STEP 7 deep dive: semaglutide 2.4 mg in East Asian adults (Mu 2024 Lancet)
Last verified 2026-05-28 · Phase 3a · Completed; primary results published Lancet Diabetes Endocrinol March 2024 · NCT04251156 ↗
STEP 7 (NCT04251156) is the registrational phase-3a trial of once-weekly semaglutide 2.4 mg in a predominantly East Asian adult population with overweight or obesity. Novo Nordisk randomized 375 participants at 23 hospitals and trial centers in China, Hong Kong, South Korea, and Brazil 2:1 to subcutaneous semaglutide 2.4 mg (n=249) or matching placebo (n=126), all layered on a reduced-calorie diet and increased physical activity, for 44 weeks. Randomization was stratified by type 2 diabetes diagnosis, since STEP 7 enrolled adults with or without T2D, a design choice distinct from STEP 1 through STEP 4. Results published by Mu and colleagues in The Lancet Diabetes & Endocrinology in March 2024 reported a mean body-weight change of -12.1% with semaglutide versus -3.6% with placebo, with 85% of the semaglutide arm achieving at least 5% weight loss versus 31% on placebo.
- Enrollment
- 375
- Duration
- 44 weeks of treatment with once-weekly subcutaneous injection, including the 16-week dose-escalation phase from 0.25 mg up to the 2.4 mg maintenance dose, plus standard safety follow-up
- Drug
- Semaglutide 2.4 mg (Wegovy)
- Population
- Adults aged 18 or older with overweight or obesity from a predominantly East Asian population enrolled across 23 sites in China, Hong Kong, South Korea, and Brazil. Participants were eligible with or without type 2 diabetes; randomization was stratified by T2D diagnosis. The Asian-population BMI thresholds used by the protocol identify obesity at lower absolute values than the WHO global cutoff. From Dec 8, 2020 to Aug 23, 2022, 448 were screened and 375 randomized (semaglutide 2.4 mg n=249; placebo n=126), with a 2:1 allocation ratio.
Primary endpoint
Coprimary: percentage change in mean body weight from baseline to week 44, and proportion of participants reaching at least 5% weight reduction at week 44 (full analysis set, treatment-policy estimand)
Treatment arm
Mean body-weight change -12.1% (SE 0.5); 5% threshold reached by 203/238 (85%)
Comparator
Mean body-weight change -3.6% (SE 0.7); 5% threshold reached by 36/116 (31%)
Treatment difference: Mean weight change: estimated treatment difference -8.5 percentage points (95% CI -10.2 to -6.8; p<0.0001). 5% threshold: odds ratio 13.1 (95% CI 7.4 to 23.1; p<0.0001).
The 44-week mean weight loss of 12.1% in a predominantly East Asian population sits below the 14.9% reported at 68 weeks in the multinational STEP 1 trial, but the 24-week-shorter treatment period accounts for most of the difference. The 8.5-percentage-point placebo-subtracted effect supported regulatory submissions in East Asian jurisdictions.
Secondary endpoints
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| Body-weight reduction at least 10% at week 44 The 10% threshold is the magnitude typically associated with improvements in OSA, NAFLD, and glycemic markers. | Semaglutide 2.4 mg: 66% | Placebo: 11% | Confirmatory secondary endpoint; p<0.0001 vs placebo |
| Body-weight reduction at least 15% at week 44 At 44 weeks, two in five East Asian participants reached the 15% threshold, a magnitude historically associated with bariatric surgery. | Semaglutide 2.4 mg: 42% | Placebo: 3% | Confirmatory secondary endpoint; p<0.0001 vs placebo |
| Waist-circumference change at week 44 (cm) Visceral-fat surrogate; magnitude meaningful in an East Asian population where central adiposity drives cardiometabolic risk at lower BMI values than in non-Asian populations. | Semaglutide 2.4 mg: -9.4 cm | Placebo: -3.1 cm | Estimated treatment difference -6.3 cm; p<0.0001 vs placebo |
| Systolic blood pressure change at week 44 (mmHg) Magnitude smaller than the -5.1 mmHg reported in STEP 1 at 68 weeks, consistent with the shorter treatment period. | Semaglutide 2.4 mg: -4.0 mmHg | Placebo: -0.7 mmHg | Estimated treatment difference -3.3 mmHg; nominal p<0.05 vs placebo |
| HbA1c change at week 44 (percentage points) Mixed population with and without type 2 diabetes; T2D subgroup showed a larger absolute HbA1c drop than the non-diabetic subgroup, as expected. | Semaglutide 2.4 mg: -0.5 percentage points | Placebo: -0.1 percentage points | Estimated treatment difference -0.4 percentage points; p<0.0001 vs placebo |
