Network meta-analysis
Percent body weight change
Overweight or obesity without diabetes (adults)
weeks 20 to 40 (target week 26)Treatment policyEach dose separatelyMean differenceConvergence criteria not all met
4
Randomized trials
15
Treatments
1,481
Participants
18
Trial arms
In plain language
Across 4 trials with 1,481 participants, 6 of 14 treatments had a clearly better result than placebo on percent body weight change, and for 8 the evidence could not tell them apart from placebo. The most favorable estimate was for Bofanglutide 24 mg injection once weekly: mean difference -14.80 percentage points (95% credible interval -20.16 to -6.51).
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 24 mg injection once weekly BOFANG_SC_24MG_QW | -14.80 (-20.16 to -6.51) | -22.77 to -3.58 | -15.54 (-18.11 to -12.97) | Better |
| Bofanglutide 48 mg injection every 2 weeks BOFANG_SC_48MG_Q2W | -14.21 (-19.55 to -6.02) | -22.35 to -3.21 | -14.94 (-17.45 to -12.43) | Better |
| Bofanglutide 24 mg injection every 2 weeks BOFANG_SC_24MG_Q2W | -11.78 (-17.21 to -3.62) | -19.98 to -0.30 | -12.51 (-15.06 to -9.96) | Better |
| Bofanglutide 18 mg injection every 2 weeks BOFANG_SC_18MG_Q2W | -10.65 (-16.26 to -2.37) | -18.60 to 0.56 | -11.40 (-13.94 to -8.86) | Better |
| Aleniglipron 120 mg tablet once daily ALENIG_PO_120MG_QD | -9.99 (-16.08 to -1.89) | -18.74 to 0.51 | -10.40 (-13.05 to -7.75) | Better |
| Aleniglipron 90 mg tablet once daily ALENIG_PO_90MG_QD | -8.82 (-15.11 to -0.47) | -17.77 to 1.79 | -9.20 (-11.88 to -6.52) | Better |
| Bofanglutide 12 mg injection every 2 weeks BOFANG_SC_12MG_Q2W | -7.88 (-13.31 to 0.38) | -15.67 to 3.77 | -8.60 (-11.18 to -6.02) | Unclear |
| Aleniglipron 45 mg tablet once daily ALENIG_PO_45MG_QD | -7.40 (-13.72 to 0.54) | -16.78 to 3.33 | -7.80 (-10.74 to -4.86) | Unclear |
| HRS-7535 180 mg tablet once daily HRS7535_PO_180MG_QD | -5.80 (-12.38 to 1.93) | -15.45 to 4.38 | -6.02 (-8.63 to -3.41) | Unclear |
| Liraglutide 3.0 mg subcutaneous once daily LIRA_SC_3p0MG_QD | -5.36 (-11.24 to 2.01) | -14.10 to 4.70 | -5.50 (-7.04 to -3.96) | Unclear |
| Cagrilintide OTHER_ACTIVE_cagrilintide | -5.26 (-11.31 to 2.03) | -14.33 to 5.10 | -5.37 (-6.53 to -4.21) | Unclear |
| HRS-7535 60 mg tablet once daily HRS7535_PO_60MG_QD | -4.11 (-10.35 to 3.21) | -12.93 to 5.98 | -4.35 (-6.96 to -1.74) | Unclear |
| HRS-7535 120 mg tablet once daily HRS7535_PO_120MG_QD | -3.49 (-10.13 to 3.82) | -12.53 to 7.00 | -3.63 (-6.24 to -1.02) | Unclear |
