Network meta-analysis
Percent body weight change
Overweight or obesity without diabetes (adults)
weeks 20 to 40 (target week 26)Not stated by the trialsDoses of a drug pooledMean difference
13
Randomized trials
10
Treatments
2,153
Participants
26
Trial arms
In plain language
Across 13 trials with 2,153 participants, 5 of 9 treatments had a clearly better result than placebo on percent body weight change, and for 4 the evidence could not tell them apart from placebo. The most favorable estimate was for Bofanglutide (GZR18) injection: mean difference -12.54 percentage points (95% credible interval -20.09 to -4.09).
Lower 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
Each circle is a treatment; each line joins treatments that were randomized against each other in at least one trial.
Effects compared with Placebo
Mean difference in percentage points. Lower values favor the treatment.
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Bofanglutide (GZR18) injection BOFANG_SC | -12.54 (-20.09 to -4.09) | -23.54 to -1.08 | -13.12 (-20.52 to -5.71) | Better |
| Mazdutide injection MAZD_SC | -12.29 (-17.93 to -6.47) | -22.03 to -2.53 | -12.67 (-18.09 to -7.26) | Better |
| Orforglipron tablet ORFO_PO | -9.03 (-16.72 to -0.84) | -20.00 to 2.26 | -9.33 (-16.72 to -1.94) | Better |
| Semaglutide injection SEMA_SC | -8.66 (-14.55 to -2.75) | -18.63 to 1.49 | -9.01 (-14.49 to -3.52) | Better |
| Efpe sc EFPE_SC | -6.81 (-14.60 to 0.97) | -18.14 to 4.47 | -7.13 (-14.42 to 0.16) | Unclear |
| Liraglutide injection LIRA_SC | -5.16 (-9.81 to -0.42) | -14.66 to 4.03 | -5.22 (-9.50 to -0.94) | Better |
| Exenatide extended release injection EXENER_SC | -3.94 (-11.82 to 4.09) | -14.96 to 7.15 | -4.20 (-11.72 to 3.32) | Unclear |
| Exenatide injection EXEN_SC | -3.18 (-10.98 to 4.32) | -14.56 to 7.54 | -3.30 (-10.54 to 3.94) | Unclear |
| Standard care or no added treatment STANDARD_CARE | -0.79 (-9.49 to 8.42) | -12.62 to 11.23 | -0.80 (-9.28 to 7.68) | Unclear |
Ranking
How likely each treatment is to be among the best. Rankings ignore the size of differences and their certainty, so read them with the effects above.
League table
Every treatment against every other: mean difference of the row treatment versus the column treatment, posterior median and 95% credible interval. Green: row clearly better; red: row clearly worse.
| Row versus column | PLACEBO | BOFANG_SC | MAZD_SC | ORFO_PO | SEMA_SC | EFPE_SC | LIRA_SC | EXENER_SC | EXEN_SC | STANDARD_CARE |
|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 12.54 4.09 to 20.09 | 12.29 6.47 to 17.93 | 9.03 0.84 to 16.72 | 8.66 2.75 to 14.55 | 6.81 -0.97 to 14.60 | 5.16 0.42 to 9.81 | 3.94 -4.09 to 11.82 | 3.18 -4.32 to 10.98 | 0.79 -8.42 to 9.49 |
| BOFANG_SC | -12.54 -20.09 to -4.09 | BOFANG_SC | -0.25 -9.64 to 9.84 | -3.49 -14.54 to 7.63 | -3.95 -13.21 to 6.41 | -5.73 -16.38 to 5.88 | -7.38 -16.23 to 2.50 | -8.63 -19.53 to 3.22 | -9.40 -19.78 to 2.56 | -11.77 -23.50 to 1.04 |
| MAZD_SC | -12.29 -17.93 to -6.47 | 0.25 -9.84 to 9.64 | MAZD_SC | -3.24 -13.16 to 6.38 | -3.66 -11.53 to 4.84 | -5.42 -15.21 to 4.41 | -7.17 -14.49 to 0.68 | -8.34 -18.19 to 1.38 | -9.08 -18.56 to 0.24 | -11.48 -21.95 to -0.66 |
| ORFO_PO | -9.03 -16.72 to -0.84 | 3.49 -7.63 to 14.54 | 3.24 -6.38 to 13.16 | ORFO_PO | -0.41 -9.96 to 9.89 | -2.17 -13.16 to 8.88 | -3.84 -12.83 to 5.50 | -5.06 -16.18 to 6.10 | -5.90 -16.55 to 5.60 | -8.23 -20.17 to 3.55 |
| SEMA_SC | -8.66 -14.55 to -2.75 | 3.95 -6.41 to 13.21 | 3.66 -4.84 to 11.53 | 0.41 -9.89 to 9.96 | SEMA_SC | -1.80 -11.47 to 7.64 | -3.44 -11.19 to 3.97 | -4.67 -14.42 to 4.94 | -5.48 -14.90 to 4.27 | -7.88 -18.69 to 2.68 |
