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STEP-3: Adding Intensive Behavioral Therapy

Last verified May 2026 · Phase 3a · Finished; published February 24, 2021 · NCT03611582 ↗

By Ruth Calder · Enforcement Editor
Editorially reviewed (not clinically reviewed). Not medical advice · How we verify contentLast reviewed

Sellers frequently bundle coaching into a monthly price, and readers reasonably ask whether it is worth anything or is a way to justify a fee. STEP-3 is the closest thing to an answer within this class. It is not a factorial design and cannot fully separate drug from therapy, but comparing its placebo arm against STEP-1's placebo arm gives a usable estimate of what structured support adds on its own — and comparing its drug arm against STEP-1's suggests the two are additive rather than redundant.

Enrollment
611
Duration
68 weeks on treatment with 30 counseling visits alongside it, then 7 weeks off the drug to week 75
Drug
Semaglutide 2.4 mg (Wegovy)
Population
Adults 18 and over with a BMI of 30 or more — or 27 or more if a weight-related condition came with it, meaning high blood pressure, abnormal cholesterol, sleep apnea or heart disease. Type 2 diabetes ruled people out, as did an HbA1c of 6.5% or above. Average starting weight 105.8 kg at a BMI of 38.0, average age 46, and 81% women. Run at 41 US sites between August 2018 and April 2020.

Primary endpoint

How much body weight came off over 68 weeks, with both groups getting the same intensive counseling

Treatment arm

−16.0%

Comparator

−5.7%

Treatment difference: Estimated treatment difference −10.3 percentage points (95% CI −12.0 to −8.6; P<0.001)

★ Because both arms got the identical 30-visit program with the same calorie and activity targets, the 10.3-point gap is the drug's contribution on top of the best behavioral support anyone offers. That is a cleaner read on what the injection itself does than any other trial in the program.

Secondary endpoints

EndpointTreatmentComparatorDifference
Lost at least 5% of body weight

★ Read the placebo column first: nearly half got there on counseling alone. This was not a sham comparison — the control arm was receiving real treatment and it worked.

86.6%47.6%P<0.001
Lost at least a tenth of body weight

Three quarters on the drug against roughly a quarter on the program alone.

75.3%27.0%P<0.001
Lost at least 15%

More than half crossed into the band that starts to overlap sleeve gastrectomy at one year.

55.8%13.2%P<0.001
Lost at least a fifth

⚠ Here the gap widens sharply — 35.7% against 3.7%. Counseling can take people a long way; it rarely takes them this far.

35.7%3.7%P<0.001
Weight lost in kilograms

Just under 17 kg, about 37 pounds, against 6.2 kg on the program alone.

−16.8 kg−6.2 kgEstimated treatment difference approximately −10.6 kg
Inches off the waist

Roughly 5.75 inches, more than double the placebo arm.

−14.6 cm−6.3 cmEstimated treatment difference −8.3 cm; P<0.001
Top blood-pressure number

Down about 4 points beyond the counseling-only group.

−5.6 mmHg−1.6 mmHgEstimated treatment difference −3.9 mmHg
Bottom blood-pressure number

A smaller shift, in the same direction.

−3.0 mmHg−0.8 mmHgEstimated treatment difference −2.2 mmHg
Three-month average blood sugar

⚠ Nobody here had diabetes, so this is movement inside the normal-to-prediabetic band rather than treatment of anything.

−0.51−0.27Estimated treatment difference approximately −0.24 percentage points
Triglycerides, a blood fat

Down over a fifth against about 6% on the program alone.

−22.5%−6.5%—

Adverse events

EventTreatment rateComparator rate
Any stomach or bowel problem

⚠ The highest rate anywhere in the STEP program — and note that 63.2% of the placebo group reported one too. Eating 1,000 to 1,200 calories a day produces a lot of what gets attributed to the drug.

82.8%63.2%
Nausea

Bunched into the 16 weeks while the dose was climbing, and largely gone by the maintenance phase.

58.2%22.1%
Constipation

Common in both arms, which again points at the diet as much as the drug.

36.9%24.5%
Diarrhea

About 36% against 22% on placebo.

36.1%22.1%
Vomiting

Roughly two and a half times the placebo rate.

27.3%10.8%
Gallbladder problems

Three times the placebo rate. This tracks how fast weight comes off rather than the drug specifically, and weight came off fast here.

4.9%1.5%
Serious adverse events of any kind

9.1% against 2.9% — a wider gap than most trials in this program showed.

9.1%2.9%
Quit over stomach and bowel problems

Counting every reason for stopping, 5.9% left the drug against 2.9% on placebo. ★ There were no deaths and not one case of acute pancreatitis.