| HRS-7535 30 mg tablet once daily HRS7535_PO_30MG_QD | -0.66 (-7.10 to 6.96) | -10.03 to 9.79 | -0.82 (-3.40 to 1.76) | 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_24MG_QW | BOFANG_SC_48MG_Q2W | BOFANG_SC_24MG_Q2W | BOFANG_SC_18MG_Q2W | ALENIG_PO_120MG_QD | ALENIG_PO_90MG_QD | BOFANG_SC_12MG_Q2W | ALENIG_PO_45MG_QD | HRS7535_PO_180MG_QD | LIRA_SC_3p0MG_QD | OTHER_ACTIVE_cagrilintide | HRS7535_PO_60MG_QD | HRS7535_PO_120MG_QD | HRS7535_PO_30MG_QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 14.80 6.51 to 20.16 | 14.21 6.02 to 19.55 | 11.78 3.62 to 17.21 | 10.65 2.37 to 16.26 | 9.99 1.89 to 16.08 | 8.82 0.47 to 15.11 | 7.88 -0.38 to 13.31 | 7.40 -0.54 to 13.72 | 5.80 -1.93 to 12.38 | 5.36 -2.01 to 11.24 | 5.26 -2.03 to 11.31 | 4.11 -3.21 to 10.35 | 3.49 -3.82 to 10.13 | 0.66 -6.96 to 7.10 |
| BOFANG_SC_24MG_QW | -14.80 -20.16 to -6.51 | BOFANG_SC_24MG_QW | -0.59 -7.24 to 6.71 | -3.06 -10.19 to 4.23 | -4.10 -11.31 to 3.22 | -4.82 -13.67 to 5.49 | -5.94 -14.68 to 4.10 | -6.86 -13.66 to 0.40 | -7.35 -16.03 to 3.01 | -8.99 -17.92 to 1.85 | -9.48 -17.93 to 0.61 | -9.60 -17.88 to 1.17 | -10.64 -18.98 to 0.46 | -11.33 -19.72 to -0.71 | -14.17 -22.82 to -3.26 |
| BOFANG_SC_48MG_Q2W | -14.21 -19.55 to -6.02 | 0.59 -6.71 to 7.24 | BOFANG_SC_48MG_Q2W | -2.44 -9.49 to 4.64 | -3.54 -10.66 to 3.67 | -4.19 -13.40 to 5.66 | -5.37 -14.67 to 4.70 | -6.31 -13.14 to 0.81 | -6.79 -15.66 to 3.64 | -8.41 -17.30 to 2.53 | -8.91 -17.52 to 1.26 | -8.98 -17.39 to 1.41 | -10.08 -18.65 to 0.07 | -10.64 -19.23 to 0.00 | -13.53 -22.69 to -2.86 |
| BOFANG_SC_24MG_Q2W | -11.78 -17.21 to -3.62 | 3.06 -4.23 to 10.19 | 2.44 -4.64 to 9.49 | BOFANG_SC_24MG_Q2W | -1.08 -8.37 to 6.05 | -1.71 -10.84 to 8.25 | -2.93 -12.02 to 7.27 | -3.86 -10.63 to 3.06 | -4.36 -13.02 to 6.03 | -5.98 -14.78 to 4.89 | -6.46 -14.73 to 3.99 | -6.59 -14.77 to 3.77 | -7.66 -16.28 to 2.94 | -8.27 -16.81 to 2.46 | -11.12 -20.07 to -0.40 |
| BOFANG_SC_18MG_Q2W | -10.65 -16.26 to -2.37 | 4.10 -3.22 to 11.31 | 3.54 -3.67 to 10.66 | 1.08 -6.05 to 8.37 | BOFANG_SC_18MG_Q2W | -0.68 -10.04 to 9.53 | -1.86 -10.93 to 8.42 | -2.73 -9.99 to 4.51 | -3.23 -12.60 to 7.24 | -4.82 -13.90 to 6.16 | -5.38 -14.00 to 4.87 | -5.43 -13.88 to 5.06 | -6.52 -15.27 to 3.91 | -7.15 -15.80 to 3.93 | -10.02 -18.86 to 0.88 |
| ALENIG_PO_120MG_QD | -9.99 -16.08 to -1.89 | 4.82 -5.49 to 13.67 | 4.19 -5.66 to 13.40 | 1.71 -8.25 to 10.84 | 0.68 -9.53 to 10.04 | ALENIG_PO_120MG_QD | -1.16 -8.19 to 5.56 | -2.09 -12.38 to 6.89 | -2.55 -9.87 to 4.86 | -4.19 -13.73 to 5.98 | -4.67 -13.99 to 5.00 | -4.79 -13.90 to 5.25 | -5.88 -15.15 to 4.21 | -6.49 -15.92 to 3.75 | -9.29 -18.42 to 1.02 |