| EFPE_SC | -6.81 -14.60 to 0.97 | 5.73 -5.88 to 16.38 | 5.42 -4.41 to 15.21 | 2.17 -8.88 to 13.16 | 1.80 -7.64 to 11.47 | EFPE_SC | -1.67 -10.69 to 7.66 | -2.81 -14.19 to 8.23 | -3.60 -14.60 to 7.48 | -6.03 -18.11 to 5.90 |
| LIRA_SC | -5.16 -9.81 to -0.42 | 7.38 -2.50 to 16.23 | 7.17 -0.68 to 14.49 | 3.84 -5.50 to 12.83 | 3.44 -3.97 to 11.19 | 1.67 -7.66 to 10.69 | LIRA_SC | -1.19 -10.47 to 7.95 | -1.95 -11.03 to 7.15 | -4.43 -12.10 to 3.41 |
| EXENER_SC | -3.94 -11.82 to 4.09 | 8.63 -3.22 to 19.53 | 8.34 -1.38 to 18.19 | 5.06 -6.10 to 16.18 | 4.67 -4.94 to 14.42 | 2.81 -8.23 to 14.19 | 1.19 -7.95 to 10.47 | EXENER_SC | -0.84 -11.78 to 10.31 | -3.19 -15.33 to 8.80 |
| EXEN_SC | -3.18 -10.98 to 4.32 | 9.40 -2.56 to 19.78 | 9.08 -0.24 to 18.56 | 5.90 -5.60 to 16.55 | 5.48 -4.27 to 14.90 | 3.60 -7.48 to 14.60 | 1.95 -7.15 to 11.03 | 0.84 -10.31 to 11.78 | EXEN_SC | -2.36 -14.27 to 9.08 |
| STANDARD_CARE | -0.79 -9.49 to 8.42 | 11.77 -1.04 to 23.50 | 11.48 0.66 to 21.95 | 8.23 -3.55 to 20.17 | 7.88 -2.68 to 18.69 | 6.03 -5.90 to 18.11 | 4.43 -3.41 to 12.10 | 3.19 -8.80 to 15.33 | 2.36 -9.08 to 14.27 | STANDARD_CARE |
Heterogeneity, fit and convergence
Bayesian random effects (primary)
Frequentist check (netmeta)
Inconsistency
Do trials comparing two treatments directly agree with the indirect evidence through other treatments?
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
A comparison adjusted funnel plot: each point is one trial comparison, centered on its own network estimate. Asymmetry can signal that small trials with unfavorable results are missing.
Fewer than ten trial comparisons, too few to judge funnel plot asymmetry.
Baseline characteristics of the trials
The baseline value of each effect modifier or prognostic factor that applies here, per trial: mean or percent over arms, weighted by the number randomized. A note under a value names a stand in (a median for a mean, 100 minus the male share, Asian subgroup rows, an all Asian site list); "not reported" means no source of the trial prints it.
| Trial | Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 13 of 13 | Type 2 diabetes share in weight trials (percent of participants) effect modifier; 13 of 13 | Sex (percent female) effect modifier, prognostic factor; 13 of 13 | Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 9 of 13 | Treatment duration (weeks) effect modifier; 13 of 13 | Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 13 of 13 |
|---|---|---|---|---|---|---|
| BARI-STEP S000434 | 41.5 | 10 | 82.85 | 2.85 | 68 | standard |
| BARIOPTIMISE S000466 | 43.1 | 13 | 74 | 7.14 | 24 | standard |
| NCT00500370 S000663 | 39.51 | 0 population codes | 76.69 | not reported | 24 | intensive |
| NCT02075281 S000743 | 35.44 | 0 population codes | 76.35 | 8.49 | 20 | standard |
| NCT04904913 S001183 | 31.83 | 0 population codes | 52.03 | 100 | 24 | none |
| Dapalost S001235 | 35.4 | 0 population codes | 61.25 | not reported | 24 | standard |
| STABLE Wt Loss S001294 | 37.48 | 0 population codes | 78.36 | 4.2 | 60 | not_reported;standard |
| NCT05623839 S001559 | 32.5 | 0 population codes | 50 | not reported | 20 | none |
| STRIVE S001687 | 45.96 | 35.5 | 64.28 | 3.56 | 104 | intensive |
| NCT01557166 S002315 | 39.15 | 0 population codes | 28.1 | 4.46 | 32 | standard |
| NCT05051579 S002337 | 38.08 | 0 population codes | 59.19 | 0.74 | 36 | standard |
| NCT06256562 S002790 | 33.23 | 0 population codes | 45.62 | 100 | 30 | standard |
| S003017 S003017 | 38.05 | 0 population codes | 87.5 | not reported | 52.14 | standard |
Comparability of the trials
Checked across designs (the set of treatments each trial compares) for eligibility, outcome definition and assessment, and the baseline factors above. Flags point to possible intransitivity; notes describe variation that is not tied to design.
