Weight loss of 15 percent or more
Overweight or obesity without diabetes (adults)
In plain language
Across 11 trials with 3,569 participants, 10 of 13 treatments had a clearly better result than placebo on weight loss of 15 percent or more, and for 3 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide and bimagrumab 2.4 to 30 mg injection once weekly: odds ratio 40.91 (95% credible interval 13.54 to 124).
Higher values favor the treatment. "Clearly" means the 95% credible interval excludes no difference. These are averages across trials; they do not say how any one person will respond. Not medical advice.
Network of trials
Effects compared with Placebo
| Treatment | Bayesian OR (95% CrI) | 95% prediction interval | Frequentist OR (95% CI) | Verdict |
|---|---|---|---|---|
| Semaglutide and bimagrumab 2.4 to 30 mg injection once weekly BIMASEMA_SC_2p4-30MG_QW | 40.91 (13.54 to 124) | 10.10 to 151 | 59.17 (19.07 to 184) | Better |
| Semaglutide 50 mg oral once daily (higher dose oral program) SEMA_PO_50MG_QD | 18.00 (6.83 to 41.71) | 5.27 to 52.83 | 18.91 (8.17 to 43.77) | Better |
| Semaglutide and bimagrumab 1.0 to 30 mg injection once weekly BIMASEMA_SC_1p0-30MG_QW | 17.23 (5.84 to 48.24) | 4.76 to 59.26 | 23.95 (8.33 to 68.87) | Better |
| Semaglutide and bimagrumab 2.4 to 10 mg injection once weekly BIMASEMA_SC_2p4-10MG_QW | 13.68 (4.65 to 37.85) | 3.57 to 45.41 | 19.14 (6.61 to 55.41) | Better |
| Semaglutide 2.4 mg subcutaneous once weekly SEMA_SC_2p4MG_QW | 13.02 (8.93 to 20.10) | 5.75 to 32.84 | 13.76 (9.02 to 20.97) | Better |
| Semaglutide and bimagrumab 1.0 to 10 mg injection once weekly BIMASEMA_SC_1p0-10MG_QW | 7.97 (2.66 to 21.42) | 2.09 to 26.70 | 11.09 (3.84 to 32.08) | Better |
| Tirzepatide 15 mg subcutaneous once weekly TIRZ_SC_15MG_QW | 7.91 (1.86 to 37.51) | 1.59 to 42.80 | 9.83 (1.85 to 52.17) | Better |
| Semaglutide 1.7 mg injection once weekly SEMA_SC_1p7MG_QW | 6.33 (2.62 to 15.95) | 2.03 to 20.74 | 6.96 (2.86 to 16.92) | Better |
| Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW | 6.18 (2.10 to 16.75) | 1.53 to 20.15 | 8.64 (3.01 to 24.83) | Better |
| Bimagrumab OTHER_ACTIVE_bimagrumab | 3.80 (1.33 to 10.00) | 1.04 to 12.33 | 5.22 (1.88 to 14.50) | Better |
| Tirzepatide 10 mg subcutaneous once weekly TIRZ_SC_10MG_QW | 2.89 (0.67 to 14.78) | 0.56 to 16.56 | 3.70 (0.66 to 20.63) | Unclear |
| Liraglutide 3.0 mg subcutaneous once daily LIRA_SC_3p0MG_QD | 1.52 (0.62 to 3.75) | 0.47 to 5.02 | 1.60 (0.63 to 4.09) | Unclear |
| Standard care or no added treatment STANDARD_CARE | 0.30 (0.08 to 1.24) | 0.06 to 1.49 | 0.33 (0.08 to 1.38) | Unclear |
Ranking
League table
