What is the subcutaneous semaglutide (Ozempic) titration schedule for an adult with type 2 diabetes?

Ozempic (Subcutaneous Semaglutide) Titration Schedule for Type 2 Diabetes

Start Ozempic at 0.25 mg subcutaneously once weekly for 4 weeks, then increase to 0.5 mg weekly for at least 4 weeks; if additional glycemic control is needed, escalate to 1.0 mg weekly after at least 4 weeks on the 0.5 mg dose, and for further intensification move to 2.0 mg weekly after at least 4 weeks at 1.0 mg. 1, 2

Standard Titration Protocol

• Week 0–4: Begin with 0.25 mg once weekly subcutaneously. This initial dose is designed to minimize gastrointestinal side effects (nausea, vomiting, diarrhea) rather than to provide therapeutic glycemic control. 1, 2

• Week 5–8 (minimum): Increase to 0.5 mg once weekly. This is the first maintenance dose and provides meaningful HbA1c reduction for many patients. 1, 2

• Week 9+ (if needed): After at least 4 weeks on 0.5 mg, escalate to 1.0 mg once weekly if additional glycemic control is required to reach individualized HbA1c targets (generally <7% for most adults). 1, 2

• Week 13+ (if needed): After at least 4 weeks on 1.0 mg, increase to 2.0 mg once weekly for patients requiring further intensification. This is the maximum approved dose for type 2 diabetes. 1

Administration Details

• Injection site: Administer subcutaneously in the abdomen, thigh, or upper arm. 1, 2

• Timing flexibility: Inject once weekly on the same day each week, at any time of day, with or without meals. 1, 2

• Day-of-week flexibility: The weekly injection day may be shifted provided at least 48 hours (2 days) separate consecutive doses. 3

Dose-Escalation Decision Points

• Assess glycemic response 12–16 weeks after reaching each new maintenance dose (0.5 mg, 1.0 mg, or 2.0 mg) by measuring HbA1c. 1

• Escalate the dose if HbA1c remains above target (typically >7%) after at least 4 weeks on the current dose. 1, 2

• Do not escalate if the patient experiences persistent severe gastrointestinal symptoms; instead, maintain the current dose for an additional 4 weeks to allow tolerance to develop. 2

Evidence for Higher-Dose Efficacy

• Semaglutide 2.0 mg versus 1.0 mg: In the SUSTAIN FORTE trial, patients on 2.0 mg weekly achieved an additional 0.23 percentage-point reduction in HbA1c (treatment difference –0.23%; 95% CI –0.36 to –0.11; p=0.0003) and an additional 0.93 kg weight loss (95% CI –1.68 to –0.18; p=0.015) compared with 1.0 mg weekly. 4

• Semaglutide 1.0 mg versus 0.5 mg: Phase 2 dose-finding studies demonstrated that 1.0 mg weekly produces greater HbA1c reduction than 0.5 mg weekly, supporting the stepwise titration approach. 5

Concomitant Medication Adjustments

• Reduce basal insulin by approximately 20% when starting Ozempic to lower hypoglycemia risk. 1, 3

• Discontinue sulfonylureas or cut the dose by 50% before initiating Ozempic to prevent additive hypoglycemia. 1, 3

• Stop all DPP-4 inhibitors (e.g., sitagliptin, linagliptin) before starting Ozempic, as concurrent use offers no additional glycemic benefit. 3

Missed-Dose Management

• Missed ≤5 days: Administer the dose as soon as possible, then resume the regular weekly schedule. 3, 2

• Missed >5 days: Skip the missed dose and administer the next dose on the originally scheduled day. 3, 2

• Two consecutive doses missed: Consider restarting at a lower dose to minimize gastrointestinal symptoms. 2

Renal Dosing

• No dose adjustment is required for any degree of renal impairment, including end-stage renal disease or dialysis. This makes semaglutide a preferred GLP-1 receptor agonist for patients with diabetic kidney disease. 1, 2

Absolute Contraindications

• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2) are absolute contraindications. Screen all patients before initiating therapy. 1, 3, 2

Common Pitfalls to Avoid

• Do not skip the 0.25 mg starting dose. Initiating at 0.5 mg or higher markedly increases gastrointestinal adverse events and discontinuation rates. 1

• Do not escalate doses faster than every 4 weeks. Rapid titration increases nausea, vomiting, and treatment discontinuation. 1, 5

• Do not assume oral semaglutide (Rybelsus) is interchangeable with subcutaneous Ozempic. They require different dosing schedules and are not bioequivalent. 2

• Do not delay dose escalation indefinitely. If HbA1c remains above target after 12–16 weeks on a given dose, escalate rather than waiting longer. 1