Table 1.
Trial Data Investigating the Use of Glucagon‐Like Peptide‐1 Receptor Agonists for the Treatment of Obesity
| Study | Study design and population | Treatment arms | Baseline data, mean, overall | Changes in end points during the randomization period, active trial drug vs placebo |
|---|---|---|---|---|
| SCALE Obesity and Prediabetes 68 | 56‐week, double‐blind, randomized placebo‐controlled trial in people with obesity/overweight and without T2D | Once‐daily subcutaneous liraglutide 3.0 mg (n=2487) vs placebo (n=1244) |
Body weight, 106.2 kg BMI, 38.3 mg/kg2 WC, ≈115 cm Systolic BP, ≈123 mm Hg Diastolic BP, ≈78.8 mm Hg Total cholesterol, ≈194 mg/dL Triglycerides, ≈127 mg/dL |
Body weight, % change: −8.0 vs −2.6 (ETD: −5.4 [95% CI, –5.8 to −5.0]), P<0.001 BMI, mg/kg2: −3.0% vs −1.0% (ETD: −2.0 [95% CI, −2.2 to −1.9], P<0.001) WC, cm: −8.2 vs −3.9 (ETD: −4.2 [95% C, −4.7 to −3.7], P<0.001) Systolic BP, mm Hg: −4.2 vs −1.5 (ETD: −2.8 [95% CI, −3.56 to −2.09], P<0.001) Diastolic BP, mm Hg: −2.6 vs −1.9 (ETD: −0.9 [95% CI, −1.41 to −0.37], P<0.001) Total cholesterol, mg/dL: −3.1% vs −1.0% (ETD: −2.3 [95% CI, −3.3 to −1.3], P<0.001) Triglycerides, mg/dL: −13.3% vs −5.5% (ETD: −9.3 [95% CI, −11.5 to −7.0], P<0.001) |
| SCALE Diabetes 67 | 56‐week, double‐blind, randomized placebo‐controlled trial in people with obesity/overweight and T2D | Once‐daily subcutaneous liraglutide 3.0 mg (n=423) vs liraglutide 1.8 mg (n=211) vs placebo (n=212) |
Body weight, ≈106 kg BMI, ≈37 mg/kg2 WC, ≈118 cm Systolic BP, ≈129 mm Hg Diastolic BP, ≈79 mm Hg Total cholesterol, ≈169–≈178 mg/dL Triglycerides, 158–170 mg/dL |
Body weight, % change: −6.0 vs −2.0 (ETD for liraglutide 3.0 mg vs placebo: −4.00 [95% CI, –5.10 to −2.90], P<0.001) BMI, mg/kg2: −2.2% vs −0.8% (ETD for liraglutide 3.0 mg vs placebo: −1.50 [95% CI, –1.83 to −1.18], P<0.001) WC, cm: −6.1 vs −2.7 (ETD for liraglutide 3.0 mg vs placebo: −3.22 [95% CI, –4.20 to −2.23], P<0.001) Systolic BP, mm Hg: −2.8 vs −0.4 (ETD for liraglutide 3.0 mg vs placebo: −2.59 [95% CI, –4.56 to −0.62], P=0.01) Diastolic BP, mm Hg: −0.9 vs −0.5 (ETD for liraglutide 3.0 mg vs placebo: −0.36 [95% CI, –1.69 to 0.96], P=0.59) Total cholesterol, geometric mean (CoV), %: −1.46 vs 3.8 (ETD for liraglutide 3.0 mg vs placebo: 0.96 [95% CI, 0.94 to 0.99], P=0.01) Triglycerides, geometric mean (CoV), %: −14.68 vs 0.41 (ETD for liraglutide 3.0 mg vs placebo: 0.86 [95% CI, 0.80 to 0.92], P<0.001) |
| SCALE Maintenance 69 | 56‐week, double‐blind, randomized placebo‐controlled trial in people with obesity or overweight (with comorbidities), without T2D who lost ≥5% of initial weight during a low‐calorie diet run‐in | Once‐daily subcutaneous liraglutide 3.0 mg (n=212) vs placebo (n=210) |
Body weight, ≈106 kg BMI, ≈38 mg/kg2 WC, ≈113.5 cm Systolic BP, ≈123 mm Hg Diastolic BP, 78.5 mm Hg Total cholesterol, ≈5.0 mmol/L Triglycerides, ≈1.55 mmol/L |
Body weight, % change: −6.2 vs −0.2 (ETD: −6.1 [95% CI, −7.5 to −4.6], P<0.0001) BMI, mg/kg2: −2.1% vs −0.0% (ETD: −2.1 [95% CI, –2.5 to −1.6], P<0.0001) WC, cm: −4.7 vs −1.2 (ETD: −3.5 [95% CI, –4.8 to −2.2], P<0.0001) Systolic BP, mm Hg: 0.2 vs 2.8 (ETD: −2.7 [95% CI, –4.7 to −0.8], P=0.007) Diastolic BP, mm Hg: 1.4 vs 1.2 (ETD: −0.3 [95% CI –1.7 to 1.1], P=0.64) Total cholesterol, mg/dL: 0.2% vs 0.3% (ETD: −0.1 [95% CI, –0.2 to 0.03], P=0.11) Triglycerides, mg/dL: 0% vs 0.1% (ETD: −0.11 [95% CI, –0.20 to −0.01], P=0.03) |