| Row versus column | PLACEBO | BIMASEMA_SC_2p4-30MG_QW | SEMA_PO_50MG_QD | BIMASEMA_SC_1p0-30MG_QW | BIMASEMA_SC_2p4-10MG_QW | SEMA_SC_2p4MG_QW | BIMASEMA_SC_1p0-10MG_QW | TIRZ_SC_15MG_QW | SEMA_SC_1p7MG_QW | SEMA_SC_1p0MG_QW | OTHER_ACTIVE_bimagrumab | TIRZ_SC_10MG_QW | LIRA_SC_3p0MG_QD | STANDARD_CARE |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 0.02 0.01 to 0.07 | 0.06 0.02 to 0.15 | 0.06 0.02 to 0.17 | 0.07 0.03 to 0.22 | 0.08 0.05 to 0.11 | 0.13 0.05 to 0.38 | 0.13 0.03 to 0.54 | 0.16 0.06 to 0.38 | 0.16 0.06 to 0.48 | 0.26 0.10 to 0.75 | 0.35 0.07 to 1.49 | 0.66 0.27 to 1.62 | 3.30 0.81 to 12.97 |
| BIMASEMA_SC_2p4-30MG_QW | 40.91 13.54 to 124 | BIMASEMA_SC_2p4-30MG_QW | 2.30 0.55 to 9.68 | 2.42 0.73 to 7.95 | 3.04 0.95 to 10.05 | 3.13 1.03 to 9.08 | 5.23 1.60 to 17.48 | 5.21 0.73 to 31.49 | 6.62 1.57 to 24.09 | 6.71 2.11 to 21.82 | 10.96 3.53 to 33.72 | 14.00 1.92 to 88.20 | 27.50 6.39 to 101 | 137 22.82 to 712 |
| SEMA_PO_50MG_QD | 18.00 6.83 to 41.71 | 0.43 0.10 to 1.80 | SEMA_PO_50MG_QD | 1.04 0.26 to 4.03 | 1.31 0.35 to 5.10 | 1.39 0.45 to 3.49 | 2.24 0.58 to 9.17 | 2.26 0.37 to 11.61 | 2.83 0.69 to 9.60 | 2.92 0.73 to 11.18 | 4.70 1.21 to 18.18 | 6.13 0.94 to 33.57 | 11.95 2.99 to 39.43 | 59.95 10.24 to 280 |
| BIMASEMA_SC_1p0-30MG_QW | 17.23 5.84 to 48.24 | 0.41 0.13 to 1.36 | 0.96 0.25 to 3.79 | BIMASEMA_SC_1p0-30MG_QW | 1.26 0.41 to 3.90 | 1.32 0.45 to 3.50 | 2.16 0.70 to 6.86 | 2.19 0.33 to 12.63 | 2.75 0.67 to 9.15 | 2.78 0.92 to 8.54 | 4.51 1.54 to 13.50 | 5.87 0.85 to 36.25 | 11.31 2.78 to 41.89 | 56.16 9.31 to 306 |
| BIMASEMA_SC_2p4-10MG_QW | 13.68 4.65 to 37.85 | 0.33 0.10 to 1.05 | 0.76 0.20 to 2.89 | 0.79 0.26 to 2.45 | BIMASEMA_SC_2p4-10MG_QW | 1.05 0.35 to 2.68 | 1.72 0.55 to 5.33 | 1.72 0.25 to 9.96 | 2.16 0.55 to 7.50 | 2.21 0.72 to 6.84 | 3.61 1.21 to 10.48 | 4.69 0.65 to 28.67 | 9.05 2.17 to 31.63 | 45.20 7.47 to 227 |
| SEMA_SC_2p4MG_QW | 13.02 8.93 to 20.10 | 0.32 0.11 to 0.97 | 0.72 0.29 to 2.20 | 0.76 0.29 to 2.23 | 0.95 0.37 to 2.87 | SEMA_SC_2p4MG_QW | 1.64 0.63 to 4.96 | 1.66 0.34 to 7.34 | 2.06 0.89 to 4.85 | 2.11 0.82 to 6.15 | 3.42 1.39 to 9.76 | 4.54 0.85 to 21.20 | 8.59 3.60 to 20.97 | 42.90 11.14 to 167 |
| BIMASEMA_SC_1p0-10MG_QW | 7.97 2.66 to 21.42 | 0.19 0.06 to 0.63 | 0.45 0.11 to 1.71 | 0.46 0.15 to 1.43 | 0.58 0.19 to 1.83 | 0.61 0.20 to 1.59 | BIMASEMA_SC_1p0-10MG_QW | 0.99 0.15 to 5.63 | 1.26 0.31 to 4.29 | 1.28 0.43 to 3.92 | 2.09 0.70 to 6.08 | 2.69 0.38 to 16.47 | 5.24 1.25 to 18.68 | 26.14 4.52 to 137 |