| Fasting plasma glucose change at week 44 (mg/dL) Direction and magnitude consistent with STEP 1 and STEP 2. | Semaglutide 2.4 mg: lower than placebo | Placebo: minimal change | Statistically significant favoring semaglutide; full numeric details in trial supplement |
| Total cholesterol change at week 44 (ratio to baseline) Reported in the prespecified lipid panel; magnitudes smaller than weight or waist changes. | Semaglutide 2.4 mg: modest reduction | Placebo: minimal change | Favors semaglutide; nominal significance reported |
| SF-36 v2 physical-functioning score change at week 44 Patient-reported outcome included in the prespecified secondary endpoint list. | Semaglutide 2.4 mg: improvement | Placebo: smaller improvement | Favors semaglutide; magnitudes reported in supplement |
Adverse events
| Event | Treatment rate | Comparator rate |
|---|---|---|
| Any adverse event Overall AE rate slightly elevated vs placebo, driven by gastrointestinal events. | 93% (231/249) | 86% (108/126) |
| Gastrointestinal disorders (any) Most common AE category; included nausea, diarrhea, vomiting, constipation. | 67% (168/249) | 36% (45/126) |
| Nausea Pattern matched STEP 1 — peaks during 16-week dose-escalation, then declines. | Reported as most-common single GI event | Lower than semaglutide arm |
| Diarrhea Typically transient. | Common GI event in semaglutide arm | Less common on placebo |
| Vomiting Most events mild-to-moderate. | More frequent than placebo | Less common |
| Serious adverse events No new safety signal identified versus the global STEP program. | Reported in both arms at low single-digit percentages | Similar order of magnitude |
| Discontinuation due to adverse events Consistent with the GI-discontinuation pattern observed across the STEP trials. | Single-digit percentage; predominantly GI-driven | Lower than semaglutide arm |
Subgroup analyses
- Chinese participants (prespecified subgroup, Gu 2025 Diabetes Obes Metab): Mean body-weight change -11.8% on semaglutide vs -3.5% on placebo; treatment difference -8.3 percentage points (95% CI -10.2 to -6.4; p<0.0001). 5% threshold reached by 85.4% vs 26.8% (odds ratio 16.1).
Subgroup of 300 Chinese participants (195 semaglutide; 105 placebo) within the overall STEP 7 population; effect size matched the full-trial result.
- Participants with type 2 diabetes: Mean body-weight change favored semaglutide; absolute HbA1c reduction larger than non-T2D subgroup
Stratification factor at randomization; consistent with the smaller absolute weight loss seen in T2D populations across the STEP program.
- Participants without type 2 diabetes: Larger absolute body-weight change versus placebo than the T2D subgroup
Pattern matches STEP 1 (non-diabetic) versus STEP 2 (T2D) comparison.
Clinical significance
STEP 7 closed the East Asian generalizability gap in the semaglutide obesity program. Before its publication, every pivotal STEP trial had been conducted in a predominantly non-Asian population, and clinicians in China, South Korea, Japan, and Hong Kong were left to extrapolate from STEP 1 and STEP 2 results to populations with lower baseline BMI, higher central adiposity at any given BMI, and different prevalence of cardiometabolic comorbidities at the Asian obesity threshold of BMI 28. The 8.5-percentage-point placebo-subtracted weight loss at 44 weeks, combined with the 13-fold odds of crossing the 5% threshold, fell within the same range as the multinational STEP trials and supported regional regulatory submissions. STEP 7 also functions as the semaglutide counterpart to SURMOUNT-CN for tirzepatide, allowing payers and providers to weigh the two agents using primary-source effect sizes from the same population.
Frequently asked questions
How does STEP 7 compare with STEP 1?
STEP 1 enrolled 1,961 predominantly non-Asian adults without type 2 diabetes and ran for 68 weeks with a 7-week off-drug extension. STEP 7 enrolled 375 predominantly East Asian adults with or without type 2 diabetes and ran for 44 weeks. STEP 1 reported a mean body-weight change of -14.9% versus -2.4% on placebo (treatment difference -12.4 percentage points); STEP 7 reported -12.1% versus -3.6% (treatment difference -8.5 percentage points). The shorter treatment period explains most of the difference in the semaglutide arm, and the inclusion of T2D participants explains part of the residual gap, since STEP 2 in T2D adults reported a smaller absolute weight loss than STEP 1 at the same dose.