| STEP 1 71 | 68‐week double‐blind, randomized placebo‐controlled trial in people with overweight (plus at least 1 untreated weight‐related comorbidity) or obesity, without T2D | Once‐weekly subcutaneous semaglutide 2.4 mg (n=1306) vs placebo (n=655) |
Body weight, ≈105 kg BMI, ≈38 mg/kg2 WC, ≈115 cm Systolic BP, ≈126 mm Hg Diastolic BP, 80 mm Hg Total cholesterol, ≈190–≈192 mg/dL Triglycerides, 126–128 mg/dL |
Body weight, % change: −14.9% vs −2.4% (ETD: −12.4%‐points [95% CI, –13.4 to −11.5], P<0.001) BMI, mg/kg2: −5.5 vs −0.9 (ETD: −4.6 [95% CI, –5.0 to −4.3]) WC, cm: −13.54 vs −4.13 (ETD: −9.42 [95% CI, –10.30 to −8.53], P<0.001) Systolic BP, mm Hg: −6.16 vs −1.06, (ETD: −5.10 [95% CI, –6.34 to −3.87], P<0.001) Diastolic BP, mm Hg: −2.83 vs −0.42 (ETD: −2.41 [95% CI, –3.25 to −1.57]) Total cholesterol, ratio of week 68 to baseline: 0.97 vs 1.00 (ETD: 0.97 [95% CI, 0.95 to 0.98]) Triglycerides, ratio of week 68 to baseline: 0.78 vs 0.93 (ETD: 0.84 [95% CI, 0.81 to 0.87]) |
| STEP 2 72 | 68‐week double‐blind, randomized placebo‐controlled trial in people with obesity/overweight and T2D | Once‐weekly subcutaneous semaglutide 2.4 mg (n=404) vs semaglutide 1.0 mg (n=403) vs placebo (n=403) |
Body weight, 99.8 kg BMI, 35.7 mg/kg2 WC, 114.6 cm Systolic BP, 130 mm Hg Diastolic BP, 80 mm Hg Total cholesterol, 4.4 mmol/L Triglycerides, 1.8 mmol/L |
Body weight, % change: −9.64% vs −6.99% vs −3.42% (placebo) (ETD for semaglutide 2.4 mg vs placebo: −6.21 [95% CI, −7.28 to −5.15], P<0.0001) BMI, mg/kg2: −3.5 vs −2.5 vs −1.3 (ETD for semaglutide 2.4 mg vs placebo: −2.3 [95% CI, −2.6 to −1.9]) WC, cm: −9.4 vs −6.7 vs −4.5 (ETD for semaglutide 2.4 mg vs placebo: −4.9 [95% CI, −6.0 to −3.8]; P<0.0001) Systolic BP, mm Hg: −3.9 vs −2.9 vs −0.5 (ETD for semaglutide 2.4 mg vs placebo: −3.4 [95% CI, –5.6 to −1.3], P=0.0016) Diastolic BP, mm Hg: −1.6 vs −0.6 vs −0.9 (ETD for semaglutide 2.4 mg vs placebo: −0.7 [95% CI, −2.0 to 0.6]) Total cholesterol, ratio of week 68 to baseline: 0.99 vs 0.98 vs 0.99 (ETR for semaglutide 2.4 mg vs placebo: 0.99 [95% CI, 0.96 to 1.02]) Triglycerides, ratio of week 68 to baseline: 0.78 vs 0.83 vs 0.91 (ETR for semaglutide 2.4 mg vs placebo: 0.86 [95% CI, 0.81 to 0.92]) |
| STEP 3 73 | 68‐week double‐blind, randomized placebo‐controlled trial in people with overweight (plus at least 1 weight‐related comorbidity) or obesity, without diabetes, combined with intensive behavioral therapy | Once‐weekly subcutaneous semaglutide 2.4 mg (n=407) vs placebo (n=204) |
Body weight, ≈107–≈104 kg BMI, ≈38 mg/kg2 WC, ≈113 cm Systolic BP, ≈124 mm Hg Diastolic BP, ≈80 mm Hg Total cholesterol, ≈185 – ≈189 mg/dL Triglycerides, 108–111 mg/dL |
Body weight, % change: −16.0 vs −5.7 (ETD: −10.3 [95% CI, –12.0 to −8.6], P<0.001) BMI, mg/kg2: −6.0 vs −2.2 (ETD: −3.8 [95% CI, –4.4 to −3.1], P<0.001) WC, cm: −14.6 vs −6.3 (ETD: −8.3 [95% CI, –10.1 to −6.6], P<0.001) Systolic BP, mm Hg: −5.6 vs −1.6 (ETD: −3.9 [95% CI, –6.4 to −1.5], P=0.001) Diastolic BP, mm Hg: −3.0 vs −0.8 (ETD: −2.2 [95% CI, –3.9 to −0.6], P=0.008) Total cholesterol, % change at week 68: −3.8 vs 2.1 (ETD: −5.8 [95% CI, –8.4 to −3.2], P<0.001) Triglycerides, % change at week 68: −22.5 vs −6.5 (ETD: −17.0 [95% CI, –22.8 to −10.8], P<0.001) |
