What is the recommended dosing regimen for Ozempic (semaglutide)?

Ozempic (Semaglutide) Dosing Regimen

Start Ozempic at 0.25 mg subcutaneously once weekly for 4 weeks, then increase to 0.5 mg weekly, with optional escalation to 1 mg weekly after at least 4 additional weeks if glycemic control remains inadequate. 1

Standard Dosing Protocol

The FDA-approved titration schedule follows a structured escalation to minimize gastrointestinal side effects while achieving therapeutic benefit:

• Weeks 1-4: 0.25 mg once weekly (initiation dose only—not effective for glycemic control) 1
• Week 5 onward: 0.5 mg once weekly (first therapeutic dose) 1
• Optional escalation: After at least 4 weeks on 0.5 mg, may increase to 1 mg once weekly if additional glycemic control is needed 1
• Maximum dose: 1 mg once weekly 1

Administration Guidelines

Timing and flexibility:

• Administer once weekly on the same day each week, at any time of day, with or without meals 1
• The day of weekly administration can be changed if at least 2 days (>48 hours) separate consecutive doses 1

Missed dose management:

• If missed, administer within 5 days of the scheduled dose 1
• If more than 5 days have passed, skip the missed dose and resume the regular schedule 1

Injection technique:

• Inject subcutaneously in the abdomen, thigh, or upper arm 1
• Rotate injection sites each week within the same body region 1
• When using with insulin, administer as separate injections—never mix products 1
• Injections may be in the same body region but not adjacent to each other 1

Gradual Titration Rationale

The slow dose escalation is critical for tolerability. For weight management indications specifically, guidelines recommend an even more gradual approach: starting at 0.25 mg weekly for 4 weeks, then 0.5 mg, 1.0 mg, 1.7 mg at 4-week intervals each, reaching the 2.4 mg maintenance dose after 16 weeks 2. However, for diabetes management (Ozempic), the maximum approved dose is 1 mg weekly 1.

Special Population Considerations

Renal impairment:

• No dosage adjustment required for any degree of renal impairment, including end-stage renal disease 2, 3

Hepatic impairment:

• No dosage adjustment required 2, 3

Critical Safety Warnings

Black box warning:

• Risk of thyroid C-cell tumors in rodents (human relevance undetermined) 2, 3
• Contraindicated in patients with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 3

Common adverse effects requiring monitoring:

• Gastrointestinal effects (nausea, vomiting, diarrhea) are dose-dependent and typically self-limited 2, 3
• May cause cholelithiasis and gallstone-related complications 2, 3
• Can cause elevated heart rate 2, 3
• Risk of severe constipation and small bowel obstruction/ileus 3

Drug interactions:

• Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors 2
• May delay gastric emptying, affecting absorption of oral medications with narrow therapeutic indices 3
• When used with insulin or sulfonylureas, reduce doses of these agents to prevent hypoglycemia 2, 3

Clinical Efficacy Context

Semaglutide demonstrates superior glycemic control compared to other agents, with HbA1c reductions of 1.5-1.9% after 30-56 weeks 4. In head-to-head comparisons, semaglutide 0.5-1.0 mg weekly achieved greater HbA1c reductions than insulin glargine (-1.21% and -1.64% vs -0.83%) with concurrent weight loss rather than weight gain 5.