Key clinical trials conducted with each weight loss intervention, along with their findings
| Trial . | Population . | Sample size . | Baseline weight (kg) . | Follow-up (weeks) . | Weight loss (%) . | Change in pulse (b.p.m.) . | Change in SBP (mmHg) . | Change in DBP (mmHg) . | Change in LDL . | Change in HDL . | Change in TGs . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Intensive lifestyle intervention | |||||||||||
| Look AHEAD, 201319 | BMI ≥25 kg/m2 Diabetes | ILI: 2570 DSE: 2575 | ILI: 101 DSE: 101 | 499 | ILI: −6.0a DSE: −3.5 | N/A | ILI: −2b DSE: −2 | ILI: −3.7 DSE: −4.5 | ILI: −22.5 mg/dLb DSE: −23.7 mg/dL | ILI: +5.2 mg/dLb DSE: +4.3 mg/dL | ILI: −31 mg/dL DSE: −30 mg/dL |
| Diabetes Prevention Programme, 200220 | BMI ≥24 kg/m2 Pre-diabetes | ILI: 1079 Met: 1073 Pla: 1082 | ILI: 94 Met: 94 Pla: 94 | 146 | ILI: −6.0a Met: −2.1a Pla: −0.1 | N/A | N/A | N/A | N/A | N/A | N/A |
| Liraglutide | |||||||||||
| SCALE Obesity and Prediabetes, 201521 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if untreated weight-related comorbidities present) No Type 2 diabetes | Lira 3.0 mg SQ OD: 2487 Pla: 1244 | Lira 3.0: 106 Pla: 106 | 56 | Lira 3.0: −8.0a Pla: −2.6 | Lira 3.0: +2.5a Pla: 0.1 | Lira 3.0: −4.2a Pla: −1.5 | Lira 3.0: −2.6a Pla: −1.9 | Lira 3.0: −3.0%a Pla: −1.0% | Lira 3.0: +2.3%a Pla: +0.7% | Lira 3.0: −13.3%a Pla: −5.5% |
| SCALE Diabetes, 201522 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | Lira 3.0 mg SQ OD: 423 Lira 1.8 mg SQ OD: 211 Pla: 212 | Lira 3.0: 106 Lira 1.8: 106 Pla: 107 | 56 | Lira 3.0: −6.0a Lira 1.8: −4.7a Pla: −2.0 | N/A | Lira 3.0: −2.8a Lira 1.8: −3.5a Pla: −0.4 | Lira 3.0: −0.9 Lira 1.8: −1.1 Pla: −0.5 | Lira 3.0: −0.6% Lira 1.8: −3.1% Pla: +5.0% | Lira 3.0: +4.7%a Lira 1.8: +4.5% Pla: + 1.9% | Lira 3.0: −14.7%a Lira 1.8: −9.5% Pla: +0.4% |
| Semaglutide | |||||||||||
| STEP 1 trial, 202123 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if untreated weight-related comorbidities present) No Type 2 diabetes | Sema 2.4 mg SQ OW: 1306 Pla: 655 | Sema 2.4: 105 Pla: 105 | 68 | Sema 2.4: −14.9a Pla: −2.4 | Sema 2.4: −3.5a Pla: −0.7 | Sema 2.4: −6.2a Pla: −1.1 | Sema 2.4: −2.8a Pla: −0.4 | Sema 2.4: −3.0%a Pla: +1% | Sema 2.4: +5.0%a Pla: +1% | Sema 2.4: −22.0%a Pla: −7% |
| STEP 2 trial, 202124 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | Sema 2.4 mg SQ OW: 404 Sema 1.0 mg SQ OW: 403 Pla: 403 | Sema 2.4: 100 Sema 1.0: 99 Pla: 101 | 68 | Sema 2.4: −9.64a Sema 1.0: −7.0a Pla: −3.42 | N/A | Sema 2.4: −3.9a Sema 1.0: −2.9a Pla: −0.5 | Sema 2.4: −1.6 Sema 1.0: −0.6 Pla: −0.9 | Sema 2.4: 0% Sema 1.0: −1.0% Pla: 0% | Sema 2.4: +7% Sema 1.0: +5% Pla: +4% | Sema 2.4: −22%a Sema 1.0: −17%a Pla: −9% |
| STEP 3 trial, 202125 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | Sema 2.4 mg SQ OW: 407 Pla: 204 | Sema 2.4: 107 Pla: 104 | 68 | Sema 2.4: −16.0a Pla: −5.7 | N/A | Sema 2.4: −5.6a Pla: −1.6 | Sema 2.4: −3.0a Pla: −0.8 | Sema 2.4: −4.7%a Pla: +2.6% | Sema 2.4: +6.5% Pla: +5.0% | Sema 2.4: −22.5%a Pla: −6.5% |
| Tirzepatide | |||||||||||
| SURMOUNT-1, 202226 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | Tirze 5 mg SQ OW: 630 Tirze 10 mg SQ OW: 636 Tirze 15 mg SQ OW: 630 Pla: 643 | Tirze 5: 103 Tirze 10: 106 Tirze 15: 106 Pla: 105 | 72 | Tirze 5: −15.0a Tirze 10: −19.5a Tirze 15: −20.9a Pla: −3.1 | Tirze: +1.8a Pla: +0.1 | Tirze: −7.2a Pla: −1.0 | Tirze: −4.8a Pla: −0.8 | Tirze: −5.8%a Pla: −1.7% | Tirze: +8.0%a Pla: −0.7% | Tirze: −24.8%a Pla: −5.6% |
| Naltrexone/bupropion | |||||||||||