Does the Chinese BMI threshold of 28 change how to read STEP 7?
Yes. Most East Asian guidelines, including those from the Chinese Diabetes Society and the Japan Society for the Study of Obesity, define obesity at BMI 28 or higher rather than the WHO threshold of 30, and overweight at BMI 24 to 27.9 rather than 25 to 29.9. STEP 7 used eligibility criteria aligned with the Asian-population thresholds, so a participant entering at BMI 29 would in many cases be classified as overweight in the United States but as obese under Chinese guidelines. The clinical implication is that the absolute kilogram losses reported in STEP 7 are smaller than the multinational STEP trials in part because the East Asian baseline weight was lower, even though the percentage losses are similar in direction and magnitude.
Did East Asian participants show smaller or larger effect sizes than the multinational STEP trials?
Effect sizes were directionally consistent and magnitudes were within the same range. The 8.5-percentage-point placebo-subtracted weight change at 44 weeks in STEP 7 sits between what was reported at the 28-week midpoint of STEP 1 and the full 68-week result, suggesting that the East Asian population responded along the same time-course as the multinational cohort. The 5% weight-loss threshold odds ratio of 13.1 was larger than the corresponding odds ratio in STEP 1, partly reflecting a lower placebo-arm response in STEP 7. The China-only prespecified subgroup analysis published in 2025 reported almost identical numbers to the full trial, supporting the generalizability of STEP 7 to Chinese patients specifically.
Was Wegovy approved in China based on STEP 7?
STEP 7 was the registrational trial that anchored Novo Nordisk's regulatory submissions for semaglutide 2.4 mg in East Asian jurisdictions, including China. The National Medical Products Administration of China approved semaglutide 2.4 mg (Wegovy) for chronic weight management in June 2024, with STEP 7 cited as the pivotal phase-3 evidence in the Chinese label. Pricing, distribution channels, and reimbursement decisions are made separately and have varied by province and payer.
How does STEP 7 compare with SURMOUNT-CN?
STEP 7 and SURMOUNT-CN are the semaglutide and tirzepatide counterpart phase-3 trials in East Asian populations. STEP 7 ran for 44 weeks and reported a 12.1% mean weight change on semaglutide 2.4 mg versus 3.6% on placebo (treatment difference -8.5 percentage points). SURMOUNT-CN ran for 52 weeks in 210 Chinese adults and reported a 17.5% mean weight change on tirzepatide 15 mg versus 2.3% on placebo (treatment difference -15.1 percentage points). The two trials used different durations, different BMI eligibility criteria, and different country mixes, so the head-to-head comparison should be made cautiously, but the magnitude gap between semaglutide and tirzepatide observed in STEP 7 versus SURMOUNT-CN mirrors the gap observed between STEP 1 and SURMOUNT-1 in the multinational populations.
Why did STEP 7 include participants with type 2 diabetes when STEP 1 did not?
STEP 1, STEP 3, and STEP 4 enrolled adults without type 2 diabetes; STEP 2 enrolled only adults with T2D. STEP 7 was designed to evaluate semaglutide 2.4 mg in a predominantly East Asian population that reflected real-world prescribing, where many candidates for weight-management therapy also have T2D or prediabetes. Randomization was stratified by T2D diagnosis to balance the arms, and prespecified subgroup analyses separated the effect sizes for T2D and non-T2D participants. The inclusion of both groups makes STEP 7 closer in design to a real-world East Asian obesity clinic population than STEP 1 or STEP 2 individually.
References
- 1.Mu Y, Bao X, Eliaschewitz FG, Hansen MR, Kim BT, Koroleva A, Ma RCW, Yang T, Zu N, Liu M; STEP 7 Study Group. Efficacy and safety of once weekly semaglutide 2·4 mg for weight management in a predominantly east Asian population with overweight or obesity (STEP 7): a double-blind, multicentre, randomised controlled trial. Lancet Diabetes Endocrinol. 2024. PMID: 38330988.
- 2.Gu W, Lu Y, Ye X, Yuan G, Liu D, Shen Z, Zu N, Mu Y. Efficacy and safety of once-weekly semaglutide 2.4 mg for weight management in participants from China: A prespecified analysis of the STEP 7 randomized clinical trial. Diabetes Obes Metab. 2025. PMID: 40069849.
- 3.U.S. National Library of Medicine. Research Study Investigating How Well Semaglutide Works in People From East Asia Suffering From Overweight or Obesity (STEP 7) — Study Record. ClinicalTrials.gov, NCT04251156. 2024. https://clinicaltrials.gov/study/NCT04251156