GLP-1 dosing & titration reference

Why GLP-1s are titrated at all

Incretin agonists slow gastric emptying and act centrally on appetite signalling. Both effects are dose-dependent, and both are responsible for the adverse effects that cause patients to stop treatment — nausea, vomiting, early satiety, constipation. Starting doses for this class are deliberately sub-therapeutic: the opening tier exists to build tolerance, not to produce weight loss or glycaemic effect.

That reframes the escalation schedule. The interval between tiers is the active ingredient of the protocol. Compressing it to reach a target dose faster reliably produces the gastrointestinal burden that ends therapy, and a patient who discontinues at week six has received no benefit at all.

Semaglutide — weekly ladder

Semaglutide escalates through five tiers with four weeks at each, giving a 16-week runway before the maintenance dose is reached in week 17.

Two of the steps are not evenly spaced — 1 mg to 1.7 mg, then 1.7 mg to 2.4 mg — which is a common source of arithmetic error when staff assume a uniform increment. Read the tier off the table rather than deriving it.

Maintenance and dose reduction

Not every patient needs the top tier. Where response is adequate and tolerance is marginal, holding at 1 mg or 1.7 mg indefinitely is a legitimate maintenance strategy. Where a tier is poorly tolerated, stepping back one tier for four weeks and then re-attempting the increase is generally preferable to abandoning the agent.

Tirzepatide — weekly ladder

Tirzepatide uses uniform 2.5 mg increments, again on a four-week interval, with approved maintenance doses at 5, 10, and 15 mg depending on indication and response.

The 2.5 mg tier is an initiation dose only and is not intended as maintenance. Beyond 5 mg, escalation is driven by response and tolerance rather than by schedule — many patients remain at 5 mg or 10 mg permanently.

Missed doses and schedule changes

• Within about five days: administer as soon as it is noticed and resume the usual weekly day.
• Beyond five days: skip the missed dose entirely and give the next one on the regular day. Doubling up is not appropriate for a once-weekly agent.
• Two or more consecutive weeks missed: tolerance has decayed. Most prescribers restart at a lower tier and re-escalate rather than resuming the prior dose.
• Changing the dosing day: permitted provided at least 48 hours separate the two injections.

Converting a tier into what the patient actually draws

Approved-product labeling expresses doses in milligrams because the pen delivers a fixed volume at a fixed concentration. A compounded vial does not work that way: the pharmacy assigns the concentration when it reconstitutes or fills, so the same milligram dose is a different volume from one vial to the next.

Always convert from the concentration printed on the vial in front of you. Never carry a unit count across from a previous vial, a different pharmacy, or another patient — the dosage calculator does the conversion and shows the working.

Worked example: a 5 mg vial reconstituted with 2 mL yields 2.5 mg/mL. A 1 mg dose is therefore 0.4 mL, which reads as 40 units on a U-100 insulin syringe. Change the diluent volume to 1 mL and the identical 1 mg dose becomes 20 units. The dose did not change; the concentration did.

Counselling points that reduce discontinuation

• Set the expectation that nausea is dose-related, front-loaded, and usually settles within a tier.
• Smaller meals, stopping at first fullness, and reduced fat and alcohol intake meaningfully reduce symptoms.
• Hydration and fibre address the constipation that otherwise emerges around tier three.
• Agree in advance that a poorly tolerated tier will be held or stepped back — patients who expect this do not self-discontinue.
• Reinforce protein intake and resistance training; loss of lean mass is the predictable failure mode of rapid titration.

Cautions

This class carries a boxed warning for thyroid C-cell tumours in rodents and is contraindicated in personal or family history of medullary thyroid carcinoma and in MEN 2. Pancreatitis, gallbladder disease, diabetic retinopathy complications, and — with concurrent insulin or sulfonylureas — hypoglycaemia all require assessment before initiation and monitoring during escalation. Prescribing decisions belong to the treating clinician and to the current approved labeling, which supersedes anything on this page.

Common questions