| COR-I, 201027 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 583 NB 16/360 mg per day (in 2 doses): 578 Placebo: 581 | NB 32: 100 NB 16: 100 Pla: 100 | 56 | NB 32: −6.1a NB 16: −Pla: −1.3 | NB 32: +0.4a NB 16: +1.1a Pla: −1.0 | NB 32: −0.1a NB 16: +0.3a Pla: −1.9 | NB 32: 0.0a NB 16: +0.1a Pla: −0.9 | NB 32: −2.0%a NB 16: −1.5%a Pla: −0.5% | NB 32: +8.0%a NB 16: +7.6%a Pla: +0.8% | NB 32: −12.7%a NB 16: −8.0%a Pla: −3.1% |
| COR-II, 201328 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 1001 Placebo: 495 | NB 32: 100 Pla: 99 | 56 | NB 32: −6.4a Pla: −1.2 | NB 32: +0.8a Pla: −0.3 | NB 32: +0.6a Pla: −0.5 | NB 32: +0.4 Pla: +0.3 | NB 32: −6.2 mg/dLa Pla: −2.1 mg/dL | NB 32: +3.6 mg/dLa Pla: −0.9 mg/dL | NB 32: −9.8%a Pla: −0.5% |
| COR-BMOD, 201129 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 591 Placebo: 202 | NB 32: 102 Pla: 100 | 56 | NB 32: −9.3a Pla: −5.1 | NB 32: +1.1 Pla: +0.2 | NB 32: −1.3 Pla: −3.9 | NB 32: −1.4 Pla: −2.8 | NB 32: +7.1% Pla: +10.0% | NB 32: +9.4%a Pla: +2.8% | NB 32: −16.6%a Pla: −8.5% |
| COR-Diabetes, 201330 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | NB 32/360 mg per day (in 2 doses): 265 Placebo: 159 | NB 32: 106 Pla: 105 | 56 | NB 32: −5.0a Pla: −1.8 | N/A | NB 32: 0 Pla: −1.1 | NB 32: −1.1 Pla: −1.5 | NB 32: −1.4 mg/dL Pla: 0 mg/dL | NB 32: +3.0a mg/dL Pla: −0.3 mg/dL | NB 32: −11.2%a Pla: −0.8% |
| LIGHT, 201631 | BMI ≥27 kg/m2 Diabetes (with hypertension, dyslipidaemia, low HDL, or smoker) | NB 32/360 mg per day (in 2 doses): 4455 Placebo: 4450 | NB 32 mg: 105 Pla: 106 | 208 | NB 32 mg: −3.71a Pla:−1.13 | NB 32: +0.7 Pla: +0.6 | NB 32: +1.4 Pla: +0.5 | N/A | N/A | N/A | N/A |
| Orlistat | |||||||||||
| Chanoine et al, 200532 | Adolescents BMI ≥2 units of 95th percentile (12 years: >28.5 boys, >29.5 girls; 16 years: 31.8 boys, 31.9 girls) Exclude Type 2 diabetes requiring medication | Orl 120 mg (3× day): 352 Placebo: 181 | Orl 120: 98 Pla: 95 | 54 | Orl 120: +0.54a Pla: +3.3 | N/A | Orl 120: +1.09 Pla: +1.31 | Orl 120: −0.51a Pla: +1.30 | Orl 120: −0.99 Pla: +0.88 | Orl 120: +0.07 Pla: −0.31 | Orl 120: +17.9 Pla: +11.68 |
| Sjöström et al., 199833 | BMI ≥28 kg/m2 Exclude Type 2 diabetes requiring medication | Orl 120 mg (3× day): 343 Placebo: 340 | Orl 120: 99 Pla: 100 | 52 | Orl 120: −10.2a Pla: −6.1 | N/A | Orl 120: −6a Pla: −3 | Orl 120: −4.5a Pla: −2.7 | Orl 120: −0.36 mmol/La Pla: −0.04 mmol/L | Orl 120: + 0.07 mmol/L Pla: −0.32 mmol/L | Orl 120: −0.13 mmol/L Pla: −0.13 mmol/L |
| Bariatric surgery | |||||||||||
| STAMPEDE, 201734 | BMI ≥27 kg/m2 HbA1c > 7.0% | GB: 49 SG: 47 MT: 38 | GB: 107 SG: 100 MT: 105 | 260 | GB: −21.7a SG: −18.5a MT: −5.0 | NA | GB: −3.3c SG: −8.4c MT: −4.1 | GB: −5.8c SG: −8.1c MT: −4.4 | GB: +12.4%c SG: +16.6%c MT: +3.7% | GB: +31.9%a SG: +29.6%a MT: +7.0% | GB: −39.8%a SG: −29.4%a MT: −8.3% |
| GATEWAY, 201835 | BMI ≥30 kg/m2 Hypertension No diabetes | GB: 50 MT: 50 | GB: 102 MT: 100 | 52 | GB: −28.9a MT: −0.69 | N/A | GB: +0.8c MT: +5.2 | GB: −0.4c MT: +2.4 | GB: −35.0a MT: −7.4 | GB: +9.8a MT: +1.7 | GB: −81.5a MT: −22.9 |
| Trial . | Population . | Sample size . | Baseline weight (kg) . | Follow-up (weeks) . | Weight loss (%) . | Change in pulse (b.p.m.) . | Change in SBP (mmHg) . | Change in DBP (mmHg) . | Change in LDL . | Change in HDL . | Change in TGs . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Intensive lifestyle intervention | |||||||||||
| Look AHEAD, 201319 | BMI ≥25 kg/m2 Diabetes | ILI: 2570 DSE: 2575 | ILI: 101 DSE: 101 | 499 | ILI: −6.0a DSE: −3.5 | N/A | ILI: −2b DSE: −2 | ILI: −3.7 DSE: −4.5 | ILI: −22.5 mg/dLb DSE: −23.7 mg/dL | ILI: +5.2 mg/dLb DSE: +4.3 mg/dL | ILI: −31 mg/dL DSE: −30 mg/dL |