| TIRZ_SC_15MG_QW | 7.91 1.86 to 37.51 | 0.19 0.03 to 1.36 | 0.44 0.09 to 2.72 | 0.46 0.08 to 3.04 | 0.58 0.10 to 3.96 | 0.60 0.14 to 2.92 | 1.01 0.18 to 6.82 | TIRZ_SC_15MG_QW | 1.24 0.22 to 7.78 | 1.29 0.22 to 8.41 | 2.08 0.39 to 12.84 | 2.70 0.82 to 8.99 | 5.21 0.93 to 31.61 | 26.34 3.31 to 208 |
| SEMA_SC_1p7MG_QW | 6.33 2.62 to 15.95 | 0.15 0.04 to 0.64 | 0.35 0.10 to 1.45 | 0.36 0.11 to 1.49 | 0.46 0.13 to 1.83 | 0.48 0.21 to 1.13 | 0.79 0.23 to 3.22 | 0.81 0.13 to 4.50 | SEMA_SC_1p7MG_QW | 1.02 0.29 to 4.00 | 1.66 0.51 to 6.60 | 2.20 0.34 to 12.50 | 4.15 1.29 to 14.06 | 20.51 4.17 to 103 |
| SEMA_SC_1p0MG_QW | 6.18 2.10 to 16.75 | 0.15 0.05 to 0.47 | 0.34 0.09 to 1.36 | 0.36 0.12 to 1.09 | 0.45 0.15 to 1.39 | 0.47 0.16 to 1.22 | 0.78 0.26 to 2.35 | 0.78 0.12 to 4.45 | 0.98 0.25 to 3.40 | SEMA_SC_1p0MG_QW | 1.63 0.55 to 4.79 | 2.09 0.31 to 13.00 | 4.06 1.04 to 14.39 | 20.28 3.55 to 105 |
| OTHER_ACTIVE_bimagrumab | 3.80 1.33 to 10.00 | 0.09 0.03 to 0.28 | 0.21 0.05 to 0.82 | 0.22 0.07 to 0.65 | 0.28 0.10 to 0.83 | 0.29 0.10 to 0.72 | 0.48 0.16 to 1.42 | 0.48 0.08 to 2.55 | 0.60 0.15 to 1.96 | 0.62 0.21 to 1.83 | OTHER_ACTIVE_bimagrumab | 1.30 0.19 to 7.33 | 2.53 0.67 to 8.63 | 12.54 2.31 to 63.04 |
| TIRZ_SC_10MG_QW | 2.89 0.67 to 14.78 | 0.07 0.01 to 0.52 | 0.16 0.03 to 1.07 | 0.17 0.03 to 1.18 | 0.21 0.03 to 1.55 | 0.22 0.05 to 1.17 | 0.37 0.06 to 2.61 | 0.37 0.11 to 1.22 | 0.45 0.08 to 2.92 | 0.48 0.08 to 3.25 | 0.77 0.14 to 5.27 | TIRZ_SC_10MG_QW | 1.93 0.33 to 12.17 | 9.70 1.24 to 76.30 |
| LIRA_SC_3p0MG_QD | 1.52 0.62 to 3.75 | 0.04 0.01 to 0.16 | 0.08 0.03 to 0.33 | 0.09 0.02 to 0.36 | 0.11 0.03 to 0.46 | 0.12 0.05 to 0.28 | 0.19 0.05 to 0.80 | 0.19 0.03 to 1.08 | 0.24 0.07 to 0.78 | 0.25 0.07 to 0.96 | 0.40 0.12 to 1.49 | 0.52 0.08 to 3.05 | LIRA_SC_3p0MG_QD | 4.93 1.71 to 15.54 |
| STANDARD_CARE | 0.30 0.08 to 1.24 | 0.01 0.00 to 0.04 | 0.02 0.00 to 0.10 | 0.02 0.00 to 0.11 | 0.02 0.00 to 0.13 | 0.02 0.01 to 0.09 | 0.04 0.01 to 0.22 | 0.04 0.00 to 0.30 | 0.05 0.01 to 0.24 | 0.05 0.01 to 0.28 | 0.08 0.02 to 0.43 | 0.10 0.01 to 0.81 | 0.20 0.06 to 0.59 | STANDARD_CARE |
Heterogeneity, fit and convergence
Bayesian random effects (primary)
Frequentist check (netmeta)
Inconsistency
No comparison here has both direct and indirect evidence, so inconsistency cannot be checked by node splitting; the between designs Q above is the global check.
Small study effects
Fewer than ten trial comparisons, too few to judge funnel plot asymmetry.
Baseline characteristics of the trials
| Trial | Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 6 of 11 | Type 2 diabetes share in weight trials (percent of participants) effect modifier; 11 of 11 | Sex (percent female) effect modifier, prognostic factor; 11 of 11 | Treatment duration (weeks) effect modifier; 11 of 11 | Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 11 of 11 |
