What the trials asked participants to do besides inject

Every headline number from the GLP-1 trials was produced by people who were also on a structured lifestyle programme. The papers say so in the methods section, which almost nobody reads. It changes how the numbers should be used.

STEP 1 (semaglutide 2.4 mg)

All 1,961 participants, in both arms, received lifestyle intervention: individual counselling sessions every 4 weeks to help them adhere to a reduced-calorie diet (500 kcal per day below their estimated energy requirement) and increased physical activity (150 minutes per week encouraged), with diet and activity recorded daily in a diary or app and reviewed at the sessions (PubMed 33567185). The placebo arm, on that programme alone, lost 2.4 percent at 68 weeks.

SURMOUNT-1 (tirzepatide 5, 10, 15 mg)

Same structure. All 2,539 participants received regular lifestyle counselling delivered by a dietitian or qualified health professional, to a 500 kcal per day deficit and at least 150 minutes of physical activity per week (PubMed 35658024). The placebo arm lost 3.1 percent at 72 weeks.

STEP 4 and SURMOUNT-4 (the withdrawal trials)

Counselling continued through both the run-in and the randomised period, in both arms (PubMed 33755728; PubMed 38078870). This is worth sitting with: the people who regained 6.9 and 14.0 percent after switching to placebo were still receiving diet and activity counselling while they regained it. Counselling as delivered in these trials did not prevent regain. See maintenance after stopping.

Why it matters for reading the curves

1. The drug effect is the difference between arms, not the treatment arm alone. In STEP 1, -14.9 minus -2.4 gives about 12.4 points attributable to the drug on top of the programme. In SURMOUNT-1 at 15 mg, -20.9 minus -3.1 gives about 17.8 points.
2. The treatment-arm number includes the programme. Someone on the drug with no dietary structure, no activity change and no follow-up is not in the population the curve describes. They may do as well; the trial does not say.
3. Monthly contact is itself an intervention. Regular weighing, a diary, and a professional looking at it every four weeks changes behaviour independent of any advice given.

What "500 kcal below requirement" meant in practice

Requirement was estimated, typically from an equation like Mifflin-St Jeor with an activity factor, and 500 kcal subtracted. For a 100 kg, 170 cm, 45-year-old woman at the bottom of the sedentary activity band, that is roughly 2,350 kcal estimated and 1,850 kcal targeted; see energy needs for the arithmetic. It was a target discussed at visits, not an enforced intake, and adherence was recorded rather than verified. Nobody knows precisely what participants ate. What is known is that a GLP-1 makes such a deficit far easier to hold, which is most of how it works.

If you are on therapy without the programme

Many people on a GLP-1 today, especially through telehealth, get the prescription and little else. That does not doom the result; it means the trial curve is a looser reference. The pieces of the programme that are easy to reproduce:

• A weekly weight, logged, with a monthly look at the trend (how to weigh yourself).
• A protein target, because on a GLP-1 the risk is eating too little of it, not too much food overall (protein targets).
• 150 minutes a week of moderate activity plus two or three strength sessions (aerobic activity; resistance training).
• Someone who reviews it with you. A registered dietitian, a pharmacist, or the prescriber at follow-up visits.

The FormBlends GLP-1 program describes what follow-up FormBlends provides; note that FormBlends dispenses compounded products, which are not FDA approved and were not the products used in these trials.