| Diabetes Prevention Programme, 200220 | BMI ≥24 kg/m2 Pre-diabetes | ILI: 1079 Met: 1073 Pla: 1082 | ILI: 94 Met: 94 Pla: 94 | 146 | ILI: −6.0a Met: −2.1a Pla: −0.1 | N/A | N/A | N/A | N/A | N/A | N/A |
| Liraglutide | |||||||||||
| SCALE Obesity and Prediabetes, 201521 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if untreated weight-related comorbidities present) No Type 2 diabetes | Lira 3.0 mg SQ OD: 2487 Pla: 1244 | Lira 3.0: 106 Pla: 106 | 56 | Lira 3.0: −8.0a Pla: −2.6 | Lira 3.0: +2.5a Pla: 0.1 | Lira 3.0: −4.2a Pla: −1.5 | Lira 3.0: −2.6a Pla: −1.9 | Lira 3.0: −3.0%a Pla: −1.0% | Lira 3.0: +2.3%a Pla: +0.7% | Lira 3.0: −13.3%a Pla: −5.5% |
| SCALE Diabetes, 201522 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | Lira 3.0 mg SQ OD: 423 Lira 1.8 mg SQ OD: 211 Pla: 212 | Lira 3.0: 106 Lira 1.8: 106 Pla: 107 | 56 | Lira 3.0: −6.0a Lira 1.8: −4.7a Pla: −2.0 | N/A | Lira 3.0: −2.8a Lira 1.8: −3.5a Pla: −0.4 | Lira 3.0: −0.9 Lira 1.8: −1.1 Pla: −0.5 | Lira 3.0: −0.6% Lira 1.8: −3.1% Pla: +5.0% | Lira 3.0: +4.7%a Lira 1.8: +4.5% Pla: + 1.9% | Lira 3.0: −14.7%a Lira 1.8: −9.5% Pla: +0.4% |
| Semaglutide | |||||||||||
| STEP 1 trial, 202123 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if untreated weight-related comorbidities present) No Type 2 diabetes | Sema 2.4 mg SQ OW: 1306 Pla: 655 | Sema 2.4: 105 Pla: 105 | 68 | Sema 2.4: −14.9a Pla: −2.4 | Sema 2.4: −3.5a Pla: −0.7 | Sema 2.4: −6.2a Pla: −1.1 | Sema 2.4: −2.8a Pla: −0.4 | Sema 2.4: −3.0%a Pla: +1% | Sema 2.4: +5.0%a Pla: +1% | Sema 2.4: −22.0%a Pla: −7% |
| STEP 2 trial, 202124 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | Sema 2.4 mg SQ OW: 404 Sema 1.0 mg SQ OW: 403 Pla: 403 | Sema 2.4: 100 Sema 1.0: 99 Pla: 101 | 68 | Sema 2.4: −9.64a Sema 1.0: −7.0a Pla: −3.42 | N/A | Sema 2.4: −3.9a Sema 1.0: −2.9a Pla: −0.5 | Sema 2.4: −1.6 Sema 1.0: −0.6 Pla: −0.9 | Sema 2.4: 0% Sema 1.0: −1.0% Pla: 0% | Sema 2.4: +7% Sema 1.0: +5% Pla: +4% | Sema 2.4: −22%a Sema 1.0: −17%a Pla: −9% |
| STEP 3 trial, 202125 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | Sema 2.4 mg SQ OW: 407 Pla: 204 | Sema 2.4: 107 Pla: 104 | 68 | Sema 2.4: −16.0a Pla: −5.7 | N/A | Sema 2.4: −5.6a Pla: −1.6 | Sema 2.4: −3.0a Pla: −0.8 | Sema 2.4: −4.7%a Pla: +2.6% | Sema 2.4: +6.5% Pla: +5.0% | Sema 2.4: −22.5%a Pla: −6.5% |
| Tirzepatide | |||||||||||
| SURMOUNT-1, 202226 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | Tirze 5 mg SQ OW: 630 Tirze 10 mg SQ OW: 636 Tirze 15 mg SQ OW: 630 Pla: 643 | Tirze 5: 103 Tirze 10: 106 Tirze 15: 106 Pla: 105 | 72 | Tirze 5: −15.0a Tirze 10: −19.5a Tirze 15: −20.9a Pla: −3.1 | Tirze: +1.8a Pla: +0.1 | Tirze: −7.2a Pla: −1.0 | Tirze: −4.8a Pla: −0.8 | Tirze: −5.8%a Pla: −1.7% | Tirze: +8.0%a Pla: −0.7% | Tirze: −24.8%a Pla: −5.6% |
| Naltrexone/bupropion | |||||||||||
| COR-I, 201027 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 583 NB 16/360 mg per day (in 2 doses): 578 Placebo: 581 | NB 32: 100 NB 16: 100 Pla: 100 | 56 | NB 32: −6.1a NB 16: −Pla: −1.3 | NB 32: +0.4a NB 16: +1.1a Pla: −1.0 | NB 32: −0.1a NB 16: +0.3a Pla: −1.9 | NB 32: 0.0a NB 16: +0.1a Pla: −0.9 | NB 32: −2.0%a NB 16: −1.5%a Pla: −0.5% | NB 32: +8.0%a NB 16: +7.6%a Pla: +0.8% | NB 32: −12.7%a NB 16: −8.0%a Pla: −3.1% |
| COR-II, 201328 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 1001 Placebo: 495 | NB 32: 100 Pla: 99 | 56 | NB 32: −6.4a Pla: −1.2 | NB 32: +0.8a Pla: −0.3 | NB 32: +0.6a Pla: −0.5 | NB 32: +0.4 Pla: +0.3 | NB 32: −6.2 mg/dLa Pla: −2.1 mg/dL | NB 32: +3.6 mg/dLa Pla: −0.9 mg/dL | NB 32: −9.8%a Pla: −0.5% |