|---|---|---|---|---|---|
| STEP 5 S000214 | 38.55 | 0 population codes | 77.6 | 104 | standard |
| BARI-STEP S000434 | 41.5 | 10 | 82.85 | 68 | standard |
| NCT05616013 S000715 | 37.3 | 0 population codes | 57.37 | 48 | standard |
| STEP 10 S000832 | 39.9 | 0 population codes | 71.01 | 52 | not_reported |
| STEP 3 S000988 | 38 | 0 population codes | 81.01 | 68 | intensive |
| SURMOUNT-CN S001086 | body weight 91.8 kg | 0 population codes | 49.05 | 52 | standard |
| STEP7 S001288 | not reported | 0 population codes | 45.33 | 44 | standard |
| OASIS 1 S001472 | not reported | 0 population codes | 72.71 | 68 | not_reported |
| STEP 8 S001600 | not reported | 0 population codes | 78.4 | 68 | standard |
| STRIVE S001687 | 45.96 | 35.5 | 64.28 | 104 | intensive |
| STEP 6 S002102 | not reported | 0 population codes | 36.91 | 68 | not_reported |
Comparability of the trials
- FlagBaseline, Baseline BMI or body weight: not reported by 5 of 11 trials
- FlagBaseline, Baseline BMI or body weight: design means range from 37.3 (BIMASEMA_SC_1p0-10MG_QW vs BIMASEMA_SC_1p0-30MG_QW vs BIMASEMA_SC_2p4-10MG_QW vs BIMASEMA_SC_2p4-30MG_QW vs OTHER_ACTIVE_bimagrumab vs PLACEBO vs SEMA_SC_1p0MG_QW vs SEMA_SC_2p4MG_QW) to 46.0 (LIRA_SC_3p0MG_QD vs STANDARD_CARE) kg/m2; threshold 3
- FlagBaseline, Type 2 diabetes share in weight trials: design means range from 0.0 (BIMASEMA_SC_1p0-10MG_QW vs BIMASEMA_SC_1p0-30MG_QW vs BIMASEMA_SC_2p4-10MG_QW vs BIMASEMA_SC_2p4-30MG_QW vs OTHER_ACTIVE_bimagrumab vs PLACEBO vs SEMA_SC_1p0MG_QW vs SEMA_SC_2p4MG_QW) to 35.5 (LIRA_SC_3p0MG_QD vs STANDARD_CARE) percent of participants; threshold 20
- FlagBaseline, Sex: design means range from 36.9 (PLACEBO vs SEMA_SC_1p7MG_QW vs SEMA_SC_2p4MG_QW) to 78.4 (LIRA_SC_3p0MG_QD vs PLACEBO vs SEMA_SC_2p4MG_QW) percent female; threshold 15
- FlagBaseline, Treatment duration: design means range from 48.0 (BIMASEMA_SC_1p0-10MG_QW vs BIMASEMA_SC_1p0-30MG_QW vs BIMASEMA_SC_2p4-10MG_QW vs BIMASEMA_SC_2p4-30MG_QW vs OTHER_ACTIVE_bimagrumab vs PLACEBO vs SEMA_SC_1p0MG_QW vs SEMA_SC_2p4MG_QW) to 104.0 (LIRA_SC_3p0MG_QD vs STANDARD_CARE) weeks; threshold 26
- NoteOutcome assessment, time point: selected time points span 44 to 78 weeks
- NoteOutcome assessment, analysis set: mixed: completers 3, full_analysis 7, modified_itt 1
- NoteOutcome assessment, proportion method: mixed: not stated 9, observed 2
- NoteRisk of bias, blinding: mixed: double_blind 9, open_label 2
- NoteRisk of bias, funding: mixed: industry 10, mixed 1
- NoteData handling, input conversions: arms_combined 1, count_from_percent 11