| STEP 4 74 | 68‐wk double‐blind, randomized placebo‐controlled trial evaluating sustained weight loss in people with overweight (plus at least 1 weight‐related comorbidity) or obesity, without diabetes | 20‐wk run‐in: once‐weekly subcutaneous semaglutide 2.4 mg (n=902); 48‐week randomized period: once‐weekly subcutaneous semaglutide 2.4 mg (n=535) vs placebo (n=268) |
Body weight, 107.2 kg BMI, 38.4 mg/kg2 WC, 115.3 cm Systolic BP, 127 mm Hg Diastolic BP, 81 mm Hg Total cholesterol, 194.6 mg/dL Triglycerides, 117.5 mg/dL |
Body weight, % change: −7.9 vs 6.9 (ETD: −14.8 [95% CI, −16.0 to −13.5], P<0.001) BMI, mg/kg2: −2.6 vs 2.2 (ETD: −4.7 [95% CI, −5.2 to −4.3], P<0.001) WC, cm: −6.4 vs 3.3 (ETD: −9.7 [95% CI, −10.9 to −8.5], P<0.001) Systolic BP, mm Hg: 0.5 vs 4.4 (ETD: −3.9 [95% CI, −5.8 to −2.0], P<0.001) Diastolic BP, mm Hg 0.3 vs 0.9 (ETD: −0.6 [95% CI, −2.0 to 0.9], P=0.46) Total cholesterol, % change: 5 vs 11 (ETD: −6 [95% CI, −8 to −4], P<0.001) Triglycerides, % change: −6 vs 15, (ETD: −18 [95% CI, −24 to −11], P<0.001) |
| SURMOUNT‐1 78 | 72‐wk double‐blind, randomized placebo‐controlled trial in people with overweight (plus at least 1 weight‐related comorbidity) or obesity, without diabetes | Once‐weekly subcutaneous tirzepatide 5 mg (n=630) vs tirzepatide 10 mg (n=636) vs tirzepatide 15 mg (n=630) vs placebo (n=643) |
Body weight, 104.8 kg BMI, 38 mg/kg2 WC, 114.1 cm Systolic BP, 123.3 mm Hg Diastolic BP, 79.5 mm Hg Total cholesterol, 187.9 mg/dL Triglycerides, 128.4 mg/dL |
Body weight, % change: −15.0 (5 mg; ETD: −11.9% points [95% CI, −13.4 to −10.4]) vs −19.5 (10 mg; ETD: −16.4% points [95% CI, −17.9 to −14.8]) vs −20.9 (15 mg; ETD: −17.8% points [95% CI, −19.3 to −16.3]) vs −3.1 (placebo) WC, cm: −14.0 (5 mg; ETD: −10.1 [95% CI, −1.6 to −8.6]) vs −17.7 (10 mg; ETD: −13.8 [95% CI, −15.2 to −12.3]) vs −18.5 (15 mg; ETD: −14.5 [95% CI −15.9 to −13.0]) vs −4.0 (placebo) Systolic BP, mm Hg: † −7.2 vs −1.0 (ETD: −6.2 [95% CI, −7.7 to −4.8]) Diastolic BP, mm Hg: † −4.8 vs −0.8 (ETD: −4.0 [95% CI, −4.9 to −3.1]) Total cholesterol, mg/dL: † −4.8 vs −1.8 (ETD: −3.1 [95% CI, −5.2 to −1.0]) Triglycerides, mg/dL: † −24.8 vs −5.6 (ETD: −20.3 [95% CI, −24.3 to −16.1]) All comparisons for tirzepatide vs placebo were significant at P<0.001 |
BP indicates blood pressure; BMI, body mass index; CoV, coefficient of variation; ETD, estimated treatment difference; ETR, estimated treatment ratio; SCALE, Satiety and Clinical Adiposity – Liraglutide Evidence in individuals with and without diabetes; STEP 1, Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity; STEP 2, Research Study Investigating How Well Semaglutide Works in People With Type 2 Diabetes Suffering From Overweight or Obesity; STEP 3, Research Study to Look at How Well Semaglutide is at Lowering Weight When Taken Together With an Intensive Lifestyle Program; SURMOUNT‐1, Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity (STEP 4); A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight; T2D, type 2 diabetes; and WC, waist circumference.
Where pooled data for all study groups were not given in the original publication, the data have been rounded/approximated for convenience so as to be illustrative of the overall study cohorts.
Pooled data for the 5‐mg, 10‐mg, and 15‐mg tirzepatide groups vs placebo.