| COR-BMOD, 201129 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 591 Placebo: 202 | NB 32: 102 Pla: 100 | 56 | NB 32: −9.3a Pla: −5.1 | NB 32: +1.1 Pla: +0.2 | NB 32: −1.3 Pla: −3.9 | NB 32: −1.4 Pla: −2.8 | NB 32: +7.1% Pla: +10.0% | NB 32: +9.4%a Pla: +2.8% | NB 32: −16.6%a Pla: −8.5% |
| COR-Diabetes, 201330 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | NB 32/360 mg per day (in 2 doses): 265 Placebo: 159 | NB 32: 106 Pla: 105 | 56 | NB 32: −5.0a Pla: −1.8 | N/A | NB 32: 0 Pla: −1.1 | NB 32: −1.1 Pla: −1.5 | NB 32: −1.4 mg/dL Pla: 0 mg/dL | NB 32: +3.0a mg/dL Pla: −0.3 mg/dL | NB 32: −11.2%a Pla: −0.8% |
| LIGHT, 201631 | BMI ≥27 kg/m2 Diabetes (with hypertension, dyslipidaemia, low HDL, or smoker) | NB 32/360 mg per day (in 2 doses): 4455 Placebo: 4450 | NB 32 mg: 105 Pla: 106 | 208 | NB 32 mg: −3.71a Pla:−1.13 | NB 32: +0.7 Pla: +0.6 | NB 32: +1.4 Pla: +0.5 | N/A | N/A | N/A | N/A |
| Orlistat | |||||||||||
| Chanoine et al, 200532 | Adolescents BMI ≥2 units of 95th percentile (12 years: >28.5 boys, >29.5 girls; 16 years: 31.8 boys, 31.9 girls) Exclude Type 2 diabetes requiring medication | Orl 120 mg (3× day): 352 Placebo: 181 | Orl 120: 98 Pla: 95 | 54 | Orl 120: +0.54a Pla: +3.3 | N/A | Orl 120: +1.09 Pla: +1.31 | Orl 120: −0.51a Pla: +1.30 | Orl 120: −0.99 Pla: +0.88 | Orl 120: +0.07 Pla: −0.31 | Orl 120: +17.9 Pla: +11.68 |
| Sjöström et al., 199833 | BMI ≥28 kg/m2 Exclude Type 2 diabetes requiring medication | Orl 120 mg (3× day): 343 Placebo: 340 | Orl 120: 99 Pla: 100 | 52 | Orl 120: −10.2a Pla: −6.1 | N/A | Orl 120: −6a Pla: −3 | Orl 120: −4.5a Pla: −2.7 | Orl 120: −0.36 mmol/La Pla: −0.04 mmol/L | Orl 120: + 0.07 mmol/L Pla: −0.32 mmol/L | Orl 120: −0.13 mmol/L Pla: −0.13 mmol/L |
| Bariatric surgery | |||||||||||
| STAMPEDE, 201734 | BMI ≥27 kg/m2 HbA1c > 7.0% | GB: 49 SG: 47 MT: 38 | GB: 107 SG: 100 MT: 105 | 260 | GB: −21.7a SG: −18.5a MT: −5.0 | NA | GB: −3.3c SG: −8.4c MT: −4.1 | GB: −5.8c SG: −8.1c MT: −4.4 | GB: +12.4%c SG: +16.6%c MT: +3.7% | GB: +31.9%a SG: +29.6%a MT: +7.0% | GB: −39.8%a SG: −29.4%a MT: −8.3% |
| GATEWAY, 201835 | BMI ≥30 kg/m2 Hypertension No diabetes | GB: 50 MT: 50 | GB: 102 MT: 100 | 52 | GB: −28.9a MT: −0.69 | N/A | GB: +0.8c MT: +5.2 | GB: −0.4c MT: +2.4 | GB: −35.0a MT: −7.4 | GB: +9.8a MT: +1.7 | GB: −81.5a MT: −22.9 |
SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; BMI, body mass index; Look AHEAD, Action for Health in Diabetes; ILI, intensive lifestyle intervention; DSE, diabetes support and education; Met, metformin; Pla, placebo; N/A, not available; SCALE, Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities; Lira, liraglutide; STEP, Semaglutide Treatment Effect in People with Obesity; Sema, semaglutide; SURMOUNT, A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight; Tirze, Tirzepatide; DP, diethylpropion; NB, naltrexone/bupropion; COR, A Study of the Safety and Efficacy of Two Doses of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects; NB, Naltrexone/bupropion; LIGHT, Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors; Orl, orlistat; STAMPEDE, Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently; GB, Gastric bypass; SG, sleeve gastrectomy; MT, medical therapy; GATEWAY, Gastric Bypass to Treat Obese Patients With Steady Hypertension.
aP < .05 for intervention vs. control.
bAlthough values for these parameters were similar between the ILI and DSE groups at the end of the trial, a significant improvement was noted with ILI on average over the entire trial period.
cA significant benefit of the intervention on this parameter was not observed likely due to lower anti-hypertensive/anti-lipidaemic drug use in the intervention arm/anti-lipidaemic drug use in the intervention arm.