| ALENIG_PO_90MG_QD | -8.82 -15.11 to -0.47 | 5.94 -4.10 to 14.68 | 5.37 -4.70 to 14.67 | 2.93 -7.27 to 12.02 | 1.86 -8.42 to 10.93 | 1.16 -5.56 to 8.19 | ALENIG_PO_90MG_QD | -0.90 -11.07 to 8.18 | -1.44 -8.43 to 6.13 | -2.97 -12.44 to 7.07 | -3.53 -12.63 to 6.66 | -3.63 -12.64 to 6.64 | -4.69 -13.85 to 5.46 | -5.26 -14.84 to 5.10 | -8.17 -17.34 to 1.95 |
| BOFANG_SC_12MG_Q2W | -7.88 -13.31 to 0.38 | 6.86 -0.40 to 13.66 | 6.31 -0.81 to 13.14 | 3.86 -3.06 to 10.63 | 2.73 -4.51 to 9.99 | 2.09 -6.89 to 12.38 | 0.90 -8.18 to 11.07 | BOFANG_SC_12MG_Q2W | -0.50 -9.73 to 9.81 | -2.08 -11.00 to 8.87 | -2.62 -11.08 to 7.34 | -2.70 -10.98 to 7.52 | -3.72 -12.76 to 6.51 | -4.43 -12.80 to 6.26 | -7.21 -16.15 to 3.21 |
| ALENIG_PO_45MG_QD | -7.40 -13.72 to 0.54 | 7.35 -3.01 to 16.03 | 6.79 -3.64 to 15.66 | 4.36 -6.03 to 13.02 | 3.23 -7.24 to 12.60 | 2.55 -4.86 to 9.87 | 1.44 -6.13 to 8.43 | 0.50 -9.81 to 9.73 | ALENIG_PO_45MG_QD | -1.66 -11.27 to 8.87 | -2.14 -11.63 to 8.14 | -2.27 -11.81 to 8.06 | -3.33 -12.52 to 6.81 | -3.94 -13.30 to 6.58 | -6.75 -16.24 to 3.43 |
| HRS7535_PO_180MG_QD | -5.80 -12.38 to 1.93 | 8.99 -1.85 to 17.92 | 8.41 -2.53 to 17.30 | 5.98 -4.89 to 14.78 | 4.82 -6.16 to 13.90 | 4.19 -5.98 to 13.73 | 2.97 -7.07 to 12.44 | 2.08 -8.87 to 11.00 | 1.66 -8.87 to 11.27 | HRS7535_PO_180MG_QD | -0.52 -10.36 to 9.13 | -0.59 -10.10 to 9.46 | -1.69 -8.93 to 5.31 | -2.34 -9.27 to 5.00 | -5.15 -11.99 to 2.19 |
| LIRA_SC_3p0MG_QD | -5.36 -11.24 to 2.01 | 9.48 -0.61 to 17.93 | 8.91 -1.26 to 17.52 | 6.46 -3.99 to 14.73 | 5.38 -4.87 to 14.00 | 4.67 -5.00 to 13.99 | 3.53 -6.66 to 12.63 | 2.62 -7.34 to 11.08 | 2.14 -8.14 to 11.63 | 0.52 -9.13 to 10.36 | LIRA_SC_3p0MG_QD | -0.09 -6.69 to 6.97 | -1.19 -10.24 to 8.08 | -1.87 -10.99 to 7.80 | -4.68 -13.81 to 5.04 |
| OTHER_ACTIVE_cagrilintide | -5.26 -11.31 to 2.03 | 9.60 -1.17 to 17.88 | 8.98 -1.41 to 17.39 | 6.59 -3.77 to 14.77 | 5.43 -5.06 to 13.88 | 4.79 -5.25 to 13.90 | 3.63 -6.64 to 12.64 | 2.70 -7.52 to 10.98 | 2.27 -8.06 to 11.81 | 0.59 -9.46 to 10.10 | 0.09 -6.97 to 6.69 | OTHER_ACTIVE_cagrilintide | -1.10 -10.49 to 8.14 | -1.77 -11.38 to 8.05 | -4.60 -14.02 to 4.94 |
| HRS7535_PO_60MG_QD | -4.11 -10.35 to 3.21 | 10.64 -0.46 to 18.98 | 10.08 -0.07 to 18.65 | 7.66 -2.94 to 16.28 | 6.52 -3.91 to 15.27 | 5.88 -4.21 to 15.15 | 4.69 -5.46 to 13.85 | 3.72 -6.51 to 12.76 | 3.33 -6.81 to 12.52 | 1.69 -5.31 to 8.93 | 1.19 -8.08 to 10.24 | 1.10 -8.14 to 10.49 | HRS7535_PO_60MG_QD | -0.66 -7.58 to 6.65 | -3.52 -10.58 to 4.02 |
