Table 2.
RCTs of GLP1-RAs use in Obesity.
| Trial name or authors | Number of patients | Duration | Inclusion criteria | Change in weight (%) | Other information |
|---|---|---|---|---|---|
| GLP-1 RA | |||||
| SCALE Obesity and Prediabetesa,37 | Total = 3731 Liraglutide 3.0 mg = 2487 Placebo = 1244 |
56 weeks | ≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥27 kg/m2 with at least one weight-related condition, without diabetes | Liraglutide 3.0 mg = −8.0% Placebo = −2.6% |
Bodyweight reduction threshold (≥5%; ≥10%): Liraglutide 3.0 mg = 63%; 33% Placebo = 27%; 10% |
| Wadden et al.a38 | Total = 150 IBT alone: 50 IBT + Liraglutide 3.0 mg: 50 Multicomponentb: 50 |
52 weeks | 21–70-year-old adults with at least one unsuccessful weight loss attempt, and a BMI between 30 and 55 kg/m2, without diabetes | At week 24: IBT alone: −5.4% IBT + Liraglutide 3.0 mg: −10.1% Multicomponentb: −12.2% At week 52: IBT alone: −6.1% IBT + Liraglutide 3.0 mg: −11.5% Multicomponentb: −11.8% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%): At week 24: IBT alone: 46%; 20%; 6% IBT + Liraglutide 3.0 mg: 78%; 46%; 20% Multicomponenta: 82%; 60%; 32% At week 52: IBT alone: 44%; 26%; 12% IBT + Liraglutide 3.0 mg: 70%; 46%; 28% Multicomponenta: 74%; 52%; 36% |
| SCALE Teensa39 | Total = 251 Liraglutide 3.0 mg = 125 Placebo = 126 |
82 weeks: 56 weeks (liraglutide or placebo) + 26 weeks (follow-up without treatment) |
12–18-year-old adolescents with at least one unsuccessful weight loss attempt, and a BMI in the 95th percentile or higher (according to sex and age-specific growth charts), including T2DM | At week 56: Liraglutide 3.0 mg = −3.2% Placebo = +2.2% At week 82: Liraglutide 3.0 mg = +1.5% Placebo = +4.6% |
BMI reduction threshold at week 56 (≥5%; ≥10%): Liraglutide 3.0 mg = 43%; 26% Placebo = 19%; 8% Changes in BMI at week 56 (%): Liraglutide 3.0 mg = −4.3% Placebo = +0.3% |
| SCALE IBTa40 | Total = 282 IBT + Liraglutide 3.0 mg = 142 IBT + Placebo = 140 |
56 weeks | ≥18-year-old adults with a BMI ≥ 30 kg/m2, without diabetes | IBT + Liraglutide 3.0 mg = −7.5% IBT + Placebo = −4.0% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%): IBT + Liraglutide 3.0 mg = 61%; 30%; 18% IBT + Placebo = 39%; 20%; 9% |
| Neeland et al.a41 | Total = 128 Liraglutide 3.0 mg = 73 Placebo = 55 |
40 weeks | ≥35-year-old adults with a BMI ≥ 30 kg/m2 or ≥27 kg/m2 with metabolic syndrome, without diabetes | Liraglutide 3.0 mg = −6.6% Placebo = −1.2% |
Bodyweight reduction threshold (≥5%; ≥10%): Liraglutide 3.0 mg = 63%; 19% Placebo = 22%; 3% Visceral adipose tissue changes: Liraglutide 3.0 mg = −12.5% Placebo = −1.6% |
| Lundgren et al.a42 | Total = 195 Liraglutide 3.0 mg = 49 Exercise = 48 Liraglutide 3.0 mg + exercise = 49 Placebo = 49 |
60 weeks: 8 weeks of low-calorie diet + 52 weeks of treatment (randomization) |
18–65-year-old adults with a BMI between 32 and 43 kg/m2, without diabetes | From week −8 to 52: Liraglutide 3.0 mg = −13.4% Exercise = −10.9% Liraglutide 3.0 mg + exercise = −15.7% Placebo = −6.7% |
