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 if additional glycemic control is needed after at least 4 weeks on the 0.5 mg dose. 1

Standard Dosing Protocol

The FDA-approved titration schedule is designed to minimize gastrointestinal side effects while achieving therapeutic efficacy:

• Initiation phase: 0.25 mg subcutaneously once weekly for 4 weeks (this dose is for treatment initiation only and is not effective for glycemic control) 1
• Maintenance phase: Increase to 0.5 mg once weekly after the initial 4 weeks 1
• Optional escalation: If additional glycemic control is required, increase to 1 mg once weekly after at least 4 weeks on the 0.5 mg dose (maximum recommended dose is 1 mg weekly) 1

Administration Guidelines

Administer Ozempic once weekly on the same day each week, at any time of day, with or without meals. 1, 2

• Inject subcutaneously into the abdomen, thigh, or upper arm, rotating injection sites each week within the same body region 1
• The day of weekly administration can be changed if necessary, provided at least 2 days (>48 hours) elapse between doses 1
• If a dose is missed: Administer as soon as possible within 5 days; if more than 5 days have passed, skip the missed dose and resume the regular schedule 1

Special Population Considerations

No dose adjustments are required for renal or hepatic impairment, including end-stage renal disease. 3, 2

• Semaglutide undergoes proteolytic cleavage and does not require kidney-based dose modifications 3
• Monitor eGFR when initiating or escalating doses in patients with CKD who experience severe gastrointestinal reactions 3
• Limited data exist for severe CKD, but no dosage adjustment is necessary 3

Critical Safety Considerations

Ozempic is contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 1, 2

• A black box warning exists for thyroid C-cell tumors observed in rodents; human relevance is undetermined 1, 2
• Counsel patients about symptoms of thyroid tumors (neck mass, dysphagia, dyspnea, persistent hoarseness) 1

Common adverse effects are predominantly gastrointestinal and dose-related:

• Nausea, vomiting, diarrhea, and constipation are the most frequent side effects 3, 2
• The gradual titration schedule minimizes these effects 3
• Gastrointestinal adverse events led to treatment discontinuation in approximately 4.5% of patients in clinical trials 3

Drug Interactions and Combination Therapy

When using Ozempic with insulin or insulin secretagogues (sulfonylureas), reduce doses of these agents to minimize hypoglycemia risk. 3, 2

• Do not use semaglutide with other GLP-1 receptor agonists or DPP-4 inhibitors 3
• Semaglutide delays gastric emptying and may impact absorption of oral medications requiring rapid onset of action 3
• When co-administering with insulin, use separate injections in different sites (not adjacent to each other) 1

Peri-operative Management

For elective surgery, consider withholding Ozempic the week before procedures requiring general anesthesia due to delayed gastric emptying and aspiration risk. 3

• The American Society of Anesthesiologists recommends stopping weekly GLP-1 receptor agonists one week before elective procedures 3
• This recommendation balances the risk of pulmonary aspiration (OR 10.23 in elective surgery) against the adverse impact of drug cessation 3

Clinical Context for Cardiovascular Disease

For patients with type 2 diabetes and established cardiovascular disease, semaglutide is FDA-approved to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal MI, or non-fatal stroke). 3, 1

• The American College of Cardiology prioritizes GLP-1 receptor agonists with documented cardiovascular benefits, including semaglutide, as first-line therapy 3, 2
• Semaglutide demonstrated superior cardiovascular outcomes in the SELECT trial, even in patients with obesity without diabetes 4