Network meta-analysis
Percent body weight change
Overweight or obesity without diabetes (adults)
weeks 40 to 104 (target week 68)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean difference
6
Randomized trials
14
Treatments
7,143
Participants
19
Trial arms
In plain language
Across 6 trials with 7,143 participants, 10 of 13 treatments had a clearly better result than placebo on percent body weight change, and for 3 the evidence could not tell them apart from placebo. The most favorable estimate was for Tirzepatide subcutaneous once weekly, maximum tolerated dose: 10 or 15 mg: mean difference -23.57 percentage points (95% credible interval -29.15 to -12.76).
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 |
|---|---|---|---|---|
| Tirzepatide subcutaneous once weekly, maximum tolerated dose: 10 or 15 mg TIRZ_SC_MTD_QW | -23.57 (-29.15 to -12.76) | -32.34 to -9.71 | -24.40 (-26.06 to -22.74) | Better |
| Retatrutide 12 mg subcutaneous once weekly RETA_SC_12MG_QW | -21.07 (-26.96 to -10.14) | -30.13 to -7.27 | -22.11 (-24.93 to -19.29) | Better |
| Retatrutide 8 mg subcutaneous once weekly RETA_SC_8MG_QW | -19.69 (-25.53 to -8.93) | -28.43 to -5.83 | -20.69 (-23.17 to -18.21) | Better |
| Tirzepatide 15 mg subcutaneous once weekly TIRZ_SC_15MG_QW | -19.48 (-24.79 to -9.44) | -28.52 to -5.90 | -20.10 (-21.19 to -19.01) | Better |
| Tirzepatide 10 mg subcutaneous once weekly TIRZ_SC_10MG_QW | -18.37 (-24.06 to -8.12) | -27.29 to -4.57 | -19.00 (-20.09 to -17.91) | Better |
| Semaglutide maximum tolerated dose injection once weekly SEMA_SC_MTD_1p7-2p4_QW | -16.81 (-24.10 to -2.71) | -26.57 to 0.64 | -18.00 (-20.35 to -15.65) | Better |
| Semaglutide 2.4 mg subcutaneous once weekly SEMA_SC_2p4MG_QW | -14.17 (-20.83 to -5.40) | -24.07 to -1.87 | -14.40 (-15.30 to -13.50) | Better |
| Retatrutide 4 mg subcutaneous once weekly RETA_SC_4MG_QW | -13.96 (-20.16 to -3.82) | -22.85 to -0.67 | -14.96 (-17.54 to -12.39) | Better |
| Tirzepatide 5 mg subcutaneous once weekly TIRZ_SC_5MG_QW | -13.04 (-18.53 to -3.14) | -22.19 to 0.27 | -13.60 (-14.69 to -12.51) | Better |
| Orforglipron 36 mg oral once daily ORFO_PO_36MG_QD | -11.21 (-17.31 to -2.31) | -20.79 to 1.08 | -11.48 (-12.34 to -10.62) | Better |
| Orforglipron 12 mg oral once daily ORFO_PO_12MG_QD | -8.14 (-14.54 to 0.90) | -18.46 to 4.05 | -8.40 (-9.22 to -7.58) | Unclear |
| Orforglipron 6 mg oral once daily ORFO_PO_6MG_QD | -6.70 (-13.11 to 2.58) | -16.45 to 5.44 | -6.95 (-7.71 to -6.19) | Unclear |