Bodyweight reduction threshold from week −8 to 52 (≥5%; ≥10%; ≥15%; ≥20%): Liraglutide 3.0 mg = 88%; 59%; 29%; 22% Exercise = 80%; 45%; 30%; 18% Liraglutide 3.0 mg + exercise = 87%; 69%; 49%; 33% Placebo = 70%; 28%; 10%; 2% |
| STEP 1a40 | Total = 1961 Semaglutide 2.4 mg = 1306 Placebo = 655 |
68 weeks | ≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥27 kg/m2 with at least one weight-related condition, without diabetes | Semaglutide 2.4 mg = −14.9% Placebo = −2.4% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%; ≥20%): Semaglutide 2.4 mg = 86%; 69%; 50%; 32% Placebo = 31%; 12%; 5%; 2% |
| STEP 2a40 | Total = 1210 Semaglutide 1.0 mg = 403 Semaglutide 2.4 mg = 404 Placebo = 403 |
68 weeks | ≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 27 kg/m2, and T2DM | Semaglutide 1.0 mg = −6.9% Semaglutide 2.4 mg = −9.6% Placebo = −3.4% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%; ≥20%): Semaglutide 1.0 mg = 57%; 28%; 14%; 5% Semaglutide 2.4 mg = 69%; 45%; 26%; 13% Placebo = 28%; 8%; 3%; 1% |
| STEP 3a40 | Total = 611 IBT + Semaglutide 2.4 mg = 407 IBT + Placebo = 204 |
68 weeks | ≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥27 kg/m2 with at least one weight-related condition, without diabetes | Semaglutide 2.4 mg = −16.0% Placebo = −5.7% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%; ≥20%): Semaglutide 2.4 mg = 86%; 75%; 56%; 36% Placebo = 47%; 27%; 13%; 4% |
| STEP 4a40 | Semaglutide 2.4 (week 0–20) = 803 Semaglutide 2.4 mg (week 20–68) = 535 Placebo (week 20–68) = 268 |
68 weeks: 20 weeks (semaglutide open-label) + 48 weeks (semaglutide or placebo) |
≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥27 kg/m2 with at least one weight-related condition, without diabetes | From week 0–20 Semaglutide 2.4 = −10.6% From week 20–68: Semaglutide 2.4= −7.9% Placebo = +6.9% |
Bodyweight reduction threshold from week 0–68 (≥5%; ≥10%; ≥15%; ≥20%): Semaglutide 2.4 mg = 89%; 79%; 64%; 39% Placebo = 47%; 20%; 9%; 5% |
| STEP 5a40 | Total = 304 Semaglutide 2.4 mg = 152 Placebo = 152 |
104 weeks | ≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥27 kg/m2 with at least one weight-related condition, without diabetes | Semaglutide 2.4 mg = −15.2% Placebo = −2.6% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%; ≥20%): Semaglutide 2.4 mg = 77%; 62%; 52%; 36% Placebo = 34%; 13%; 7%; 2% |
| STEP 5 (Control of eating)a43 | Total = 174 Semaglutide 2.4 mg = 88 Placebo = 86 |
104 weeks | ≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥27 kg/m2 with at least one weight-related condition, without diabetes | Semaglutide 2.4 mg = −14.8% Placebo = −2.4% |
Significant improvement of semaglutide compared to placebo: Craving control, craving for savory foods, difficulty in resisting cravings, and difficulty controlling eating at weeks 20, 52, and 104; Positive mood and craving for sweet foods at weeks 20 and 52; Hunger and feelings of fullness at week 20. |
| STEP 6a32 | Total = 401 Semaglutide 1.7 mg = 101 Semaglutide 2.4 mg = 199 Placebo = 101 |
