Semaglutide 2.5 mg/ml Starting Dose
Start semaglutide at 0.25 mg subcutaneously once weekly for the first 4 weeks, regardless of whether the indication is type 2 diabetes or weight management. 1, 2
Standard Initiation Protocol
The 0.25 mg weekly dose serves as a tolerance-building phase rather than a therapeutic dose—its primary purpose is to allow gastrointestinal adaptation to the medication. 1
Dose Escalation Schedule
After the initial 4-week period at 0.25 mg weekly:
- Week 5 onwards: Increase to 0.5 mg subcutaneously once weekly 3, 1
- Week 9 onwards (if needed): May escalate to 1.0 mg once weekly after at least 4 weeks on the 0.5 mg dose if additional glycemic control is required 3, 1
- Week 13 onwards (if needed): Can further increase to 2.0 mg once weekly for diabetes management 3
- For weight management: Target dose is 2.4 mg once weekly, reached after 16 weeks of gradual titration 3, 1
Administration Guidelines
- Timing: Administer once weekly on the same day each week, at any time of day, with or without meals 2
- Route: Subcutaneous injection 3
- Consistency: Maintaining the same weekly schedule improves adherence 2
Special Population Considerations
- Renal impairment: No dose adjustment required, even in end-stage renal disease 1, 2
- Hepatic impairment: Use with caution in severe hepatic impairment due to limited data, but no specific dose adjustment recommended 1
- Elderly patients: No age-based dose adjustment necessary 1
Critical Safety Considerations
Contraindications include personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2), based on rodent studies showing thyroid C-cell tumors. 3, 2
Common adverse effects are predominantly gastrointestinal—nausea (21-22% of patients), vomiting, diarrhea, and constipation—which are minimized by the gradual dose escalation schedule. 3, 4
Monitor for:
- Acute gallbladder disease and cholelithiasis 3
- Pancreatitis (use caution in patients with history) 3
- Hypoglycemia when combined with insulin or sulfonylureas—dose reduction of these agents may be necessary 3, 1
- Suicidal ideation and behavior 3
Practical Pitfalls to Avoid
- Do not skip the 0.25 mg starting dose: Jumping directly to higher doses significantly increases gastrointestinal side effects and treatment discontinuation 1
- Missed doses: If 3 or more consecutive doses are missed, restart the titration schedule from 0.25 mg 1
- Drug interactions: Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors 1
- Oral medication timing: Semaglutide delays gastric emptying, which may impact absorption of oral medications requiring rapid onset 1