Semaglutide Dosing & Pharmacology

Overview

Semaglutide is administered as a once-weekly subcutaneous injection with a standardized stepwise titration designed to minimize gastrointestinal adverse events. The pharmacokinetic profile supports weekly dosing through a long terminal half-life and consistent steady-state exposures. Both Ozempic and Wegovy share identical pharmacology; differences between products are in indication and packaging.

Standard titration schedule

• Weeks 1–4: 0.25 mg subcutaneously once weekly (initiation dose, not therapeutic — designed to limit GI side effects during introduction)
• Weeks 5–8: 0.5 mg once weekly
• Weeks 9–12: 1.0 mg once weekly
• Weeks 13–16: 1.7 mg once weekly
• Week 17 onward: 2.4 mg once weekly (maximum maintenance dose; Wegovy weight indication)

Many clinicians use slower titration, extending each step to six or eight weeks when GI tolerability is limiting. Patients may also maintain on intermediate doses (0.5 mg, 1.0 mg, 1.7 mg) long-term if response and tolerability are adequate.

Pharmacokinetic profile

Semaglutide has a terminal elimination half-life of approximately 5 days, supporting once-weekly dosing. Steady-state plasma concentrations are reached after approximately 4 weeks of weekly administration. The molecule is a synthetic peptide containing a C-20 fatty diacid moiety that binds albumin, prolonging circulation time. Absolute bioavailability after subcutaneous injection is approximately 80%. Time to maximum concentration (Tmax) is approximately 24 hours. Semaglutide is metabolized by proteolytic cleavage of the peptide backbone; renal and hepatic impairment have limited effects on overall exposure but warrant clinical caution.

Dose selection guidance

Dose selection is individualized based on glycemic and weight response, tolerability, and treatment goals. In the SUSTAIN program for type 2 diabetes, mean HbA1c reductions on semaglutide 0.5 mg and 1.0 mg averaged approximately -1.4% to -1.8% from baseline, with greater reduction at the higher dose. In STEP-1 for obesity (NEJM 2021, PMID 33567185), mean change in body weight on semaglutide 2.4 mg was -14.9% vs -2.4% on placebo at 68 weeks. Higher doses generally provide more benefit but with greater GI adverse events; titration speed and final dose should be tailored to each patient.

Missed dose handling

• If a dose is missed and the next scheduled dose is more than 3 days (72 hours) away: administer the missed dose as soon as possible, then resume the regular weekly schedule.
• If less than 3 days remain before the next scheduled dose: skip the missed dose and resume on the regular schedule.
• The day of weekly administration may be changed when needed, provided the gap between doses is at least 3 days.

Storage and handling

Unopened pens and vials should be refrigerated at 2°C to 8°C (36°F to 46°F). Once in use or out of refrigeration, semaglutide may be stored at room temperature (up to 30°C / 86°F) for up to 21 days, after which any unused medication should be discarded. Do not freeze. Protect from light. Discard the pen if frozen or exposed to temperatures above 30°C.

Frequently asked questions

Why is the starting dose 0.25 mg if it's not a maintenance dose?

The 0.25 mg starting dose is designed to allow the body to acclimate to GLP-1 receptor stimulation, reducing the severity of initial gastrointestinal adverse events. It does not produce maximum clinical benefit but is essential for safe titration.

Can I take semaglutide twice a week to titrate faster?

No. Semaglutide is dosed weekly. Twice-weekly dosing has not been studied, is not labeled, and would substantially increase adverse event risk without expected clinical benefit.

Is there a maximum effective dose?

15 mg is the FDA-labeled maximum maintenance dose. Some patients respond well to lower doses long-term and do not need to escalate to 2.4 mg. Trial data do not support routine dosing above 15 mg.