68 weeks | East Asian (Japan and South Korea) ≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 35 kg/m2 with at least one weight-related comorbidity or ≥27 kg/m2 with at least two weight-related comorbidities. At least one comorbidity had to be hypertension or dyslipidemia, or, in Japan only, T2DM | Semaglutide 1.7 mg = −9.6% Semaglutide 2.4 mg = −13.2% Placebo = −2.1% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%; ≥20%): Semaglutide 1.7 mg = 72%; 42%; 24%; 11% Semaglutide 2.4 mg = 83%; 61%; 41%; 20% Placebo = 21%; 5%; 3%; 2% |
| STEP 8a40 | Total = 338 Semaglutide 2.4 mg = 126 Liraglutide 3.0 mg = 127 Placebo = 85 |
68 weeks | ≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with at least one weight-related condition, without diabetes | Semaglutide 2.4 mg = −15.8% Liraglutide 3.0 mg = −6.4% Placebo = −1.9% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%; ≥20%): Semaglutide 2.4 mg = 87%; 71%; 55%; 38% Liraglutide 3.0 mg = 58%; 25%; 12%; 6% Placebo = 29%; 15%; 6%; 2% |
| STEP TEENSa40 | Total = 201 Semaglutide 2.4 mg = 134 Placebo = 67 |
68 weeks | 12–18-year-old adolescents with at least one unsuccessful weight loss attempt, a BMI in the 95th percentile or higher (according to sex and age-specific growth charts), or in the 85th percentile or higher with at least one weight-related condition, including T2DM | Semaglutide 2.4 mg = −14.7% Placebo = +2.7% |
BMI reduction threshold (≥5%; ≥10%; ≥15%; ≥20%): Semaglutide 2.4 mg = 76%; 63%; 57%; 40% Placebo = 23%; 10%; 5%; 3% Changes in BMI (%): Semaglutide 2.4 mg = −16.1% Placebo = +0.6% |
| OASIS 1a44 | Total = 667 Semaglutide 50 mg (oral) = 334 Placebo = 333 |
68 weeks | ≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with at least one weight-related condition, without diabetes | Semaglutide 50 mg = −15.1% Placebo = −2.4% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%; ≥20%): Semaglutide 50 mg = 85%; 69%; 54%; 34% Placebo = 26%; 12%; 6%; 3% |
| STEP-HFpEF45 | Total = 529 Semaglutide 2.4 mg = 263 Placebo = 266 |
52 weeks | ≥18-year-old adults with a left ventricular ejection fraction of at least 45%, a BMI ≥ 30 kg/m2, New York Heart Association functional class II, III, or IV, a Kansas City Cardiomyopathy Questionnaire clinical summary score of less than 90 points, and a 6-min walk distance of at least 100 m, without diabetes | Semaglutide 2.4 mg = −13.3% Placebo = −2.6% |
Bodyweight reduction threshold (≥10%; ≥15%; ≥20%): Semaglutide 2.4 mg = 66%; 44%; 23% Placebo = 9%; 2%; 0% |
| SELECT46 | Total = 17,604 Semaglutide 2.4 mg = 8803 Placebo = 8801 |
∼40 months | ≥45-year-old adults with a BMI ≥ 27 kg/m2 with established cardiovascular disease, without diabetes | Semaglutide 2.4 mg = −9.4% Placebo = −0.9% |
Primary cardiovascular end-point event: Semaglutide 2.4 mg = 6.5% Placebo = 8.0% |
| GZGIa29 | Total = 272 Orforglipron 12 mg = 50 Orforglipron 24 mg = 53 Orforglipron 36 mg = 58 Orforglipron 45 mg = 61 Placebo = 50 |