| Retatrutide 1 mg subcutaneous once weekly RETA_SC_1MG_QW | -5.78 (-11.58 to 4.09) | -15.12 to 7.27 | -6.56 (-8.91 to -4.21) | 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 | TIRZ_SC_MTD_QW | RETA_SC_12MG_QW | RETA_SC_8MG_QW | TIRZ_SC_15MG_QW | TIRZ_SC_10MG_QW | SEMA_SC_MTD_1p7-2p4_QW | SEMA_SC_2p4MG_QW | RETA_SC_4MG_QW | TIRZ_SC_5MG_QW | ORFO_PO_36MG_QD | ORFO_PO_12MG_QD | ORFO_PO_6MG_QD | RETA_SC_1MG_QW |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 23.57 12.76 to 29.15 | 21.07 10.14 to 26.96 | 19.69 8.93 to 25.53 | 19.48 9.44 to 24.79 | 18.37 8.12 to 24.06 | 16.81 2.71 to 24.10 | 14.17 5.40 to 20.83 | 13.96 3.82 to 20.16 | 13.04 3.14 to 18.53 | 11.21 2.31 to 17.31 | 8.14 -0.90 to 14.54 | 6.70 -2.58 to 13.11 | 5.78 -4.09 to 11.58 |
| TIRZ_SC_MTD_QW | -23.57 -29.15 to -12.76 | TIRZ_SC_MTD_QW | -2.35 -13.79 to 8.20 | -3.82 -14.79 to 7.36 | -4.11 -14.44 to 6.60 | -5.28 -15.87 to 6.09 | -6.70 -15.16 to -0.07 | -9.50 -19.01 to 3.01 | -9.48 -20.07 to 1.23 | -10.59 -21.20 to 0.86 | -12.45 -22.10 to -0.51 | -15.54 -24.70 to -3.30 | -16.97 -26.33 to -4.91 | -17.73 -27.69 to -7.02 |
| RETA_SC_12MG_QW | -21.07 -26.96 to -10.14 | 2.35 -8.20 to 13.79 | RETA_SC_12MG_QW | -1.37 -9.34 to 7.40 | -1.73 -12.10 to 9.47 | -2.88 -13.40 to 8.84 | -4.30 -18.03 to 7.49 | -6.98 -16.66 to 5.64 | -7.04 -14.96 to 1.39 | -8.21 -18.58 to 3.33 | -9.96 -19.20 to 1.95 | -13.11 -22.32 to -0.81 | -14.53 -23.89 to -2.36 | -15.29 -22.80 to -6.70 |
| RETA_SC_8MG_QW | -19.69 -25.53 to -8.93 | 3.82 -7.36 to 14.79 | 1.37 -7.40 to 9.34 | RETA_SC_8MG_QW | -0.33 -10.76 to 10.44 | -1.46 -12.11 to 10.17 | -2.91 -16.95 to 8.83 | -5.64 -15.04 to 7.22 | -5.65 -13.67 to 2.80 | -6.76 -17.34 to 5.09 | -8.64 -17.99 to 3.14 | -11.69 -21.25 to 0.40 | -13.15 -22.91 to -0.84 | -13.93 -21.34 to -5.41 |
| TIRZ_SC_15MG_QW | -19.48 -24.79 to -9.44 | 4.11 -6.60 to 14.44 | 1.73 -9.47 to 12.10 | 0.33 -10.44 to 10.76 | TIRZ_SC_15MG_QW | -1.11 -8.97 to 6.73 | -2.58 -16.43 to 8.75 | -5.36 -14.67 to 6.66 | -5.34 -16.03 to 5.33 | -6.42 -13.92 to 1.39 | -8.34 -17.73 to 3.59 | -11.44 -20.93 to 0.51 | -12.85 -22.36 to -0.93 | -13.59 -23.68 to -2.65 |
| TIRZ_SC_10MG_QW | -18.37 -24.06 to -8.12 | 5.28 -6.09 to 15.87 | 2.88 -8.84 to 13.40 | 1.46 -10.17 to 12.11 | 1.11 -6.73 to 8.97 | TIRZ_SC_10MG_QW | -1.44 -15.89 to 9.87 | -4.22 -14.04 to 7.62 | -4.15 -15.30 to 6.86 | -5.36 -13.35 to 3.03 | -7.24 -16.90 to 4.36 | -10.30 -20.13 to 1.61 | -11.77 -21.67 to 0.20 | -12.45 -22.88 to -1.77 |
| SEMA_SC_MTD_1p7-2p4_QW | -16.81 -24.10 to -2.71 | 6.70 0.07 to 15.16 | 4.30 -7.49 to 18.03 | 2.91 -8.83 to 16.95 | 2.58 -8.75 to 16.43 | 1.44 -9.87 to 15.89 | SEMA_SC_MTD_1p7-2p4_QW | -2.80 -13.69 to 12.79 | -2.73 -14.04 to 11.02 | -3.94 -14.78 to 10.37 | -5.76 -16.36 to 9.26 | -8.85 -19.20 to 6.94 | -10.26 -20.58 to 5.11 | -11.00 -22.32 to 3.34 |
