TABLE 1.
STEP trials 1‐5 and 8: study designs and participant population baseline demographics and clinical characteristics 16 , 38 , 39 , 40 , 41 , 42 , 43
| STEP 1 16 , 38 | STEP 2 16 , 39 | STEP 3 16 , 40 | STEP 4 16 , 41 | STEP 5 16 , 42 | STEP 8 43 | |
|---|---|---|---|---|---|---|
| Weight management | Weight management in type 2 diabetes | Weight management with intensive behavioural therapy | Sustained weight management | Two‐year weight management | Semaglutide vs. liraglutide | |
| N | 1961 | 1210 | 611 | 902 enrolled; 803 randomized | 304 | 338 |
| Participants | Adults with BMI ≥30, or BMI ≥27 with ≥1 comorbidity, and without diabetes a | Adults with BMI ≥27 and type 2 diabetes, with HbA1c 7.0%‐10.0% b | Adults with BMI ≥30, or BMI ≥27 with ≥1 comorbidity, and without diabetes a | Adults with BMI ≥30, or BMI ≥27 with ≥1 comorbidity, and without diabetes a | Adults with BMI ≥30, or BMI ≥27 with ≥1 comorbidity, and without diabetes a | Adults with BMI ≥30, or BMI ≥27 with ≥1 comorbidity, and without diabetes a |
| Treatment arms and randomization ratios |
Semaglutide 2.4 mg vs. placebo 2:1 ratio |
Semaglutide 2.4 mg Semaglutide 1.0 mg Placebo 1:1:1 ratio |
Semaglutide 2.4 mg vs. placebo 2:1 ratio |
All receive semaglutide for 20 weeks (dose escalation) Then semaglutide 2.4 mg vs. placebo 2:1 ratio |
Semaglutide 2.4 mg vs. placebo 1:1 ratio |
Semaglutide 2.4 mg vs. placebo vs. liraglutide 3.0 mg vs. placebo 3:1:3:1 ratio |
| Duration of study | 68 weeks of treatment | 68 weeks | 68 weeks | 68 weeks (randomization into two arms at week 20) | 104 weeks | 68 weeks |
| Primary endpoints |
% change in body weight ≥5% weight loss |
% change in body weight ≥5% weight loss (semaglutide 2.4 mg vs. placebo) |
% change in body weight ≥5% weight loss |
% change in body weight |
% change in body weight ≥5% weight loss |
% change in body weight |
| Confirmatory secondary endpoints (in hierarchical testing order) |
≥10% weight loss ≥15% weight loss Change in: Waist circumference Systolic blood pressure Physical functioning (SF‐36 and IWQOL‐lite‐CT) |
≥10% weight loss ≥15% weight loss Change in: Waist circumference % change in body weight (semaglutide 2.4 vs. 1.0 mg) HbA1c Systolic blood pressure Physical functioning (SF‐36 and IWQOL‐lite‐CT) |
≥10% weight loss ≥15% weight loss Change in: Waist circumference Systolic blood pressure Physical functioning (SF‐36) |
Change in: Waist circumference Systolic blood pressure Physical functioning (SF‐36) |
≥10% weight loss ≥15% weight loss Change in: Waist circumference Systolic blood pressure |
≥10% weight loss ≥15% weight loss ≥20% weight loss |
| Background treatment | Lifestyle intervention Reduced‐calorie diet (500 kcal/day deficit relative to estimated energy expenditure) and increased physical activity (150 min/week) | Lifestyle intervention Reduced‐calorie diet (500 kcal/day deficit relative to estimated energy expenditure) and increased physical activity (150 min/week) | Intensive behavioural therapy Low‐calorie diet (1000‐1200 kcal/day) as meal replacements for first 8 weeks post‐randomization then a hypocaloric diet (1200‐1800 kcal/day) of conventional food for remainder of the 68 weeks. Participants were prescribed 100 min/week of physical activity at randomization, increasing by 25 min every 4 weeks, to reach 200 min/week 30 individual intensive behavioural therapy visits with a registered dietitian | Lifestyle intervention Reduced‐calorie diet (500 kcal/day deficit relative to estimated energy expenditure) and increased physical activity (150 min/week) | Lifestyle intervention Reduced‐calorie diet (500 kcal/day deficit relative to estimated energy expenditure) and increased physical activity (150 min/week) | Lifestyle intervention Reduced‐calorie diet (500 kcal/day deficit relative to estimated energy expenditure) and increased physical activity (150 min/week) |
| Sex, female, n (%) | 1453 (74.1) | 616 (50.9) | 495 (81.0) | 634 (79.0) | 236 (77.4) | Sema/lira/placebo: 102 (81.0)/97 (76.4)/66 (77.6) |
| Age, years; mean (SD) | 46 (13) | 55 (11) | 46 (13) | 46 (12) | 47 (11) | Sema/lira/placebo: 48 (14)/49 (13)/51 (12) |