36 weeks | 18–75-year-old adults with a BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with at least one weight-related condition, without diabetes | At week 26 Orforglipron 12 mg = −8.6% Orforglipron 24 mg = −11.2% Orforglipron 36 mg = −12.3% Orforglipron 45 mg = −12.6% Placebo = −2.0% At week 36 Orforglipron 12 mg = −9.4% Orforglipron 24 mg = −12.5% Orforglipron 36 mg = −13.5% Orforglipron 45 mg = −14.7% Placebo = −2.3% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%): By week 26 Orforglipron 12 mg = 74%; 39%; 21% Orforglipron 24 mg = 89%; 57%; 26% Orforglipron 36 mg = 90%; 71%; 34% Orforglipron 45 mg = 87%; 70%; 34% Orforglipron Placebo = 23%; 2%; 0% By week 36 Orforglipron 12 mg = 72%; 46%; 22% Orforglipron 24 mg = 90%; 62%; 33% Orforglipron 36 mg = 92%; 75%; 43% Orforglipron 45 mg = 90%; 69%; 48% Placebo = 24%; 9%; 1% |
| Dual (GLP-1/GIP or GLP-1/glucagon) RA | |||||
| SURMOUNT-1a47 | Total = 2539 Tirzepatide 5 mg = 630 Tirzepatide 10 mg = 636 Tirzepatide 15 mg = 630 Placebo = 643 |
72 weeks | ≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with at least one weight-related condition, without diabetes | TZP 5 mg = −15.0% TZP 10 mg = −19.5% TZP 15 mg = −20.9% Placebo = −3.1% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%; ≥20%; ≥25%): TZP 5 mg = 85%; 68%; 48%; 30%; 15% TZP 10 mg = 89%; 78%; 66%; 50%; 32% TZP 15 mg = 91%; 83%; 70%; 56%; 36% Placebo = 34%; 19%; 9%; 3%; 1% |
| SURMOUNT-248 | Total = 938 Tirzepatide 10 mg = 312 Tirzepatide 15 mg = 311 Placebo = 315 |
72 weeks | ≥18-year-old adults with a BMI ≥ 27 kg/m2 with at least one weight-related condition, including diabetes | Tirzepatide 10 mg = −12.8% Tirzepatide 15 mg = −14.7% Placebo = −3.2% |
Bodyweight reduction threshold (≥5%; ≥10%; ≥15%; ≥20%; ≥25%): Tirzepatide 10 mg = 79%; 60%; 39%; 21%; 9% Tirzepatide 15 mg = 83%; 65%; 48%; 31%; 15% Placebo = 32%; 9%; 3%; 1%; 0% |
| SURMOUNT-3a40 | Total = 579 ILI + Tirzepatide MTD = 287 ILI + placebo = 292 |
84 weeks: 12 weeks of ILI + 72 weeks (Tirzepatide or placebo) |
≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with at least one weight-related condition, without diabetes | 72 weeks with Tirzepatide: Tirzepatide = −18.4% Placebo = +2.5% 84 weeks (12 weeks of lLI + 72 weeks of tirzepatide or placebo): Tirzepatide = −24.3% Placebo = −4.5% |
Bodyweight reduction threshold, from randomization to week 72 (≥5%; ≥10%; ≥15%; ≥20%; ≥25%): Tirzepatide = 87%; 77%; 65%; 45%; 29% Placebo = 16%; 9%; 4%; 2%; 1% |
| SURMOUNT-4a49 | Total = 670 Tirzepatide MTD = 335 Placebo = 335 |
88 weeks: 36 weeks of open-label Tirzepatide + 52 weeks (Tirzepatide or placebo) |
≥18-year-old adults with at least one unsuccessful weight loss attempt, a BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with at least one weight-related condition, without diabetes | At week 36 Tirzepatide = −20.9% From week 36–88 Tirzepatide = −5.5% Placebo = +14.0% |
Bodyweight reduction threshold, from week 0–88 (≥5%; ≥10%; ≥15%; ≥20%; ≥25%): Tirzepatide = 97%; 92%; 84%; 69%; 54% Placebo = 70%; 46%; 26%; 12%; 5% |
| le Roux et al.a50 | Total = 384 Survodutide 0.6 mg = 77 Survodutide 2.4 mg = 78 Survodutide 3.6 mg = 76 Survodutide 4.8 mg = 76 Placebo = 77 |
46 weeks | 18–75-year-old adults with at least one unsuccessful weight loss attempt, a BMI of 27 kg/m2 or greater, without diabetes | Survodutide 0.6 mg = −6.2 Survodutide 2.4 mg = −12.5 Survodutide 3.6 mg = −13.2% Survodutide 4.8 mg = −14.9% Placebo = −2.8% |
