STEP-3: Adding Intensive Behavioral Therapy
Last verified May 2026 · Phase 3a · Finished; published February 24, 2021 · NCT03611582 ↗
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
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| 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 kg | Estimated 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 cm | Estimated 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 mmHg | Estimated treatment difference −3.9 mmHg |
| Bottom blood-pressure number A smaller shift, in the same direction. | −3.0 mmHg | −0.8 mmHg | Estimated 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 | −0.27 | Estimated 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
| Event | Treatment rate | Comparator 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 556 sellers on this register, 283 publish a standing monthly cash price for compounded semaglutide, from $79 a month, with a median of $174.
⛔ 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
References
- 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.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.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.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