- FlagBaseline, Baseline BMI or body weight: design means range from 32.2 (MAZD_SC vs PLACEBO) to 46.0 (LIRA_SC vs STANDARD_CARE) kg/m2; threshold 3
- FlagBaseline, Type 2 diabetes share in weight trials: design means range from 0.0 (BOFANG_SC vs PLACEBO) to 35.5 (LIRA_SC vs STANDARD_CARE) percent of participants; threshold 20
- FlagBaseline, Sex: design means range from 45.6 (BOFANG_SC vs PLACEBO) to 80.6 (PLACEBO vs SEMA_SC) percent female; threshold 15
- FlagBaseline, Asian ancestry or region: not reported by 4 of 13 trials
- FlagBaseline, Asian ancestry or region: design means range from 0.7 (ORFO_PO vs PLACEBO) to 100.0 (BOFANG_SC vs PLACEBO) percent Asian; threshold 30
- FlagBaseline, Treatment duration: design means range from 20.0 (EFPE_SC vs PLACEBO) to 104.0 (LIRA_SC vs STANDARD_CARE) weeks; threshold 26
- FlagHeterogeneity, tau above threshold: tau 3.50 exceeds the outcome threshold 2.5; the flags of this network are candidate explanations
- NoteOutcome assessment, time point: selected time points span 20 to 32 weeks
- NoteOutcome assessment, analysis set: mixed: completers 2, full_analysis 3, modified_itt 5, randomized 3
- NoteRisk of bias, blinding: mixed: double_blind 12, open_label 1
- NoteRisk of bias, funding: mixed: industry 11, mixed 2
- NoteData handling, input conversions: arms_combined 5, n_randomized 12
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BARI-STEP | 32 | randomized | 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 |
| BARIOPTIMISE | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | mixed | 2018 | adults at least 1 year after RYGB or sleeve gastrectomy with 20 percent or less weight loss and suboptimal GLP-1 response |
| NCT00500370 | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2007 | adults with BMI 30 or more, without diabetes |
| NCT02075281 | 20 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2014 | age 18 to 64 years; BMI 30 to 42, or 27 to 30 with comorbidity; FPG below 7 mmol/L; HbA1c 6.5 percent or less; no diabetes |
| NCT04904913 | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | Chinese adults 18 to 75; BMI 28 or more, or 24 or more with comorbidity or hyperphagia; no diabetes, HbA1c below 6.5 |
| Dapalost | 24 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2014 | age 18 to 70; BMI 30 to 45 kg/m2; no diabetes |
| STABLE Wt Loss | 20 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2022 | age 18 to 70; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c 6.5 percent or less |
| NCT05623839 | 27 | completers | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2022 | age 18 to 70; BMI 27 to 50; HbA1c below 6.5 percent; no diabetes |
| STRIVE | 32 | 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 |
| NCT01557166 | 32 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2012 | age 18 to 64; BMI 30 or more; AHI 15 or more; no diabetes; unable or unwilling to use CPAP |
| NCT05051579 | 26 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | adults BMI 30 or more, or 27 to 30 with a weight related complication, without diabetes |
| NCT06256562 | 30 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2023 | age 18 to 75; BMI 24 to <28 kg/m2 with comorbidity or 28 or more (Chinese criteria); no diabetes |
| S003017 | 26.07 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2019 | age 20 to 65; BMI above 35; 12 to 36 months after bariatric surgery with suboptimal stable weight loss or regain |
Trial data
What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the mean difference on the analysis scale against the trial's first row. Flags mark converted, combined or approximated inputs.