Bodyweight reduction threshold at week 46 (≥5%; ≥10%; ≥15%; ≥20%): Survodutide 0.6 mg = 60%; 34%; 12%; 0% Survodutide 2.4 mg = 81%; 65%; 38%; 21% Survodutide 3.6 mg = 82%; 65%; 46%; 30% Survodutide 4.8 mg = 83%; 69%; 55%; 33% Placebo = 26%; 11%; 5%; 0% |
| Ji et al.51 | Total = 248 Mazdutide 3.0 mg = 62 Mazdutide 4.5 mg = 63 Mazdutide 6.0 mg = 61 Placebo = 62 |
24 weeks | Chinese 18–75-year-old adults with overweight (BMI ≥ 24 kg/m2) with hyperphagia and/or at least one weight-related comorbidity or with obesity (BMI ≥ 28 kg/m2), without diabetes | Mazdutide 3.0 mg = −6.7% Mazdutide 4.5 mg = −10.4% Mazdutide 6.0 mg = −11.3% Placebo = −1.0% |
Bodyweight reduction threshold at week 24 (≥5%; ≥10%; ≥15%): Mazdutide 3.0 mg = 58%; 19%; 10% Mazdutide 4.5 mg = 82%; 49%; 16% Mazdutide 6.0 mg = 80%; 51%; 26% Placebo = 5%; 0%; 0% |
| Véniant et al.52 | Total = 26 MariTide 140 mg = 6 MariTide 280 mg = 6 MariTide 420 mg = 8 Placebo = 6 |
12 weeks (3 doses -monthly injection) | 18–65-year-old adults with a BMI between 30 and 40 kg/m2, without diabetes | MariTide 140 mg = −7.2% MariTide 280 mg = −9.9% MariTide 420 mg = −14.5% Placebo = −1.5% |
– |
| Triple (GLP-1/GIP/glucagon) RA | |||||
| Retatrutide Phase 2 Obesitya53 | Total = 338 Retatrutide 1 mg = 69 Retatrutide 4 mg (ID 2 mg) = 33 Retatrutide 4 mg (ID 4 mg) = 34 Retatrutide 8 mg (ID 2 mg) = 35 Retatrutide 8 mg (ID 4 mg) = 35 Retatrutide 12 mg (ID 2 mg) = 62 Placebo = 70 |
48 weeks | 18–75-year-old adults with at least one unsuccessful weight loss attempt, a BMI between 30 and 50 kg/m2 or ≥ 27 kg/m2 with at least one weight-related condition, without diabetes | At week 24: Retatrutide 1 mg = −7.2% Retatrutide 4 mg (ID 2 mg) = −11.8% Retatrutide 4 mg (ID 4 mg) = −13.9% Retatrutide 8 mg (ID 2 mg) = −16.7% Retatrutide 8 mg (ID 4 mg) = −17.9% Retatrutide 12 mg (ID 2 mg) = −17.5% Placebo = −1.6% At week 48: Retatrutide 1 mg = −8.7% Retatrutide 4 mg (ID 2 mg) = −16.3% Retatrutide 4 mg (ID 4 mg) = −17.8% Retatrutide 8 mg (ID 2 mg) = −21.7% Retatrutide 8 mg (ID 4 mg) = −23.9% Retatrutide 12 mg (ID 2 mg) = −24.2% Placebo = 2.1% |
Bodyweight reduction threshold at week 48 (≥5%; ≥10%; ≥15%; ≥20%; ≥25%; 30%): Retatrutide 1 mg = 64%; 27%; 16%; 6%; 6%; 1% Retatrutide 4 mg (ID 2 mg) = 87%; 73%; 55%; 31; 14%; 6% Retatrutide 4 mg (ID 4 mg) = 91%; 76%; 64%; 29%; 19%; 10% Retatrutide 8 mg (ID 2 mg) = 100%; 90%; 73%; 50%; 36%; 16% Retatrutide 8 mg (ID 4 mg) = 100%; 91%; 77%; 70%; 43%; 17% Retatrutide 12 mg (ID 2 mg) = 100%; 93%; 83%; 63%; 48%; 26% Placebo = 27%; 9%; 2%; 1%; 0%; 0% |
GLP-1, glucagon-like peptide-1; GIP, glucose-dependent insulinotropic polypeptide; RA, receptor agonist; MTD, maximum tolerated dose (10-mg or 15-mg); ILI, intensive lifestyle intervention; IBT, intensive behavioral therapy; ID, initial dose.
a
Adjunct to lifestyle/behavioral intervention in all groups, with counseling, and diet and exercise recommendations.
b
Intensive behavioral therapy + Liraglutide 3.0 mg + 12 weeks of 1000–1200 kcal diet (from week 4 to week 16).