| Race, n (%) | ||||||
| White | 1472 (75.1) | 751 (62.1) | 465 (76.1) | 672 (83.7) | 283 (93.1) | Sema/lira/placebo: 94 (74.6)/95 (74.8)/60 (70.6) |
| Black/African American | 111 (5.7) | 100 (8.3) | 116 (19.0) | 104 (13.0) | 12 (3.9) | Sema/lira/placebo: 25 (19.8)/20 (15.7)/19 (22.4) |
| Asian | 261 (13.3) | 317 (26.2) | 11 (1.8) | 19 (2.4) | 2 (0.7) | Sema/lira/placebo: 4 (3.2)/6 (4.7)/3 (3.5) |
| Other c | 117 (6.0) | 42 (3.5) | 19 (3.1) | 8 (1.0) | 7 (2.3) | Sema/lira/placebo: 3 (2.4)/6 (4.7)/3 (3.5) |
| Mean body weight, kg | 105.3 | 99.8 | 105.8 | 107.2 | 106.0 | 104.5 |
| HbA1c, %; mean (SD) | 5.7 (0.32) | 8.1 (0.8) | 5.7 (0.3) | 5.7 (0.3) | 5.7 (0.3) | Sema/lira/placebo: 5.5 (0.3)/5.5 (0.3)/5.6 (0.4) |
| BMI, kg/m2; mean (SD) | 37.9 (6.7) | 35.7 (6.3) | 38.0 (6.7) | 38.4 (6.9) | 38.5 (6.9) | Sema/lira/placebo: 37.0 (7.4)/37.2 (6.4)/38.8 (6.5) |
| Waist circumference, cm; mean (SD) | 114.7 (14.7) | 114.6 (14.1) | 113.0 (15.5) | 115.3 (15.5) | 115.7 (14.8) | Sema/lira/placebo: 111.8 (16.3)/113.5 (15.0)/115.4 (15.1) |
| Blood pressure, mmHg; mean (SD) | ||||||
| Systolic | 126.5 (14.3) | 130.0 (13.5) | 124.4 (14.8) | 127 (14) | 125.5 (14.5) | Sema/lira/placebo: 125 (14)/126 (16)/123 (14) |
| Diastolic | 80.3 (9.6) | 79.8 (9.0) | 80.5 (9.7) | 81 (10) | 80.1 (9.4) | Sema/lira/placebo: 81 (9)/81 (10)/79 (9) |
| Prediabetes d | 885 (43.6) | NA | 305 (49.9) | 408 (45.3) | 141 (46.4) | Sema/lira/placebo: 43 (34.1)/45 (35.4)/34 (40.0) |
| Number of comorbidities at screening, n (%) e | ||||||
| 0 | 491 (25.0) | 0 | 148 (24.2) | 214 (26.7) | NA | Sema/lira/placebo: 32 (25.4)/25 (19.7)/16 (18.8) |
| 1 | 524 (26.7) | 124 (10.2) | 146 (23.9) | 238 (29.6) | Sema/lira/placebo: 31 (24.6)/29 (22.8)/17 (20.0) | |
| 2 | 433 (22.1) | 219 (18.1) | 139 (22.7) | 171 (21.3) | Sema/lira/placebo: 25 (19.8)/29 (22.8)/21 (24.7) | |
| 3 | 279 (14.2) | 317 (26.2) | 100 (16.4) | 111 (13.8) | Sema/lira/placebo: 17 (13.5)/24 (18.9)/9 (10.6) | |
| 4 | 139 (7.1) | 290 (24.0) | 45 (7.4) | 53 (6.6) | Sema/lira/placebo: 10 (7.9)/11 (8.7)/9 (10.6) | |
| ≥5 | 95 (4.8) | 260 (21.5) | 33 (5.4) | 16 (2.0) | Sema/lira/placebo: 11 (8.7)/9 (7.1)/13 (15.3) |
Abbreviations: BMI, body mass index; HbA1c, glycated haemoglobin; IWQOL‐Lite‐CT, impact of weight on quality of life‐lite clinical trials version questionnaire; lira, liraglutide; NA, not available; SD, standard deviation; sema, semaglutide; SF‐36, short form‐36 version 2 health survey, acute version.
Key inclusion criteria for STEP 1, 3‐5 and 8 trials were age ≥18 years, BMI ≥30 kg/m2 or ≥27 kg/m2 with ≥1 weight‐related comorbidity (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease, history of at least one self‐reported unsuccessful dietary effort to lose weight and no type 1 or type 2 diabetes.
Key inclusion criteria for the STEP 2 trial were age ≥18 years, type 2 diabetes diagnosed ≥180 days prior, BMI ≥27 kg/m2, HbA1c 7%‐10% (53‐86 mmol/mol) and treatment with diet and exercise alone or stable treatment with metformin, sulphonylurea, sodium‐glucose co‐transporter‐2 inhibitor, glitazone as single‐agent therapy or ≤3 agents for diabetes according to local label.
Native American, Alaska Native, Native Hawaiian, other Pacific Islander and other ethnic group. In STEP 1, this category included participants who answered ‘not applicable’, which is the way race or ethnic group was recorded in France.
For STEP 1, the presence of prediabetes was determined by investigators based on available information (e.g. medical records, concomitant medication and blood glucose variables) and in accordance with American Diabetes Association criteria.
Information collected at screening on comorbidities was based on medical history and included: type 2 diabetes (STEP 2 only), dyslipidaemia, hypertension, coronary artery disease, cerebrovascular disease, obstructive sleep apnoea, impaired glucose metabolism (not included for STEP 2), reproductive system disorders, liver disease, kidney disease, osteoarthritis, gout, thyroid disease (STEP 3 only) and asthma or chronic obstructive pulmonary disease.