| SEMA_SC_2p4MG_QW | -14.17 -20.83 to -5.40 | 9.50 -3.01 to 19.01 | 6.98 -5.64 to 16.66 | 5.64 -7.22 to 15.04 | 5.36 -6.66 to 14.67 | 4.22 -7.62 to 14.04 | 2.80 -12.79 to 13.69 | SEMA_SC_2p4MG_QW | -0.08 -11.94 to 9.70 | -1.12 -12.94 to 9.05 | -2.99 -14.07 to 7.33 | -6.04 -16.78 to 4.46 | -7.47 -18.74 to 3.25 | -8.27 -19.90 to 1.17 |
| RETA_SC_4MG_QW | -13.96 -20.16 to -3.82 | 9.48 -1.23 to 20.07 | 7.04 -1.39 to 14.96 | 5.65 -2.80 to 13.67 | 5.34 -5.33 to 16.03 | 4.15 -6.86 to 15.30 | 2.73 -11.02 to 14.04 | 0.08 -9.70 to 11.94 | RETA_SC_4MG_QW | -1.12 -11.81 to 9.72 | -2.95 -12.66 to 8.48 | -5.98 -15.44 to 5.71 | -7.49 -17.24 to 4.33 | -8.26 -15.93 to -0.00 |
| TIRZ_SC_5MG_QW | -13.04 -18.53 to -3.14 | 10.59 -0.86 to 21.20 | 8.21 -3.33 to 18.58 | 6.76 -5.09 to 17.34 | 6.42 -1.39 to 13.92 | 5.36 -3.03 to 13.35 | 3.94 -10.37 to 14.78 | 1.12 -9.05 to 12.94 | 1.12 -9.72 to 11.81 | TIRZ_SC_5MG_QW | -1.89 -11.72 to 9.59 | -4.95 -14.59 to 6.87 | -6.43 -16.28 to 5.62 | -7.12 -17.75 to 3.73 |
| ORFO_PO_36MG_QD | -11.21 -17.31 to -2.31 | 12.45 0.51 to 22.10 | 9.96 -1.95 to 19.20 | 8.64 -3.14 to 17.99 | 8.34 -3.59 to 17.73 | 7.24 -4.36 to 16.90 | 5.76 -9.26 to 16.36 | 2.99 -7.33 to 14.07 | 2.95 -8.48 to 12.66 | 1.89 -9.59 to 11.72 | ORFO_PO_36MG_QD | -3.08 -10.69 to 5.17 | -4.50 -12.84 to 3.47 | -5.29 -16.57 to 4.32 |
| ORFO_PO_12MG_QD | -8.14 -14.54 to 0.90 | 15.54 3.30 to 24.70 | 13.11 0.81 to 22.32 | 11.69 -0.40 to 21.25 | 11.44 -0.51 to 20.93 | 10.30 -1.61 to 20.13 | 8.85 -6.94 to 19.20 | 6.04 -4.46 to 16.78 | 5.98 -5.71 to 15.44 | 4.95 -6.87 to 14.59 | 3.08 -5.17 to 10.69 | ORFO_PO_12MG_QD | -1.43 -9.74 to 6.39 | -2.26 -13.26 to 7.75 |
| ORFO_PO_6MG_QD | -6.70 -13.11 to 2.58 | 16.97 4.91 to 26.33 | 14.53 2.36 to 23.89 | 13.15 0.84 to 22.91 | 12.85 0.93 to 22.36 | 11.77 -0.20 to 21.67 | 10.26 -5.11 to 20.58 | 7.47 -3.25 to 18.74 | 7.49 -4.33 to 17.24 | 6.43 -5.62 to 16.28 | 4.50 -3.47 to 12.84 | 1.43 -6.39 to 9.74 | ORFO_PO_6MG_QD | -0.79 -12.36 to 9.08 |
| RETA_SC_1MG_QW | -5.78 -11.58 to 4.09 | 17.73 7.02 to 27.69 | 15.29 6.70 to 22.80 | 13.93 5.41 to 21.34 | 13.59 2.65 to 23.68 | 12.45 1.77 to 22.88 | 11.00 -3.34 to 22.32 | 8.27 -1.17 to 19.90 | 8.26 0.00 to 15.93 | 7.12 -3.73 to 17.75 | 5.29 -4.32 to 16.57 | 2.26 -7.75 to 13.26 | 0.79 -9.08 to 12.36 | RETA_SC_1MG_QW |
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; 6 of 6 | Type 2 diabetes share in weight trials (percent of participants) effect modifier; 6 of 6 | Sex (percent female) effect modifier, prognostic factor; 6 of 6 | Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 6 of 6 | Treatment duration (weeks) effect modifier; 6 of 6 | Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 6 of 6 |
