Table 1.
Summary of end-of-treatment changes in key outcomes in seven STEP trials (semaglutide) and three SURMOUNT trials (tirzepatide)
| Trial name | Treatment arms (N); trial duration, weeks | Baseline weight, % Δ | SBP, mm Hg | DBP, mm Hg | HbA1c, percentage points | Triglyceridesa | Total cholesterola | HDLa | LDLa | C-reactive proteina | Waist circumference, cm | SF-36, physical function score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| STEP 1 | Semaglutide 2.4 mg + lifestyle intervention (1306); 68 wk | − 14.9* | − 6.2* | − 2.8* | − 0.5* | 0.78* | 0.97* | 1.05* | 0.97* | 0.47* | − 13.5* | 2.2* |
| Placebo + lifestyle intervention (655) | − 2.4 | − 1.1 | − 0.4 | − 0.2 | 0.93 | 1.00 | 1.01 | 1.01 | 0.85 | − 4.1 | 0.4 | |
| STEP 2 | Semaglutide 2.4 mg + lifestyle intervention (404); 68 wk | − 9.6* | − 3.9* | − 1.6 | − 1.6* | 0.78 | 0.99 | 1.07 | 1.00 | 0.51 | − 9.4* | 2.5* |
| Semaglutide 1.0 mg + lifestyle intervention (403)^ | − 7.0 | − 2.9 | − 0.6 | − 1.5 | 0.83 | 0.98 | 1.05 | 0.99 | 0.58 | − 6.7 | 2.4 | |
| Placebo + lifestyle intervention (403) | − 3.4 | − 0.5 | − 0.9 | − 0.4 | 0.91 | 0.99 | 1.04 | 1.00 | 0.83 | − 4.5 | 1.0 | |
| STEP 3 | Semaglutide 2.4 mg + low calorie diet for the first 8 weeks + intensive behavioral therapy (407); 68 wk | − 16.0* | − 5.6* | − 3.0* | − 0.5* | − 22.50%* | − 3.80%* | 6.50% | − 4.70%* | 59.60%* | − 14.6* | 2.4 |
| Placebo + low calorie diet for the first 8 weeks + intensive behavioral therapy (204) | − 5.7 | − 1.6 | − 0.8 | − 0.3 | − 6.50% | 2.10% | 5.00% | 2.60% | − 22.90% | − 6.3 | 1.6 | |
| STEP 4b | Continued semaglutide 2.4 mg + lifestyle intervention (535); 68 wk | − 7.9* | 0.5* | 0.3 | − 0.1* | − 6.00%* | 5.00%* | 18.00% | 1.00%* | NR | − 6.4* | 1.0* |
| Switched to placebo + lifestyle intervention (268) | 6.9 | 4.4 | 0.9 | 0.1 | 15.00% | 11.00% | 18.00% | 8.00% | NR | 3.3 | − 1.5 | |
| STEP 5 | Semaglutide 2.4 mg + lifestyle intervention (152); 104 wk | − 15.2* | − 5.7* | − 4.4 | − 0.4 | − 19.00% | − 3.30% | 9.60% | − 6.10% | − 56.70% | − 14.4* | NR |
| Placebo + lifestyle intervention (152) | − 2.6 | − 1.6 | − 0.8 | − 0.1 | 3.70% | 1.40% | 8.10% | − 2.70% | − 7.80% | − 5.2 | NR | |
| STEP 6 | Semaglutide 2.4 mg + lifestyle intervention (199); 68 wk | − 13.2* | − 10.8 | − 5.3 | − 0.9 | 0.79 | 0.91 | 1.09 | 0.85 | 0.42 | − 11.1* | 0.8 |
| Semaglutide 1.7 mg + lifestyle intervention (101) | − 9.6* | − 10.8 | − 4.6 | − 0.9 | 0.80 | 0.93 | 1.07 | 0.90 | 0.62 | − 7.7* | − 0.1 | |
| Placebo + lifestyle intervention (101) | − 2.1 | − 5.3 | − 2.2 | − 0.0 | 1.06 | 1.01 | 1.06 | 0.96 | 0.89 | − 1.8 | − 0.3 | |
| STEP 8 | Semaglutide 2.4 mg + lifestyle intervention (126); 68 wk | − 15.8* | − 5.7 | − 5.0 | − 0.2 | − 20.70% | − 7.10% | − 0.30% | − 6.50% | − 52.60% | − 13.2 | NR |
| Liraglutide 3.0 mg + lifestyle intervention (127) | − 6.4* | − 2.9 | − 0.5 | − 0.1 | − 11.00% | − 0.10% | 1.90% | 0.90% | − 24.50% | − 6.6 | NR | |
| Placebo + lifestyle intervention (85) | − 1.9 | 3.2 | 0.7 | 0.1 | − 3.20% | − 3.30% | − 0.90% | − 1.10% | − 20.10% | − 2.0 | NR | |