Key clinical trials conducted with each weight loss intervention, along with their findings
| Trial . | Population . | Sample size . | Baseline weight (kg) . | Follow-up (weeks) . | Weight loss (%) . | Change in pulse (b.p.m.) . | Change in SBP (mmHg) . | Change in DBP (mmHg) . | Change in LDL . | Change in HDL . | Change in TGs . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Intensive lifestyle intervention | |||||||||||
| Look AHEAD, 201319 | BMI ≥25 kg/m2 Diabetes | ILI: 2570 DSE: 2575 | ILI: 101 DSE: 101 | 499 | ILI: −6.0a DSE: −3.5 | N/A | ILI: −2b DSE: −2 | ILI: −3.7 DSE: −4.5 | ILI: −22.5 mg/dLb DSE: −23.7 mg/dL | ILI: +5.2 mg/dLb DSE: +4.3 mg/dL | ILI: −31 mg/dL DSE: −30 mg/dL |
| Diabetes Prevention Programme, 200220 | BMI ≥24 kg/m2 Pre-diabetes | ILI: 1079 Met: 1073 Pla: 1082 | ILI: 94 Met: 94 Pla: 94 | 146 | ILI: −6.0a Met: −2.1a Pla: −0.1 | N/A | N/A | N/A | N/A | N/A | N/A |
| Liraglutide | |||||||||||
| SCALE Obesity and Prediabetes, 201521 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if untreated weight-related comorbidities present) No Type 2 diabetes | Lira 3.0 mg SQ OD: 2487 Pla: 1244 | Lira 3.0: 106 Pla: 106 | 56 | Lira 3.0: −8.0a Pla: −2.6 | Lira 3.0: +2.5a Pla: 0.1 | Lira 3.0: −4.2a Pla: −1.5 | Lira 3.0: −2.6a Pla: −1.9 | Lira 3.0: −3.0%a Pla: −1.0% | Lira 3.0: +2.3%a Pla: +0.7% | Lira 3.0: −13.3%a Pla: −5.5% |
| SCALE Diabetes, 201522 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | Lira 3.0 mg SQ OD: 423 Lira 1.8 mg SQ OD: 211 Pla: 212 | Lira 3.0: 106 Lira 1.8: 106 Pla: 107 | 56 | Lira 3.0: −6.0a Lira 1.8: −4.7a Pla: −2.0 | N/A | Lira 3.0: −2.8a Lira 1.8: −3.5a Pla: −0.4 | Lira 3.0: −0.9 Lira 1.8: −1.1 Pla: −0.5 | Lira 3.0: −0.6% Lira 1.8: −3.1% Pla: +5.0% | Lira 3.0: +4.7%a Lira 1.8: +4.5% Pla: + 1.9% | Lira 3.0: −14.7%a Lira 1.8: −9.5% Pla: +0.4% |
| Semaglutide | |||||||||||
| STEP 1 trial, 202123 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if untreated weight-related comorbidities present) No Type 2 diabetes | Sema 2.4 mg SQ OW: 1306 Pla: 655 | Sema 2.4: 105 Pla: 105 | 68 | Sema 2.4: −14.9a Pla: −2.4 | Sema 2.4: −3.5a Pla: −0.7 | Sema 2.4: −6.2a Pla: −1.1 | Sema 2.4: −2.8a Pla: −0.4 | Sema 2.4: −3.0%a Pla: +1% | Sema 2.4: +5.0%a Pla: +1% | Sema 2.4: −22.0%a Pla: −7% |
| STEP 2 trial, 202124 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | Sema 2.4 mg SQ OW: 404 Sema 1.0 mg SQ OW: 403 Pla: 403 | Sema 2.4: 100 Sema 1.0: 99 Pla: 101 | 68 | Sema 2.4: −9.64a Sema 1.0: −7.0a Pla: −3.42 | N/A | Sema 2.4: −3.9a Sema 1.0: −2.9a Pla: −0.5 | Sema 2.4: −1.6 Sema 1.0: −0.6 Pla: −0.9 | Sema 2.4: 0% Sema 1.0: −1.0% Pla: 0% | Sema 2.4: +7% Sema 1.0: +5% Pla: +4% | Sema 2.4: −22%a Sema 1.0: −17%a Pla: −9% |
| STEP 3 trial, 202125 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | Sema 2.4 mg SQ OW: 407 Pla: 204 | Sema 2.4: 107 Pla: 104 | 68 | Sema 2.4: −16.0a Pla: −5.7 | N/A | Sema 2.4: −5.6a Pla: −1.6 | Sema 2.4: −3.0a Pla: −0.8 | Sema 2.4: −4.7%a Pla: +2.6% | Sema 2.4: +6.5% Pla: +5.0% | Sema 2.4: −22.5%a Pla: −6.5% |
| Tirzepatide | |||||||||||
| SURMOUNT-1, 202226 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | Tirze 5 mg SQ OW: 630 Tirze 10 mg SQ OW: 636 Tirze 15 mg SQ OW: 630 Pla: 643 | Tirze 5: 103 Tirze 10: 106 Tirze 15: 106 Pla: 105 | 72 | Tirze 5: −15.0a Tirze 10: −19.5a Tirze 15: −20.9a Pla: −3.1 | Tirze: +1.8a Pla: +0.1 | Tirze: −7.2a Pla: −1.0 | Tirze: −4.8a Pla: −0.8 | Tirze: −5.8%a Pla: −1.7% | Tirze: +8.0%a Pla: −0.7% | Tirze: −24.8%a Pla: −5.6% |
| Naltrexone/bupropion | |||||||||||