|---|---|---|---|---|---|---|
| SURMOUNT-5 S000093 | 39.4 | 0 population codes | 64.65 | 2.4 | 72 | standard |
| STEP 1 S000144 | 37.87 | 0 population codes | 74.07 | 13.33 | 68 | standard |
| SURMOUNT-1 S001077 | 37.94 | 0 population codes | 67.75 | 10.87 | 72 | standard |
| NCT04881760 S001653 | 37.34 | 0 population codes | 48.22 | 1.18 | 48 | standard |
| ATTAIN-1 S001722 | 37 | 0 population codes | 64.25 | 28.27 | 72 | not_reported |
| SURMOUNT-3 S002157 | 35.9 | 0 population codes | 62.9 | 0.7 | 72 | 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 35.9 (PLACEBO vs TIRZ_SC_MTD_QW) to 39.4 (SEMA_SC_MTD_1p7-2p4_QW vs TIRZ_SC_MTD_QW) kg/m2; threshold 3
- FlagBaseline, Sex: design means range from 48.2 (PLACEBO vs RETA_SC_12MG_QW vs RETA_SC_1MG_QW vs RETA_SC_4MG_QW vs RETA_SC_8MG_QW) to 74.1 (PLACEBO vs SEMA_SC_2p4MG_QW) percent female; threshold 15
- FlagHeterogeneity, tau above threshold: tau 2.56 exceeds the outcome threshold 2.5; the flags of this network are candidate explanations
- NoteOutcome assessment, time point: selected time points span 48 to 72 weeks
- NoteOutcome assessment, analysis set: mixed: full_analysis 1, modified_itt 3, other 1, randomized 1
- NoteOutcome assessment, definition: mixed: not stated 5, percent change in body weight from randomization 1
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 1, not stated 5
- NoteRisk of bias, blinding: mixed: double_blind 5, open_label 1
- NoteData handling, input conversions: arms_combined 2
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SURMOUNT-5 | 72 | other | not stated | not stated | not stated | not stated | hypothetical | not stated | open_label | industry | 2023 | adults; BMI 30 or more, or 27 with complication; no diabetes |
| STEP 1 | 68 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2018 | adults; BMI 30 or more, or 27 or more with a weight related condition; no diabetes; HbA1c below 6.5 percent |
| SURMOUNT-1 | 72 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | not stated | double_blind | industry | 2019 | age 18 or older; BMI 30 or more, or 27 or more with a weight related complication; no diabetes |
| NCT04881760 | 48 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | not stated | double_blind | industry | 2021 | 18 to 75 years; BMI 30 or more, or 27 to less than 30 with weight related complication; no type 2 diabetes |