| Trial | Arm | Treatment | Week | Data | Value | SE | Events / N | Flags | Source |
|---|---|---|---|---|---|---|---|---|---|
| BARI-STEP | A1 | PLACEBO | 32 | arm, percent_change | 0.710 | 1.330 | 30 | R0014003:Supplement Table 6 | |
| BARI-STEP | A2 | SEMA_SC | 32 | arm, percent_change | -12.960 | 1.340 | 34 | R0014003:Supplement Table 6 | |
| BARIOPTIMISE | A1 | PLACEBO | 24 | arm, percent_change | -0.540 | 0.651 | 26 | R0017334:Results | |
| BARIOPTIMISE | A2 | LIRA_SC | 24 | arm, percent_change | -8.820 | 0.887 | 31 | R0017334:Results | |
| NCT00500370 | A1 | EXEN_SC | 24 | contrast, md | -3.300 | 0.500 | R0026955:Results | ||
| NCT00500370 | A2 | PLACEBO | 24 | contrast, md | R0026955:Results | ||||
| NCT02075281 | A1 | PLACEBO | 20 | arm, percent_change | 0.100 | 0.600 | 60 | n_randomized | R0011218:Table 2 |
| NCT02075281 | A2+A3+A4+A5 | EFPE_SC | 20 | arm, percent_change | -7.027 | 0.299 | 237 | n_randomized;arms_combined | R0011218:Table 2 |
| NCT04904913 | A1+A2+A3 | MAZD_SC | 24 | arm, percent_change | -9.462 | 0.428 | 186 | arms_combined | R0016107:Table 2 |
| NCT04904913 | A4 | PLACEBO | 24 | arm, percent_change | 1.000 | 0.700 | 62 | R0016107:Table 2 | |
| Dapalost | A1 | EXENER_SC | 24 | arm, percent_change | -4.470 | 0.804 | 25 | n_randomized | R0025627:Table 2 |
| Dapalost | A2 | PLACEBO | 24 | arm, percent_change | -0.270 | 0.839 | 25 | n_randomized | R0025627:Table 2 |
| STABLE Wt Loss | A1 | SEMA_SC | 20 | arm, percent_change | -9.700 | 0.600 | 72 | n_randomized | R0013679:Table 3 |
| STABLE Wt Loss | A2 | PLACEBO | 20 | arm, percent_change | -4.700 | 0.900 | 48 | n_randomized | R0013679:Table 3 |
| NCT05623839 | A1 | PLACEBO | 27 | arm, percent_change | 1.200 | 1.600 | 6 | R0013210:Results | |
| NCT05623839 | A2+A3 | MAZD_SC | 27 | arm, percent_change | -14.100 | 0.860 | 21 | arms_combined | R0013210:Results |
| STRIVE | A1 | STANDARD_CARE | 32 | arm, percent_change | -4.580 | 0.646 | 79 | registry:outcomes | |
| STRIVE | A2 | LIRA_SC | 32 | arm, percent_change | -9.000 | 0.404 | 208 | registry:outcomes | |
| NCT01557166 | A1 | LIRA_SC | 32 | arm, percent_change | -5.700 | 0.400 | 180 | n_randomized | R0026203:Results |
| NCT01557166 | A2 | PLACEBO | 32 | arm, percent_change | -1.600 | 0.300 | 179 | n_randomized | R0026203:Results |
| NCT05051579 | A1+A2+A3+A5 | ORFO_PO | 26 | arm, percent_change | -11.330 | 0.408 | 208 | arms_combined | registry:outcomes |
| NCT05051579 | A7 | PLACEBO | 26 | arm, percent_change | -2.000 | 0.810 | 48 | registry:outcomes | |
| NCT06256562 | A1+A2+A3+A4+A5 | BOFANG_SC | 30 | arm, percent_change | -14.047 | 0.443 | 274 | n_randomized;arms_combined | R0002409:Supplement Table S2 |
| NCT06256562 | A6 | PLACEBO | 30 | arm, percent_change | -0.930 | 0.830 | 66 | n_randomized | R0002409:Supplement Table S2 |
| S003017 | A1 | LIRA_SC | 26.07 | arm, percent_change | -3.490 | 0.790 | 24 | n_randomized | R0016758:Supplement eTable 1 |
| S003017 | A2 | PLACEBO | 26.07 | arm, percent_change | -0.160 | 0.880 | 24 | n_randomized | R0016758:Supplement eTable 1 |
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.