Ozempic Dosage: Titration Steps, Pen Options, and Missed Dose Guidance

The Ozempic SmPC specifies a fixed titration schedule designed to minimise gastrointestinal side effects while achieving therapeutic semaglutide plasma concentrations.

Step 1: 0.25 mg once weekly for 4 weeks

This is not a therapeutic dose. It exists solely to allow GI adaptation. No clinically meaningful HbA1c reduction occurs at this dose.

Step 2: 0.5 mg once weekly (maintenance dose)

After 4 weeks at 0.25 mg, increase to 0.5 mg. This is the standard maintenance dose for most patients with type 2 diabetes. SUSTAIN trial data showed an average HbA1c reduction of 12 mmol/mol (1.

1%) at this dose.

Step 3: 1 mg once weekly (optional escalation)

If glycaemic targets are not met after at least 4 weeks at 0.5 mg, the dose can be increased to 1 mg. The 1 mg dose achieved HbA1c reductions of approximately 16 to 18 mmol/mol (1.5 to 1.

8%) in clinical trials.

• Do not skip the 0.25 mg step. Patients who start directly at 0.5 mg experience significantly higher rates of nausea and vomiting
• Each dose step should last a minimum of 4 weeks before escalation
• NICE NG 28 recommends reviewing HbA1c at 3 to 6 months after reaching maintenance dose to assess response

Ozempic is available in two pre-filled pen presentations in the UK, each containing semaglutide in a concentration of 1.34 mg/mL.

Pen 1 (red label): delivers 0.25 mg and 0.5 mg doses

This pen is used during the initiation phase and for patients maintained on 0.5 mg. It contains 1.5 mL of solution (2 mg total semaglutide) and provides either 4 doses of 0.

25 mg followed by further 0.5 mg doses, or a combination.

Pen 2 (blue label): delivers 1 mg doses

Used only for patients escalated to the 1 mg maintenance dose. Contains 3 mL of solution (4 mg total semaglutide).

Injection technique:

• Inject subcutaneously into the abdomen, thigh, or upper arm
• Rotate injection sites within the chosen region to reduce lipodystrophy risk
• The injection can be given at any time of day, independent of meals
• Choose a consistent day each week. If you wish to change the injection day, ensure at least 48 hours between doses
• Hold the pen against the skin for 6 seconds after the dose counter returns to zero to ensure full dose delivery
• Needles are not included with the pen. NovoFine or NovoTwist needles (30G or 32G) are compatible

Semaglutide has a half-life of approximately 7 days, which provides some flexibility around injection timing.

If you miss a dose:

• If fewer than 5 days have passed since the missed dose, inject as soon as you remember and continue your usual weekly schedule
• If 5 or more days have passed, skip the missed dose entirely and inject the next dose on your regular day
• Do not inject two doses in the same week to compensate for a missed dose

Changing your injection day:

You can change the day of the week you inject Ozempic provided there are at least 2 days (48 hours) between doses.

For example, if you normally inject on Monday, you could shift to Wednesday the following week, then continue on Wednesday thereafter.

Storage requirements:

• Unused pens: store in a refrigerator (2 to 8 degrees C). Do not freeze
• Pens in use: store below 30 degrees C or in a refrigerator. Use within 56 days of first use
• Protect from direct light. Keep the pen cap on when not in use
• If the solution appears cloudy, discoloured, or contains particles, do not use it

Patients who miss two or more consecutive doses should contact their prescriber. Restarting at a lower dose may be advisable to reduce the risk of GI side effects recurring.

The Ozempic SmPC provides specific guidance on dosing in populations that may require additional monitoring or caution.

Renal impairment:

No dose adjustment is required for mild, moderate, or severe renal impairment (eGFR down to 15 mL/min).

Ozempic is not recommended in end-stage renal disease (eGFR below 15 mL/min) due to lack of data. Dehydration from GI side effects can worsen renal function, so fluid intake monitoring is essential.

Hepatic impairment:

No dose adjustment is needed for mild or moderate hepatic impairment. Data in severe hepatic impairment are limited, and caution is advised.

Elderly patients (65 years and over):

No dose adjustment is required based on age alone.

However, NICE NG 28 recommends less stringent HbA1c targets (typically 58 mmol/mol rather than 48 mmol/mol) in frail elderly patients, which may affect the decision to escalate beyond 0.5 mg.

Pregnancy and breastfeeding:

Ozempic is contraindicated in pregnancy. Women of childbearing potential should use effective contraception.

Semaglutide should be discontinued at least 2 months before a planned pregnancy to allow drug washout (based on the 7-day half-life and 5 half-life clearance principle).

Animal studies showed embryotoxicity. There are no data on excretion in breast milk.

Patients may switch to Ozempic from other GLP-1 receptor agonists such as liraglutide (Victoza), dulaglutide (Trulicity), or exenatide (Bydureon/Byetta). The BNF does not mandate a washout period.

Practical switching guidance:

• From daily liraglutide (Victoza): stop liraglutide and start Ozempic 0.25 mg the next day. Begin the standard titration schedule. Patients previously tolerating liraglutide 1.8 mg often tolerate Ozempic titration well
• From weekly dulaglutide (Trulicity): start Ozempic 0.25 mg on the day the next dulaglutide dose would have been due
• From weekly exenatide ER (Bydureon): start Ozempic 0.25 mg on the day the next exenatide dose would have been due

Key considerations when switching:

• Do not skip the 0.25 mg titration step even if the patient was on a high dose of another GLP-1 agonist
• Monitor blood glucose more frequently during the first 4 weeks after switching
• GI side effects may recur during the transition, though they are often milder than with initial GLP-1 exposure
• If the patient was on a GLP-1 agonist combined with insulin, review the insulin dose at the point of switch. Semaglutide 1 mg typically provides greater HbA1c reduction than most other GLP-1 agents

NICE NG 28 supports switching between GLP-1 receptor agonists when the current agent is not achieving adequate glycaemic control or is poorly tolerated.

Regular clinical monitoring ensures Ozempic is both effective and safe over the long term. NICE NG 28 and the BNF outline the key parameters to track.

At initiation and each dose change:

• Body weight and BMI
• Review of GI symptoms and tolerability
• Blood glucose monitoring plan (frequency depends on concomitant medications and hypoglycaemia risk)

At 3 to 6 months after reaching maintenance dose:

• HbA1c: NICE recommends reviewing at 6 months. If HbA1c has not fallen by at least 11 mmol/mol (1.0%), consider dose escalation to 1 mg or reassess the treatment strategy
• Renal function (eGFR and urine albumin:creatinine ratio), particularly in patients with pre-existing CKD
• Lipid profile: semaglutide modestly improves total cholesterol and triglycerides

Annual reviews:

• Retinal screening: particularly relevant in the first 12 months if HbA1c has improved rapidly
• Foot examination and cardiovascular risk assessment (standard diabetes care)
• Review of injection technique and site rotation
• Assessment of whether the patient still meets criteria for continued GLP-1 therapy under NICE NG 28

Stopping criteria:

NICE previously recommended discontinuation if HbA1c did not improve by 11 mmol/mol at 6 months.

Current guidance is more flexible, considering weight loss and cardiovascular benefit alongside glycaemic outcomes. Discuss continuation at each annual review.