Ozempic (Semaglutide) Dose Titration from 0.5 mg
Start with 0.25 mg once weekly for 4 weeks, then increase to 0.5 mg once weekly for at least 4 weeks; if additional glycemic control is needed after this period, escalate to 1.0 mg once weekly, and consider further titration to 2.0 mg weekly if the 1.0 mg dose proves insufficient. 1, 2, 3
Standard Titration Protocol
Initial Dose Escalation
- Begin at 0.25 mg subcutaneously once weekly for the first 4 weeks as the starter dose to minimize gastrointestinal side effects 1, 3
- Advance to 0.5 mg once weekly after completing the 4-week initiation period 1, 2
- Administer at any time of day, with or without meals, though taking with meals may improve gastrointestinal tolerability 1
Subsequent Dose Increases from 0.5 mg
After at least 4 weeks on the 0.5 mg maintenance dose, evaluate the need for further titration based on glycemic control: 1, 3
- If HbA1c remains above goal, increase to 1.0 mg once weekly 1, 4
- Allow another 4 weeks at 1.0 mg before considering additional escalation 3
- For patients requiring maximal glycemic control on 1.0 mg, escalate to 2.0 mg once weekly 5
Timing Considerations
- Steady-state plasma concentrations are achieved after 4-5 weeks at each dose level due to semaglutide's 7-day half-life 3
- Assess treatment response after 12 weeks on each maintenance dose before making decisions about further escalation 1
Dose-Specific Efficacy Data
0.5 mg Weekly Dose
- Produces HbA1c reductions of approximately 1.2-1.5% from baseline 4, 3
- Results in mean weight loss of 3.5-5 kg over 30 weeks 4
1.0 mg Weekly Dose
- Achieves HbA1c reductions of 1.6-1.9% from baseline 4, 3
- Generates mean weight loss of 5-6 kg over 30-40 weeks 4, 5
2.0 mg Weekly Dose
- Delivers HbA1c reduction of 2.2% from baseline, representing an additional 0.23 percentage point reduction compared to 1.0 mg 5
- Produces mean weight loss of 6.9 kg, approximately 0.9 kg more than the 1.0 mg dose 5
Critical Safety Monitoring
Gastrointestinal Side Effects
- Nausea occurs in 21-22% of patients and is typically transient, mild-to-moderate, and subsides with time 4, 6
- Gastrointestinal events are the most common reason for treatment discontinuation (4.5% of patients) 6
- The gradual dose escalation protocol specifically minimizes these adverse effects 3
Hypoglycemia Risk
- Severe or blood glucose-confirmed hypoglycemia occurs in only 4-6% of patients on semaglutide monotherapy or with metformin, significantly lower than insulin therapy (11%) 4
- Risk increases when combined with sulfonylureas or insulin 4
Renal Considerations
- No dose adjustments are required for any level of renal impairment, including eGFR <30 mL/min/1.73 m² 1
- This distinguishes semaglutide from several other GLP-1 receptor agonists that require renal dose adjustments 1
Common Pitfalls to Avoid
- Do not skip the 0.25 mg starter dose—this 4-week initiation period is essential for tolerability 1, 3
- Do not escalate doses more frequently than every 4 weeks—steady-state concentrations require this duration 3
- Do not discontinue prematurely for mild gastrointestinal symptoms—these typically resolve within weeks and are dose-dependent 6
- Do not use semaglutide for acute glycemic control—onset of action is gradual, with peak effects at steady state 3