Switching between GLP-1s: what the labels and trials support, and what nobody has studied

People switch GLP-1s for four reasons: the first one stopped working well enough, the side effects were too much, the supply or the price changed, or a newer drug looked better. Whatever the reason, they arrive at the same gap in the documentation. None of the four labels says anything about starting one of these drugs in someone already on another. This guide sets out what the trials do show, how the gap is bridged in practice, and what to settle with a prescriber before the switch.

What the labels say

Section 2 of each label describes how to start the drug from nothing: Wegovy at 0.25 mg, Zepbound at 2.5 mg, Ozempic at 0.25 mg, Mounjaro at 2.5 mg, each with its escalation table. None of them has a "patients switching from another GLP-1 receptor agonist" paragraph. None states an equivalent dose to any other product. The drug interaction sections list no interaction between GLP-1 agonists because the situation of taking two at once was not studied and is not intended.

So a switch is off the map of the label, and the two questions it raises, what dose to start the new drug at and whether to leave a gap, are answered by the prescriber's judgement rather than by a table.

What the trials show

Semaglutide versus tirzepatide for obesity: SURMOUNT-5. Aronne and colleagues (NEJM 2025, PubMed 40353578) randomised 751 adults with obesity or overweight and without diabetes to tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks. Mean weight change was minus 20.2 percent with tirzepatide and minus 13.7 percent with semaglutide. This is the only head-to-head trial of the two drugs at their weight-management doses, and it is why "switching up" to tirzepatide is the commonest switch people ask about.

In type 2 diabetes: SURPASS-2. Frias and colleagues (NEJM 2021, PubMed 34170647) compared tirzepatide 5, 10 and 15 mg with semaglutide 1 mg over 40 weeks in people with type 2 diabetes. Tirzepatide produced greater reductions in HbA1c and body weight at all three doses. Note the comparator dose: 1 mg semaglutide, not the 2 mg Ozempic maximum or the 2.4 mg Wegovy dose. The trial is often quoted without that caveat.

Semaglutide versus liraglutide: STEP 8. Rubino and colleagues (JAMA 2022, PubMed 35015037) showed weekly semaglutide 2.4 mg produced greater weight loss than daily liraglutide 3 mg over 68 weeks, which is the evidence behind switching from an older daily GLP-1 to a weekly one.

What none of them did. No trial switched participants from one drug to the other mid-course and measured what happened. The trials tell you how each drug performs from a standing start in a fresh population. They do not tell you what a person who has already lost 12 percent on semaglutide will lose after moving to tirzepatide, and the expectation that the full SURMOUNT-5 difference will be added on top is not supported by anything.

The starting-dose question

This is the decision the label leaves open, and it is where prescribers differ.

The conservative reading is that the Zepbound label's starting dose is 2.5 mg for 4 weeks, for everyone, because the escalation schedule exists to reduce GI adverse reactions and a person who has never had tirzepatide has never had tirzepatide. The Wegovy label's starting dose is 0.25 mg on the same logic.

The practical counter-argument is that a person who has tolerated a high dose of one GLP-1 for months has adapted to the class effects on gastric emptying and appetite, and that starting at the lowest dose means weeks of under-treatment and probable regain. Some prescribers therefore start a switcher at the second step (5 mg tirzepatide, 0.5 mg semaglutide) or occasionally higher. The labels do not endorse this; it is off-label judgement, and it should be made explicitly, not by default.

Two things are true whichever way the decision goes. The switch should never be to the maximum dose of the new drug. And the escalation rules of the new label, at least 4 weeks per step, apply from wherever you start.

The gap question

Both drugs have half-lives of days (about a week for semaglutide, about 5 to 6 days for tirzepatide, per their labels), so under a weekly schedule the old drug is still in circulation when the new one is first injected regardless of what you do. Starting the new drug on the day the old one was due, with no dose of the old drug that week, is the usual approach and keeps you within a single weekly rhythm. Taking both in the same week is not on any label and is the thing to avoid. A deliberate wash-out of several weeks is not required by any label and mainly guarantees regain.

Same molecule, different brand

Ozempic to Wegovy, or Mounjaro to Zepbound, is not a change of drug. The molecules are identical; the labels differ in indication (type 2 diabetes versus weight management, plus Wegovy's cardiovascular and MASH indications and Zepbound's sleep apnoea indication), maximum dose (Ozempic 2 mg versus Wegovy 2.4 mg or higher), pen device and escalation table. Prescribers commonly continue at the same milligram dose because the drug has not changed; the labels do not describe the transition either way. Insurance is usually the real reason for this switch, and the insurance guide covers why the indication on the prescription matters.

Brand to compounded, and back

Compounded semaglutide and tirzepatide are not FDA approved and are not interchangeable with the brand products. The FDA's page on its concerns with compounded GLP-1s describes products containing different salt forms, products at concentrations that differ from the brand strengths, and dosing errors during transitions. Three consequences for a switch:

The dose is written in milligrams either way, but the compounded vial's concentration determines the volume, and the brand pen's fixed doses (2.5, 5, 7.5, 10, 12.5, 15 mg for Zepbound) may not match the compounded strengths you were on. Confirm the milligram dose with the prescriber and run the volume through the dose unit converter.

A compounded product's strength is what the pharmacy's certificate of analysis says it is, which may not be exactly what the label says; a switch to brand can therefore feel like a change of dose even at the same nominal milligrams. Report that rather than adjusting.

Going from brand to compounded, the first vial is the highest-risk moment for a units-versus-millilitres error. The calculator site's five checks exist for that injection. FormBlends describes what its pharmacies dispense on its semaglutide and tirzepatide pages, and its tirzepatide introduction is the main-site starting point for people considering that drug.

Before the first new injection: settle these

Why you are switching, in one sentence, so that success can be judged against it. The starting dose and the escalation plan for the new drug, in writing. The day of the first new injection relative to the last old one. What happens to tolerability options (delay, hold, step down; see the dose escalation guide) if the new drug is rougher than the old. Whether the new product needs a new prior authorisation. For tirzepatide, the oral contraceptive warning (a barrier method for 4 weeks after starting and after each increase; see the pregnancy guide), which did not apply on semaglutide and catches people out. What the new pen or vial looks like and how it differs from the old one, using the pen and vial guide. The prescriber checklist has all of these as questions.

What to expect afterwards

The GI adverse reactions cluster during escalation on every label, so a switch is a return to escalation and to escalation-week side effects, even for someone who had been comfortable for months. Weight change in the first weeks reflects the transition as much as the drug. Judge the switch at the maintenance dose, after the number of weeks the new label's schedule requires to get there, not at week three.