| HRS7535_PO_120MG_QD | -3.49 -10.13 to 3.82 | 11.33 0.71 to 19.72 | 10.64 -0.00 to 19.23 | 8.27 -2.46 to 16.81 | 7.15 -3.93 to 15.80 | 6.49 -3.75 to 15.92 | 5.26 -5.10 to 14.84 | 4.43 -6.26 to 12.80 | 3.94 -6.58 to 13.30 | 2.34 -5.00 to 9.27 | 1.87 -7.80 to 10.99 | 1.77 -8.05 to 11.38 | 0.66 -6.65 to 7.58 | HRS7535_PO_120MG_QD | -2.81 -10.05 to 4.38 |
| HRS7535_PO_30MG_QD | -0.66 -7.10 to 6.96 | 14.17 3.26 to 22.82 | 13.53 2.86 to 22.69 | 11.12 0.40 to 20.07 | 10.02 -0.88 to 18.86 | 9.29 -1.02 to 18.42 | 8.17 -1.95 to 17.34 | 7.21 -3.21 to 16.15 | 6.75 -3.43 to 16.24 | 5.15 -2.19 to 11.99 | 4.68 -5.04 to 13.81 | 4.60 -4.94 to 14.02 | 3.52 -4.02 to 10.58 | 2.81 -4.38 to 10.05 | HRS7535_PO_30MG_QD |
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; 4 of 4 | Type 2 diabetes share in weight trials (percent of participants) effect modifier; 4 of 4 | Sex (percent female) effect modifier, prognostic factor; 4 of 4 | Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 4 of 4 | Treatment duration (weeks) effect modifier; 4 of 4 | Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 4 of 4 |
|---|---|---|---|---|---|---|
| ACCESS S000899 | 39.46 | 0 population codes | 54.35 | 1.74 | 36 | not_reported |
| NCT03856047 S001532 | 37.83 | 0 population codes | 61.75 | 13.03 | 26 | standard |
| NCT06250946 S002275 | 32.5 | 0 population codes | 48.49 | 100 region: all sites in Asia | 36 | standard |
| NCT06256562 S002790 | 33.23 | 0 population codes | 45.62 | 100 | 30 | 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 32.5 (HRS7535_PO_120MG_QD vs HRS7535_PO_180MG_QD vs HRS7535_PO_30MG_QD vs HRS7535_PO_60MG_QD vs PLACEBO) to 39.5 (ALENIG_PO_120MG_QD vs ALENIG_PO_45MG_QD vs ALENIG_PO_90MG_QD vs PLACEBO) kg/m2; threshold 3
- FlagBaseline, Sex: design means range from 45.6 (BOFANG_SC_12MG_Q2W vs BOFANG_SC_18MG_Q2W vs BOFANG_SC_24MG_Q2W vs BOFANG_SC_24MG_QW vs BOFANG_SC_48MG_Q2W vs PLACEBO) to 61.7 (LIRA_SC_3p0MG_QD vs OTHER_ACTIVE_cagrilintide vs PLACEBO) percent female; threshold 15
- FlagBaseline, Asian ancestry or region: design means range from 1.7 (ALENIG_PO_120MG_QD vs ALENIG_PO_45MG_QD vs ALENIG_PO_90MG_QD vs PLACEBO) to 100.0 (BOFANG_SC_12MG_Q2W vs BOFANG_SC_18MG_Q2W vs BOFANG_SC_24MG_Q2W vs BOFANG_SC_24MG_QW vs BOFANG_SC_48MG_Q2W vs PLACEBO) percent Asian; threshold 30
- NoteOutcome assessment, time point: selected time points span 26 to 36 weeks
