Initial Dose of Semaglutide
Start semaglutide at 0.25 mg subcutaneously once weekly for the first 4 weeks, then increase to 0.5 mg weekly. 1, 2, 3
Dosing Protocol for Type 2 Diabetes
The standard titration schedule follows a structured escalation to minimize gastrointestinal side effects:
- Week 1-4: 0.25 mg subcutaneously once weekly 1, 2, 3
- Week 5 onward: 0.5 mg once weekly (standard maintenance dose for glycemic control) 1, 2
- Optional escalation: After at least 4 weeks at 0.5 mg, increase to 1.0 mg weekly if additional glycemic control is needed 1, 2
- Maximum dose for diabetes: 2.0 mg once weekly after at least 4 weeks at 1.0 mg 2, 4
The 0.25 mg starting dose is not therapeutic—it exists solely to reduce gastrointestinal adverse effects during initiation. 2, 3
Dosing Protocol for Obesity/Weight Management
For chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidities, continue escalation beyond diabetes dosing:
- Week 1-4: 0.25 mg weekly 2, 3
- Week 5-8: 0.5 mg weekly 2, 3
- Week 9-12: 1.0 mg weekly 2, 3
- Week 13-16: 1.7 mg weekly 2, 3
- Week 17 onward: 2.4 mg weekly (target maintenance dose) 2, 3
The 2.4 mg dose achieves approximately 9.6% total body weight loss compared to 3.4% with placebo. 2, 4
Administration Details
- Inject subcutaneously in the abdomen, thigh, or upper arm 2, 3
- Administer once weekly at any time of day, with or without meals 2, 4
- Maintain the same day each week for consistency 3
Key Clinical Considerations
No renal dose adjustments are required for any degree of kidney impairment, including end-stage renal disease. 1, 2, 4 This represents a significant advantage over other diabetes medications.
Gradual titration is mandatory, not optional—the 4-week intervals at each dose level minimize nausea (18% vs 7% with placebo) and other gastrointestinal symptoms. 2, 3 If gastrointestinal symptoms are severe, maintain the current dose for an additional 4 weeks before escalating. 3
Concomitant medication adjustments: Reduce insulin and sulfonylurea doses when initiating semaglutide to prevent hypoglycemia. 2 Never combine with other GLP-1 receptor agonists or DPP-4 inhibitors. 2, 3
Absolute Contraindications
- Personal or family history of medullary thyroid carcinoma 2, 3, 4
- Multiple endocrine neoplasia syndrome type 2 (MEN2) 2, 3, 4
- Pregnancy or lactation 2
- History of severe hypersensitivity to semaglutide 2
Missed Dose Management
- One missed dose: Resume at the next scheduled dose 3
- Two consecutive missed doses: Resume at current dose if previously well-tolerated; otherwise consider stepping back to lower dose 2, 3
- Three or more consecutive missed doses: Restart the entire titration schedule from 0.25 mg 2
Monitoring Requirements
Monitor for pancreatitis, gallbladder disease (symptomatic gallstones occurred in <0.05% of patients), and acute kidney injury when initiating or escalating doses. 2, 3 Watch for delayed gastric emptying effects on absorption of narrow therapeutic index medications like warfarin. 2
Treatment Duration
Semaglutide should be considered lifelong therapy—discontinuation results in significant weight regain (mean 11.6% of lost weight regained within 52 weeks after stopping). 1, 3 This is not a short-term intervention.