once weekly requires caution with creatinine clearance 30-59 mL/min and is not recommended below 30 mL/min 1
- Lixisenatide requires caution with creatinine clearance below 30 mL/min 1
Drug Interactions and Precautions
Combination Therapy Considerations
- Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors 2
- When combined with insulin or insulin secretagogues (sulfonylureas), reduce doses of these agents to minimize hypoglycemia risk 1, 2
- GLP-1 receptor agonists delay gastric emptying and may impair absorption of oral medications requiring rapid onset 2
Gastrointestinal Management
- Reduce meal size, limit alcohol and carbonated drinks, and avoid high-fat diets to minimize GI side effects 1
- Discontinue if pancreatitis is suspected and do not restart if confirmed 1
- Nausea and vomiting are dose-dependent and more frequent with short-acting agents 1, 5
Common Pitfalls
- Avoid rapid dose escalation, which significantly increases gastrointestinal intolerance 1, 2
- Monitor for diabetic retinopathy progression in high-risk patients (those with diabetes duration ≥10 years) on semaglutide 1, 6
- Provide sick-day planning and discontinue 3-4 days before scheduled surgery to avoid complications 1
- Weight regain occurs after discontinuation, indicating need for long-term therapy for sustained weight management 2