| COR-I, 201027 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 583 NB 16/360 mg per day (in 2 doses): 578 Placebo: 581 | NB 32: 100 NB 16: 100 Pla: 100 | 56 | NB 32: −6.1a NB 16: −Pla: −1.3 | NB 32: +0.4a NB 16: +1.1a Pla: −1.0 | NB 32: −0.1a NB 16: +0.3a Pla: −1.9 | NB 32: 0.0a NB 16: +0.1a Pla: −0.9 | NB 32: −2.0%a NB 16: −1.5%a Pla: −0.5% | NB 32: +8.0%a NB 16: +7.6%a Pla: +0.8% | NB 32: −12.7%a NB 16: −8.0%a Pla: −3.1% |
| COR-II, 201328 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 1001 Placebo: 495 | NB 32: 100 Pla: 99 | 56 | NB 32: −6.4a Pla: −1.2 | NB 32: +0.8a Pla: −0.3 | NB 32: +0.6a Pla: −0.5 | NB 32: +0.4 Pla: +0.3 | NB 32: −6.2 mg/dLa Pla: −2.1 mg/dL | NB 32: +3.6 mg/dLa Pla: −0.9 mg/dL | NB 32: −9.8%a Pla: −0.5% |
| COR-BMOD, 201129 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 591 Placebo: 202 | NB 32: 102 Pla: 100 | 56 | NB 32: −9.3a Pla: −5.1 | NB 32: +1.1 Pla: +0.2 | NB 32: −1.3 Pla: −3.9 | NB 32: −1.4 Pla: −2.8 | NB 32: +7.1% Pla: +10.0% | NB 32: +9.4%a Pla: +2.8% | NB 32: −16.6%a Pla: −8.5% |
| COR-Diabetes, 201330 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | NB 32/360 mg per day (in 2 doses): 265 Placebo: 159 | NB 32: 106 Pla: 105 | 56 | NB 32: −5.0a Pla: −1.8 | N/A | NB 32: 0 Pla: −1.1 | NB 32: −1.1 Pla: −1.5 | NB 32: −1.4 mg/dL Pla: 0 mg/dL | NB 32: +3.0a mg/dL Pla: −0.3 mg/dL | NB 32: −11.2%a Pla: −0.8% |
| LIGHT, 201631 | BMI ≥27 kg/m2 Diabetes (with hypertension, dyslipidaemia, low HDL, or smoker) | NB 32/360 mg per day (in 2 doses): 4455 Placebo: 4450 | NB 32 mg: 105 Pla: 106 | 208 | NB 32 mg: −3.71a Pla:−1.13 | NB 32: +0.7 Pla: +0.6 | NB 32: +1.4 Pla: +0.5 | N/A | N/A | N/A | N/A |
| Orlistat | |||||||||||
| Chanoine et al, 200532 | Adolescents BMI ≥2 units of 95th percentile (12 years: >28.5 boys, >29.5 girls; 16 years: 31.8 boys, 31.9 girls) Exclude Type 2 diabetes requiring medication | Orl 120 mg (3× day): 352 Placebo: 181 | Orl 120: 98 Pla: 95 | 54 | Orl 120: +0.54a Pla: +3.3 | N/A | Orl 120: +1.09 Pla: +1.31 | Orl 120: −0.51a Pla: +1.30 | Orl 120: −0.99 Pla: +0.88 | Orl 120: +0.07 Pla: −0.31 | Orl 120: +17.9 Pla: +11.68 |
| Sjöström et al., 199833 | BMI ≥28 kg/m2 Exclude Type 2 diabetes requiring medication | Orl 120 mg (3× day): 343 Placebo: 340 | Orl 120: 99 Pla: 100 | 52 | Orl 120: −10.2a Pla: −6.1 | N/A | Orl 120: −6a Pla: −3 | Orl 120: −4.5a Pla: −2.7 | Orl 120: −0.36 mmol/La Pla: −0.04 mmol/L | Orl 120: + 0.07 mmol/L Pla: −0.32 mmol/L | Orl 120: −0.13 mmol/L Pla: −0.13 mmol/L |
| Bariatric surgery | |||||||||||
| STAMPEDE, 201734 | BMI ≥27 kg/m2 HbA1c > 7.0% | GB: 49 SG: 47 MT: 38 | GB: 107 SG: 100 MT: 105 | 260 | GB: −21.7a SG: −18.5a MT: −5.0 | NA | GB: −3.3c SG: −8.4c MT: −4.1 | GB: −5.8c SG: −8.1c MT: −4.4 | GB: +12.4%c SG: +16.6%c MT: +3.7% | GB: +31.9%a SG: +29.6%a MT: +7.0% | GB: −39.8%a SG: −29.4%a MT: −8.3% |
| GATEWAY, 201835 | BMI ≥30 kg/m2 Hypertension No diabetes | GB: 50 MT: 50 | GB: 102 MT: 100 | 52 | GB: −28.9a MT: −0.69 | N/A | GB: +0.8c MT: +5.2 | GB: −0.4c MT: +2.4 | GB: −35.0a MT: −7.4 | GB: +9.8a MT: +1.7 | GB: −81.5a MT: −22.9 |
| Trial . | Population . | Sample size . | Baseline weight (kg) . | Follow-up (weeks) . | Weight loss (%) . | Change in pulse (b.p.m.) . | Change in SBP (mmHg) . | Change in DBP (mmHg) . | Change in LDL . | Change in HDL . | Change in TGs . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Intensive lifestyle intervention | |||||||||||
| Look AHEAD, 201319 | BMI ≥25 kg/m2 Diabetes | ILI: 2570 DSE: 2575 | ILI: 101 DSE: 101 | 499 | ILI: −6.0a DSE: −3.5 | N/A | ILI: −2b DSE: −2 | ILI: −3.7 DSE: −4.5 | ILI: −22.5 mg/dLb DSE: −23.7 mg/dL | ILI: +5.2 mg/dLb DSE: +4.3 mg/dL | ILI: −31 mg/dL DSE: −30 mg/dL |
| Diabetes Prevention Programme, 200220 | BMI ≥24 kg/m2 Pre-diabetes | ILI: 1079 Met: 1073 Pla: 1082 | ILI: 94 Met: 94 Pla: 94 | 146 | ILI: −6.0a Met: −2.1a Pla: −0.1 | N/A | N/A | N/A | N/A | N/A | N/A |