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| STEP 5 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2018 | age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c below 6.5 percent |
| BARI-STEP | 68 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | mixed | 2022 | age 18 to 65; at least 1 year after primary bypass or sleeve; less than 20 percent weight loss from surgery |
| NCT05616013 | 48 | completers | not stated | not stated | not stated | observed | not stated | not stated | open_label | industry | 2022 | adults 18 to 80; BMI 30 or more, or 27 or more with comorbidity; no diabetes (HbA1c below 6.5 percent); weight below 150 kg |
| STEP 10 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | Adults with obesity and prediabetes; diabetes excluded |
| STEP 3 | 68 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2018 | BMI 30 or more, or 27 with comorbidity; no type 2 diabetes |
| SURMOUNT-CN | 78 | completers | not stated | not stated | not stated | observed | not stated | not stated | double_blind | industry | 2021 | Chinese adults; BMI 28 or more, or 24 or more with a weight related comorbidity; no diabetes |
| STEP7 | 44 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2020 | age 18 or older; BMI 30 or more, or 27 or more with a weight related comorbidity including T2D |
| OASIS 1 | 68 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | overweight or obesity |
| STEP 8 | 68 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2019 | age 18 or older; BMI 30 or higher, or 27 with a weight related comorbidity; no type 2 diabetes |
| STRIVE | 52 | completers | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2017 | age 18 to 75; BMI 35 or more plus prediabetes, T2D, hypertension or sleep apnea; no insulin or GLP-1 RA |
| STEP 6 | 68 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2019 |
Trial data
| Trial | Arm | Treatment | Week | Data | Value | SE | Events / N | Flags | Source |
|---|---|---|---|---|---|---|---|---|---|
| STEP 5 | A1 | SEMA_SC_2p4MG_QW | 52 | arm, responders | 78 / 149 | registry:outcomes | |||
| STEP 5 | A2 | PLACEBO | 52 | arm, responders | 7 / 129 | registry:outcomes | |||
| BARI-STEP | A1 | PLACEBO | 68 | arm, responders | 2 / 29 | R0014003:Results | |||
| BARI-STEP | A2 | SEMA_SC_2p4MG_QW | 68 | arm, responders | 21 / 34 | R0014003:Results | |||
| NCT05616013 | A1 | PLACEBO | 48 | arm, responders | 2 / 35 | count_from_percent | registry:outcomes | ||
| NCT05616013 | A2+A3 | OTHER_ACTIVE_bimagrumab | 48 | arm, responders | 17 / 68 | count_from_percent;arms_combined | registry:outcomes | ||