3.4%0%

Clinical significance

This is the trial to cite when deciding whether a coaching add-on is worth paying for. The evidence says structured, intensive support helps — and 'intensive' here means 30 visits with a qualified clinician, which is not what most telehealth programs provide when they list coaching as an included feature. ⚠ Judge a seller's coaching against what STEP-3 actually delivered before treating this result as validation of it.

Who sells semaglutide, and for how much

This trial tested Semaglutide 2.4 mg (Wegovy). Across the 584 sellers on this register, 327 publish a standing monthly cash price for compounded semaglutide, from $59 a month, with a median of $175.

⛔ None of those sellers was in this trial. A compounded preparation is not the product studied here: no agency has reviewed that specific preparation for safety, effectiveness or manufacturing quality, and its concentration is set by whichever pharmacy filled it. The result above is the strongest evidence available for semaglutide and it was generated on something else. Every seller, with its price record.

Frequently Asked Questions

On its primary endpoint — How much body weight came off over 68 weeks, with both groups getting the same intensive counseling — the treatment arm recorded −16.0% against −5.7% for the comparator. Estimated treatment difference −10.3 percentage points (95% CI −12.0 to −8.6; P<0.001). ★ Because both arms got the identical 30-visit program with the same calorie and activity targets, the 10.3-point gap is the drug's contribution on top of the best behavioral support anyone offers. That is a cleaner read on what the injection itself does than any other trial in the program.
611 participants, over 68 weeks on treatment with 30 counseling visits alongside it, then 7 weeks off the drug to week 75. It was a Phase 3a trial, finished; published February 24, 2021. Registered as NCT03611582, which you can look up yourself rather than taking anyone's summary for it.
Adults 18 and over with a BMI of 30 or more — or 27 or more if a weight-related condition came with it, meaning high blood pressure, abnormal cholesterol, sleep apnea or heart disease. Type 2 diabetes ruled people out, as did an HbA1c of 6.5% or above. Average starting weight 105.8 kg at a BMI of 38.0, average age 46, and 81% women. Run at 41 US sites between August 2018 and April 2020. ⚠ A trial result describes the population it was measured in. If you differ from it materially — in age, in baseline weight, in whether you have diabetes — the number is context rather than a prediction.
The most commonly reported were any stomach or bowel problem (82.8% against 63.2% on comparator), nausea (58.2% against 22.1% on comparator), constipation (36.9% against 24.5% on comparator). ⚠ The highest rate anywhere in the STEP program — and note that 63.2% of the placebo group reported one too. Eating 1,000 to 1,200 calories a day produces a lot of what gets attributed to the drug. Rates come from this trial's population under its own dose-escalation schedule; a faster or slower titration changes what people experience.
Secondary endpoints included lost at least 5% of body weight (86.6% against 47.6%); lost at least a tenth of body weight (75.3% against 27.0%); lost at least 15% (55.8% against 13.2%). ⚠ Secondary endpoints are weaker evidence than the primary one — a trial is powered for its primary outcome, and the rest are read as supporting rather than as findings in their own right.
No, and this matters because the number gets used that way. STEP-3 tested Semaglutide 2.4 mg (Wegovy) — the FDA-approved product, made by its manufacturer under Good Manufacturing Practice, at the doses and schedule the protocol specified. A compounded preparation of semaglutide is a different product: no agency has reviewed that specific preparation for safety, effectiveness or manufacturing quality, and its concentration is set by whichever pharmacy filled it. ⛔ A seller quoting this trial's result beside a compounded price is quoting evidence that was generated on something they are not selling. That is not the same as saying compounded semaglutide does not work — it is saying nobody measured it here.
It cannot tell you that. A trial reports an average across a defined population under a fixed protocol, with monitoring and adherence support most people do not get. It is the best evidence available and it is still a distribution rather than a promise — some participants lost far more than the mean and some lost nothing. What it is genuinely good for is comparing options against each other, which is what the rest of this section is for.

References

  1. 1.Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O'Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT; STEP 3 Investigators. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021. PMID: 33625476.
  2. 2.U.S. National Library of Medicine. Research Study to Investigate How Well Semaglutide Works in People Suffering From Overweight or Obesity (STEP 3) — Study Results. ClinicalTrials.gov, NCT03611582. 2021. https://clinicaltrials.gov/study/NCT03611582
  3. 3.Wilding JPH, Batterham RL, Calanna S, et al.; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021. PMID: 33567185.
  4. 4.U.S. Food and Drug Administration. FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014 (Wegovy approval announcement). FDA News Release, June 4, 2021. 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014

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