| Liraglutide | |||||||||||
| SCALE Obesity and Prediabetes, 201521 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if untreated weight-related comorbidities present) No Type 2 diabetes | Lira 3.0 mg SQ OD: 2487 Pla: 1244 | Lira 3.0: 106 Pla: 106 | 56 | Lira 3.0: −8.0a Pla: −2.6 | Lira 3.0: +2.5a Pla: 0.1 | Lira 3.0: −4.2a Pla: −1.5 | Lira 3.0: −2.6a Pla: −1.9 | Lira 3.0: −3.0%a Pla: −1.0% | Lira 3.0: +2.3%a Pla: +0.7% | Lira 3.0: −13.3%a Pla: −5.5% |
| SCALE Diabetes, 201522 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | Lira 3.0 mg SQ OD: 423 Lira 1.8 mg SQ OD: 211 Pla: 212 | Lira 3.0: 106 Lira 1.8: 106 Pla: 107 | 56 | Lira 3.0: −6.0a Lira 1.8: −4.7a Pla: −2.0 | N/A | Lira 3.0: −2.8a Lira 1.8: −3.5a Pla: −0.4 | Lira 3.0: −0.9 Lira 1.8: −1.1 Pla: −0.5 | Lira 3.0: −0.6% Lira 1.8: −3.1% Pla: +5.0% | Lira 3.0: +4.7%a Lira 1.8: +4.5% Pla: + 1.9% | Lira 3.0: −14.7%a Lira 1.8: −9.5% Pla: +0.4% |
| Semaglutide | |||||||||||
| STEP 1 trial, 202123 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if untreated weight-related comorbidities present) No Type 2 diabetes | Sema 2.4 mg SQ OW: 1306 Pla: 655 | Sema 2.4: 105 Pla: 105 | 68 | Sema 2.4: −14.9a Pla: −2.4 | Sema 2.4: −3.5a Pla: −0.7 | Sema 2.4: −6.2a Pla: −1.1 | Sema 2.4: −2.8a Pla: −0.4 | Sema 2.4: −3.0%a Pla: +1% | Sema 2.4: +5.0%a Pla: +1% | Sema 2.4: −22.0%a Pla: −7% |
| STEP 2 trial, 202124 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | Sema 2.4 mg SQ OW: 404 Sema 1.0 mg SQ OW: 403 Pla: 403 | Sema 2.4: 100 Sema 1.0: 99 Pla: 101 | 68 | Sema 2.4: −9.64a Sema 1.0: −7.0a Pla: −3.42 | N/A | Sema 2.4: −3.9a Sema 1.0: −2.9a Pla: −0.5 | Sema 2.4: −1.6 Sema 1.0: −0.6 Pla: −0.9 | Sema 2.4: 0% Sema 1.0: −1.0% Pla: 0% | Sema 2.4: +7% Sema 1.0: +5% Pla: +4% | Sema 2.4: −22%a Sema 1.0: −17%a Pla: −9% |
| STEP 3 trial, 202125 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | Sema 2.4 mg SQ OW: 407 Pla: 204 | Sema 2.4: 107 Pla: 104 | 68 | Sema 2.4: −16.0a Pla: −5.7 | N/A | Sema 2.4: −5.6a Pla: −1.6 | Sema 2.4: −3.0a Pla: −0.8 | Sema 2.4: −4.7%a Pla: +2.6% | Sema 2.4: +6.5% Pla: +5.0% | Sema 2.4: −22.5%a Pla: −6.5% |
| Tirzepatide | |||||||||||
| SURMOUNT-1, 202226 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | Tirze 5 mg SQ OW: 630 Tirze 10 mg SQ OW: 636 Tirze 15 mg SQ OW: 630 Pla: 643 | Tirze 5: 103 Tirze 10: 106 Tirze 15: 106 Pla: 105 | 72 | Tirze 5: −15.0a Tirze 10: −19.5a Tirze 15: −20.9a Pla: −3.1 | Tirze: +1.8a Pla: +0.1 | Tirze: −7.2a Pla: −1.0 | Tirze: −4.8a Pla: −0.8 | Tirze: −5.8%a Pla: −1.7% | Tirze: +8.0%a Pla: −0.7% | Tirze: −24.8%a Pla: −5.6% |
| Naltrexone/bupropion | |||||||||||
| COR-I, 201027 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 583 NB 16/360 mg per day (in 2 doses): 578 Placebo: 581 | NB 32: 100 NB 16: 100 Pla: 100 | 56 | NB 32: −6.1a NB 16: −Pla: −1.3 | NB 32: +0.4a NB 16: +1.1a Pla: −1.0 | NB 32: −0.1a NB 16: +0.3a Pla: −1.9 | NB 32: 0.0a NB 16: +0.1a Pla: −0.9 | NB 32: −2.0%a NB 16: −1.5%a Pla: −0.5% | NB 32: +8.0%a NB 16: +7.6%a Pla: +0.8% | NB 32: −12.7%a NB 16: −8.0%a Pla: −3.1% |
| COR-II, 201328 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 1001 Placebo: 495 | NB 32: 100 Pla: 99 | 56 | NB 32: −6.4a Pla: −1.2 | NB 32: +0.8a Pla: −0.3 | NB 32: +0.6a Pla: −0.5 | NB 32: +0.4 Pla: +0.3 | NB 32: −6.2 mg/dLa Pla: −2.1 mg/dL | NB 32: +3.6 mg/dLa Pla: −0.9 mg/dL | NB 32: −9.8%a Pla: −0.5% |
| COR-BMOD, 201129 | BMI ≥30 kg/m2 (or ≥27 kg/m2 if weight-related comorbidities present) No Type 2 diabetes | NB 32/360 mg per day (in 2 doses): 591 Placebo: 202 | NB 32: 102 Pla: 100 | 56 | NB 32: −9.3a Pla: −5.1 | NB 32: +1.1 Pla: +0.2 | NB 32: −1.3 Pla: −3.9 | NB 32: −1.4 Pla: −2.8 | NB 32: +7.1% Pla: +10.0% | NB 32: +9.4%a Pla: +2.8% | NB 32: −16.6%a Pla: −8.5% |