| ATTAIN-1 | 72 | randomized | not stated | not stated | not stated | not stated | hypothetical | not stated | double_blind | industry | 2023 | adults BMI 30 or more, or 27 or more with a weight related complication, without diabetes |
| SURMOUNT-3 | 72 | modified_itt | percent change in body weight from randomization | not stated | not stated | not stated | hypothetical | not stated | double_blind | industry | 2021 | age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; at least 5 percent loss in lead in |
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 |
|---|---|---|---|---|---|---|---|---|---|
| SURMOUNT-5 | A1 | TIRZ_SC_MTD_QW | 72 | arm, percent_change | -21.800 | 0.600 | 367 | registry:outcomes | |
| SURMOUNT-5 | A2 | SEMA_SC_MTD_1p7-2p4_QW | 72 | arm, percent_change | -15.400 | 0.600 | 373 | registry:outcomes | |
| STEP 1 | A1 | SEMA_SC_2p4MG_QW | 68 | contrast, md | -14.400 | 0.459 | R0023399:Results | ||
| STEP 1 | A2 | PLACEBO | 68 | contrast, md | R0023399:Results | ||||
| SURMOUNT-1 | A1 | PLACEBO | 72 | arm, percent_change | -2.400 | 0.400 | 635 | registry:outcomes | |
| SURMOUNT-1 | A2 | TIRZ_SC_5MG_QW | 72 | arm, percent_change | -16.000 | 0.390 | 623 | registry:outcomes | |
| SURMOUNT-1 | A3 | TIRZ_SC_10MG_QW | 72 | arm, percent_change | -21.400 | 0.390 | 629 | registry:outcomes | |
| SURMOUNT-1 | A4 | TIRZ_SC_15MG_QW | 72 | arm, percent_change | -22.500 | 0.390 | 625 | registry:outcomes | |
| NCT04881760 | A1 | PLACEBO | 48 | arm, percent_change | -2.110 | 0.730 | 68 | registry:outcomes | |
| NCT04881760 | A2 | RETA_SC_1MG_QW | 48 | arm, percent_change | -8.670 | 0.950 | 69 | registry:outcomes | |
| NCT04881760 | A3+A4 | RETA_SC_4MG_QW | 48 | arm, percent_change | -17.075 | 1.095 | 66 | arms_combined | registry:outcomes |
| NCT04881760 | A5+A6 | RETA_SC_8MG_QW | 48 | arm, percent_change | -22.800 | 1.034 | 70 | arms_combined | registry:outcomes |
| NCT04881760 | A7 | RETA_SC_12MG_QW | 48 | arm, percent_change | -24.220 | 1.240 | 62 | registry:outcomes | |
| ATTAIN-1 | A1 | PLACEBO | 72 | arm, percent_change | -0.870 | 0.247 | 949 | registry:outcomes | |
| ATTAIN-1 | A2 | ORFO_PO_6MG_QD | 72 | arm, percent_change | -7.820 | 0.302 | 723 | registry:outcomes | |
| ATTAIN-1 | A3 | ORFO_PO_12MG_QD | 72 | arm, percent_change | -9.270 | 0.335 | 725 | registry:outcomes | |
| ATTAIN-1 | A4 | ORFO_PO_36MG_QD | 72 | arm, percent_change | -12.350 | 0.364 | 730 | registry:outcomes | |
| SURMOUNT-3 | A1 | TIRZ_SC_MTD_QW | 72 | arm, percent_change | -21.100 | 0.600 | 227 | R0007405:Results | |
| SURMOUNT-3 | A2 | PLACEBO | 72 | arm, percent_change | 3.300 | 0.600 | 202 | R0007405:Results |
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.