| NCT05616013 | A4 | SEMA_SC_1p0MG_QW | 48 | arm, responders | 16 / 45 | count_from_percent | registry:outcomes | ||
| NCT05616013 | A5 | SEMA_SC_2p4MG_QW | 48 | arm, responders | 24 / 51 | count_from_percent | registry:outcomes | ||
| NCT05616013 | A6 | BIMASEMA_SC_1p0-10MG_QW | 48 | arm, responders | 17 / 41 | count_from_percent | registry:outcomes | ||
| NCT05616013 | A7 | BIMASEMA_SC_2p4-10MG_QW | 48 | arm, responders | 22 / 40 | count_from_percent | registry:outcomes | ||
| NCT05616013 | A8 | BIMASEMA_SC_1p0-30MG_QW | 48 | arm, responders | 26 / 43 | count_from_percent | registry:outcomes | ||
| NCT05616013 | A9 | BIMASEMA_SC_2p4-30MG_QW | 48 | arm, responders | 34 / 43 | count_from_percent | registry:outcomes | ||
| STEP 10 | A1 | SEMA_SC_2p4MG_QW | 52 | arm, responders | 62 / 129 | registry:outcomes | |||
| STEP 10 | A2 | PLACEBO | 52 | arm, responders | 1 / 66 | registry:outcomes | |||
| STEP 3 | A1 | SEMA_SC_2p4MG_QW | 68 | arm, responders | 208 / 373 | registry:outcomes | |||
| STEP 3 | A2 | PLACEBO | 68 | arm, responders | 25 / 189 | registry:outcomes | |||
| SURMOUNT-CN | A1 | TIRZ_SC_10MG_QW | 78 | arm, responders | 9 / 54 | count_from_percent | R0007857:Results | ||
| SURMOUNT-CN | A2 | TIRZ_SC_15MG_QW | 78 | arm, responders | 17 / 49 | count_from_percent | R0007857:Results | ||
| SURMOUNT-CN | A3 | PLACEBO | 78 | arm, responders | 2 / 39 | count_from_percent | R0007857:Results | ||
| STEP7 | A1 | SEMA_SC_2p4MG_QW | 44 | arm, responders | 82 / 238 | registry:outcomes | |||
| STEP7 | A2 | PLACEBO | 44 | arm, responders | 7 / 116 | registry:outcomes | |||
| OASIS 1 | A1 | SEMA_PO_50MG_QD | 68 | arm, responders | 170 / 317 | registry:outcomes | |||
| OASIS 1 | A2 | PLACEBO | 68 | arm, responders | 17 / 295 | registry:outcomes | |||
| STEP 8 | A1 | SEMA_SC_2p4MG_QW | 68 | arm, responders | 65 / 117 | registry:outcomes | |||
| STEP 8 | A2 | LIRA_SC_3p0MG_QD | 68 | arm, responders | 14 / 117 | registry:outcomes | |||
| STEP 8 | A3 | PLACEBO | 68 | arm, responders | 5 / 78 | registry:outcomes | |||
| STRIVE | A1 | STANDARD_CARE | 52 | arm, responders | 6 / 93 | R0020855:Table 2 | |||
| STRIVE | A2 | LIRA_SC_3p0MG_QD | 52 | arm, responders | 51 / 201 | R0020855:Table 2 | |||
| STEP 6 | A1 | SEMA_SC_1p7MG_QW | 68 | arm, responders | 24 / 98 | registry:outcomes | |||
| STEP 6 | A2 | SEMA_SC_2p4MG_QW | 68 | arm, responders | 79 / 193 | registry:outcomes | |||
| STEP 6 | A3 | PLACEBO | 68 | arm, responders | 3 / 100 | registry:outcomes |
Rerun this analysis yourself
Remove treatments or trials and refit the frequentist and Bayesian models in your browser, with the same methods as the published analysis.