| COR-Diabetes, 201330 | BMI ≥27 kg/m2 HbA1c 7.0%–10.0% | NB 32/360 mg per day (in 2 doses): 265 Placebo: 159 | NB 32: 106 Pla: 105 | 56 | NB 32: −5.0a Pla: −1.8 | N/A | NB 32: 0 Pla: −1.1 | NB 32: −1.1 Pla: −1.5 | NB 32: −1.4 mg/dL Pla: 0 mg/dL | NB 32: +3.0a mg/dL Pla: −0.3 mg/dL | NB 32: −11.2%a Pla: −0.8% |
| LIGHT, 201631 | BMI ≥27 kg/m2 Diabetes (with hypertension, dyslipidaemia, low HDL, or smoker) | NB 32/360 mg per day (in 2 doses): 4455 Placebo: 4450 | NB 32 mg: 105 Pla: 106 | 208 | NB 32 mg: −3.71a Pla:−1.13 | NB 32: +0.7 Pla: +0.6 | NB 32: +1.4 Pla: +0.5 | N/A | N/A | N/A | N/A |
| Orlistat | |||||||||||
| Chanoine et al, 200532 | Adolescents BMI ≥2 units of 95th percentile (12 years: >28.5 boys, >29.5 girls; 16 years: 31.8 boys, 31.9 girls) Exclude Type 2 diabetes requiring medication | Orl 120 mg (3× day): 352 Placebo: 181 | Orl 120: 98 Pla: 95 | 54 | Orl 120: +0.54a Pla: +3.3 | N/A | Orl 120: +1.09 Pla: +1.31 | Orl 120: −0.51a Pla: +1.30 | Orl 120: −0.99 Pla: +0.88 | Orl 120: +0.07 Pla: −0.31 | Orl 120: +17.9 Pla: +11.68 |
| Sjöström et al., 199833 | BMI ≥28 kg/m2 Exclude Type 2 diabetes requiring medication | Orl 120 mg (3× day): 343 Placebo: 340 | Orl 120: 99 Pla: 100 | 52 | Orl 120: −10.2a Pla: −6.1 | N/A | Orl 120: −6a Pla: −3 | Orl 120: −4.5a Pla: −2.7 | Orl 120: −0.36 mmol/La Pla: −0.04 mmol/L | Orl 120: + 0.07 mmol/L Pla: −0.32 mmol/L | Orl 120: −0.13 mmol/L Pla: −0.13 mmol/L |
| Bariatric surgery | |||||||||||
| STAMPEDE, 201734 | BMI ≥27 kg/m2 HbA1c > 7.0% | GB: 49 SG: 47 MT: 38 | GB: 107 SG: 100 MT: 105 | 260 | GB: −21.7a SG: −18.5a MT: −5.0 | NA | GB: −3.3c SG: −8.4c MT: −4.1 | GB: −5.8c SG: −8.1c MT: −4.4 | GB: +12.4%c SG: +16.6%c MT: +3.7% | GB: +31.9%a SG: +29.6%a MT: +7.0% | GB: −39.8%a SG: −29.4%a MT: −8.3% |
| GATEWAY, 201835 | BMI ≥30 kg/m2 Hypertension No diabetes | GB: 50 MT: 50 | GB: 102 MT: 100 | 52 | GB: −28.9a MT: −0.69 | N/A | GB: +0.8c MT: +5.2 | GB: −0.4c MT: +2.4 | GB: −35.0a MT: −7.4 | GB: +9.8a MT: +1.7 | GB: −81.5a MT: −22.9 |
SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; BMI, body mass index; Look AHEAD, Action for Health in Diabetes; ILI, intensive lifestyle intervention; DSE, diabetes support and education; Met, metformin; Pla, placebo; N/A, not available; SCALE, Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities; Lira, liraglutide; STEP, Semaglutide Treatment Effect in People with Obesity; Sema, semaglutide; SURMOUNT, A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight; Tirze, Tirzepatide; DP, diethylpropion; NB, naltrexone/bupropion; COR, A Study of the Safety and Efficacy of Two Doses of Naltrexone SR/Bupropion SR and Placebo in Overweight and Obese Subjects; NB, Naltrexone/bupropion; LIGHT, Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors; Orl, orlistat; STAMPEDE, Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently; GB, Gastric bypass; SG, sleeve gastrectomy; MT, medical therapy; GATEWAY, Gastric Bypass to Treat Obese Patients With Steady Hypertension.
aP < .05 for intervention vs. control.
bAlthough values for these parameters were similar between the ILI and DSE groups at the end of the trial, a significant improvement was noted with ILI on average over the entire trial period.
cA significant benefit of the intervention on this parameter was not observed likely due to lower anti-hypertensive/anti-lipidaemic drug use in the intervention arm/anti-lipidaemic drug use in the intervention arm.
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