| SURMOUNT 1c | Tirzepatide 5.0 mg + lifestyle intervention (630); 72 wk | − 15.0* | − 7.0 | − 5.2 | − 0.4 | − 24.30% | − 4.90% | 7.00% | − 5.30% | NR | − 14.0* | 3.9 |
| Tirzepatide 10.0 mg + lifestyle intervention (636) | − 19.5* | − 8.2 | − 5.5 | − 0.5 | − 27.00% | − 5.60% | 8.60% | − 6.60% | NR | − 17.7* | 3.9 | |
| Tirzepatide 15.0 mg + lifestyle intervention (630) | − 20.9* | − 7.6 | − 4.6 | − 0.5 | − 31.40% | − 7.40% | 8.20% | − 8.60% | NR | − 18.5* | 4.2 | |
| Placebo + lifestyle intervention (643) | − 3.1 | − 1.2 | − 1.0 | − 0.1 | − 6.30% | − 1.10% | 0.20% | − 0.90% | NR | − 4.0 | 1.9 | |
| SURMOUNT 2d | Tirzepatide 10.0 mg + lifestyle intervention (312); 72 wk | − 12.8* | − 5.9 | − 2.1 | − 2.1* | − 26.80%* | − 3.00%* | 6.90%* | 2.30% | NR | − 10.8* | 3.4* |
| Tirzepatide 15.0 mg + lifestyle intervention (311) | − 14.7* | − 7.7 | − 2.9 | − 2.1* | − 30.60%* | − 2.20%* | 9.60%* | 3.20% | NR | − 13.1* | 3.8* | |
| Placebo + lifestyle intervention (315) | − 3.2 | − 1.2 | − 0.3 | − 0.5 | − 5.80% | 2.10% | 1.10% | 6.30% | NR | − 3.3 | 1.6 | |
| SURMOUNT 3c,e | Tirzepatide MTD + quarterly lifestyle intervention (287); 72 wk | − 18.4* | − 5.1 | − 3.2 | − 0.5 | − 25.80% | − 3.00% | 15.40% | − 6.10% | NR | − 14.6* | 3.3 |
| Placebo + quarterly lifestyle intervention (292) | 2.5 | 4.1 | 2.3 | 0.0 | 3.00% | 5.20% | 3.60% | 6.10% | NR | 0.2 | − 0.6 |
This table is adapted and updated from Table 1 in reference [57], originally published in Trends in Cardiovascular Medicine, vol 33: Chao, AM, Tronieri JS, Amaro A, Wadden TA; Semaglutide for the treatment of obesity, pp 159–166, Copyright Elsevier 2023
SBP systolic blood pressure, DBP diastolic blood pressure, NR not reported, MTD max tolerated dose
*p < 0.05 with comparison to placebo. ^Formal statistical comparisons were not performed between semaglutide 1.0 mg and placebo
aFor STEP trials 1, 2, and 6, lipid values presented are a ratio of week 68 to baseline. For STEP trials 3, 4, 5, 8, and SURMOUNT trials 1, 2, and 3, values presented are percent change
bAll participants were treated with semaglutide from baseline to 20 weeks. Results presented are changes from weeks 20–68
cEfficacy estimand used for SBP, DBP, HbA1c, triglycerides, total cholesterol, HDL, LDL, and SF-36 physical functioning score. Formal statistical comparisons were not performed
dEfficacy estimand used for SBP, DBP, triglycerides, total cholesterol, HDL, LDL, and SF-36 physical functioning score
ePrior to randomization, all participants were required to complete a 12-week lead-in program that provided intensive lifestyle intervention alone. Those who successfully lost ≥ 5% of their baseline weight (and met other eligibility criteria) were randomly assigned to tirzepatide or placebo. Results shown in the table are from randomization to week 72 and do not reflect changes in weight (− 6.9% reduction in lead-in weight during the 12 weeks) and other outcomes that occurred during the lead-in program