Every US-approved GLP-1 for weight management is approved as a combination. The drug is one half of it; the other half is written into the indication, in the same sentence, on all four labels: "in combination with a reduced-calorie diet and increased physical activity."
What that diet was is not a matter of opinion. It is written down in section 14 of each label, in the description of the trials the approval rests on. This page reads it out.
The phrase, on all four labels
Read 2026-09-20, from each product's own current label:
| Product | Molecule | The indication's opening words |
|---|---|---|
| WEGOVY | semaglutide | "indicated in combination with a reduced calorie diet and increased physical activity" |
| ZEPBOUND | tirzepatide | "indicated in combination with a reduced-calorie diet and increased physical activity" |
| SAXENDA | liraglutide | "indicated in combination with a reduced calorie diet and increased physical activity" |
| FOUNDAYO | orforglipron | "indicated in combination with a reduced-calorie diet and increased physical activity" |
Four products, two manufacturers, three molecules, more than a decade between the oldest approval and the newest — and the wording differs only in a hyphen.
The protocol, as the labels describe it
The great majority of these trials ran one specification, and the labels state it in nearly the same words.
"all patients received instruction for a reduced-calorie diet (approximately 500 kcal/day deficit) and increased physical activity counseling (recommended to a minimum of 150 min/week) that began with the first dose of study medication or placebo and continued throughout the trial" — WEGOVY label, describing Studies 2, 3, 5, 7, 8 and 9
ZEPBOUND's Studies 1 and 2 describe a "standard lifestyle intervention" with the same two numbers, and add a third element: patients "also received counseling on behavior modification strategies to adhere to diet and exercise recommendations." SAXENDA's three studies use the 500 kcal/day deficit and the 150 minutes as well.
Three points are easy to miss and change what the figures mean.
The programme starts on day one, alongside the first dose — not after some settling-in period. It continues for the whole trial, not for a lead-in. And the placebo group receives it too, which is what makes the placebo arms interpretable.
The intensive protocols, and the two trials that ran them
Two trials in this set prescribed something much harder, and both reported it precisely.
WEGOVY Study 4 put patients on an 8-week low-calorie diet at a total energy intake of 1,000 to 1,200 kcal/day, followed by 60 weeks at 1,200 to 1,800 kcal/day, with physical activity beginning at 100 minutes a week and increasing to 200.
ZEPBOUND Study 3 ran a 12-week intensive lifestyle lead-in before randomisation, in which "lifestyle instruction was delivered 8 times over 12 weeks by a dietician or dietician-equivalent, with all patients receiving instruction to exercise for at least 150 minutes per week and to reduce their caloric intake to approximately 1,200 kcal/day (females) or 1,500 kcal/day (males)."
SAXENDA Study 3 did something different again: a run-in of up to 12 weeks on 1,200 to 1,400 kcal/day, after which only the patients who had already lost at least 5% of their screening weight were randomised.
What the placebo arms show
Because placebo patients received the full lifestyle programme, the placebo column of each trial is a measurement of that programme without the drug.
| Trial | Lifestyle programme | Placebo arm at endpoint | Drug arm |
|---|---|---|---|
| WEGOVY Study 2 (68 w) | standard: 500 kcal deficit, 150 min/wk | −2.4% | −14.9% |
| WEGOVY Study 4 (68 w) | intensive: 1,000–1,200 then 1,200–1,800 kcal/day | −5.7% | −16.0% |
| ZEPBOUND Study 1 (72 w) | standard | −3.1% | −20.9% |
| FOUNDAYO Trial 1 (72 w) | standard | −2.1% | −11.1% |
| SAXENDA Study 1 (56 w) | standard | −3.0% | −7.4% |
The comparison inside the WEGOVY label is the one worth sitting with. Moving from the standard programme to the intensive one is associated with a 3.3-point improvement in the placebo group and a 1.1-point improvement in the drug group.
That is not a measurement of the diet's effect, and it should not be quoted as one. Studies 2 and 4 are separate trials with different enrolment; Study 4's patients had already completed an intensive lifestyle run-in, which selects for people who respond to one. What the contrast does establish is that the lifestyle arm of these protocols is large enough to matter and that it does not scale the same way in both groups — and that a figure like "−14.9%" is a figure for a drug plus a prescribed diet, never for a drug alone.
One more line in the placebo columns is easy to skip. In WEGOVY Study 4, 47.8% of placebo patients lost at least 5% of body weight and 27.1% lost at least 10% — on the diet and the activity programme, with no active drug.
The enrolment criterion nobody quotes
SURMOUNT-5, the only trial in the class that tested two of these products against each other, required participants to have "a history of at least 1 unsuccessful dietary effort to lose body weight."
The trials recruited people for whom dieting had already failed, and then prescribed them a diet. Both halves of that are in the record, and neither is usually stated next to the other.
What is not in any of these protocols
Nothing about protein targets, macronutrient splits, meal timing, fasting windows, restricted food categories or supplements appears in any trial description read for this page. The protocols specify a calorie figure and a minutes figure, and in ZEPBOUND's case behaviour-change counselling to keep to them.
The single food-related instruction anywhere in this set is not about diet at all. Its label directs that after the tablet is taken, food, other beverages and other oral medicines are delayed by at least 30 minutes — a rule about how much of the dose is absorbed, covered on the oral GLP-1 page.
What this page does not do
It does not give an eating plan, recommend a calorie figure, or say what anyone should eat. It reports what the trial protocols specified and what the resulting arms reported. Decisions about food alongside a prescribed medicine belong with a clinician and a dietitian.
The weight outcomes those protocols produced are ranked on the posted-results page; the muscle question that sits underneath the calorie deficit is on the muscle-loss page; and the escalation schedule that runs alongside the diet for the first four or five months is on the titration page.
Sources
- WEGOVY label (semaglutide), DailyMed SPL, version dated 2026-06-30, read 2026-09-20.
- ZEPBOUND label (tirzepatide), DailyMed SPL, version dated 2026-09-02, read 2026-09-20.
- SAXENDA label (liraglutide), DailyMed SPL, version dated 2026-06-15, read 2026-09-20.
- FOUNDAYO label (orforglipron), DailyMed SPL, version dated 2026-08-13, read 2026-09-20.
- SURMOUNT-5, NCT05822830, eligibility criteria, ClinicalTrials.gov, read 2026-09-20.