- NoteOutcome assessment, analysis set: mixed: full_analysis 2, modified_itt 1, randomized 1
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 3, treatment_policy 1
- NoteData handling, input conversions: arms_combined 1
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ACCESS | 36 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2024 | age 18 to 79; BMI 30 or more, or 27 or more with comorbidity; HbA1c below 6.5 percent; weight above 80 kg; no diabetes |
| NCT03856047 | 26 | 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 more, or 27 or more with hypertension or dyslipidemia; no diabetes |
| NCT06250946 | 26 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2024 | age 18 to 65; BMI 28 to 40; no diabetes, HbA1c below 6.5 percent |
| NCT06256562 | 30 | modified_itt | not stated | not stated | not stated | not stated | treatment_policy | 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 |
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 |
|---|---|---|---|---|---|---|---|---|---|
| ACCESS | A1 | ALENIG_PO_45MG_QD | 36 | arm, percent_change | -8.800 | 1.130 | 45 | R0000892:Extended Data Table 2 | |
| ACCESS | A2 | ALENIG_PO_90MG_QD | 36 | arm, percent_change | -10.200 | 0.940 | 65 | R0000892:Extended Data Table 2 | |
| ACCESS | A3 | ALENIG_PO_120MG_QD | 36 | arm, percent_change | -11.400 | 0.920 | 63 | R0000892:Extended Data Table 2 | |
| ACCESS | A4 | PLACEBO | 36 | arm, percent_change | -1.000 | 0.990 | 56 | R0000892:Extended Data Table 2 | |
| NCT03856047 | A1+A2+A3+A4+A5 | OTHER_ACTIVE_cagrilintide | 26 | arm, percent_change | -8.370 | 0.253 | 487 | arms_combined | registry:outcomes |
| NCT03856047 | A6 | LIRA_SC_3p0MG_QD | 26 | arm, percent_change | -8.500 | 0.575 | 95 | registry:outcomes | |
| NCT03856047 | A7 | PLACEBO | 26 | arm, percent_change | -3.000 | 0.534 | 95 | registry:outcomes | |
| NCT06250946 | A1 | PLACEBO | 26 | arm, percent_change | -2.540 | 0.941 | 46 | R0001289:Supplement Table S1 | |
| NCT06250946 | A2 | HRS7535_PO_30MG_QD | 26 | arm, percent_change | -3.360 | 0.921 | 48 | R0001289:Supplement Table S1 | |
| NCT06250946 | A3 | HRS7535_PO_60MG_QD | 26 | arm, percent_change | -6.890 | 0.939 | 47 | R0001289:Supplement Table S1 | |
| NCT06250946 | A4 | HRS7535_PO_120MG_QD | 26 | arm, percent_change | -6.170 | 0.941 | 46 | R0001289:Supplement Table S1 | |
| NCT06250946 | A5 | HRS7535_PO_180MG_QD | 26 | arm, percent_change | -8.560 | 0.941 | 48 | R0001289:Supplement Table S1 | |
| NCT06256562 | A1 | BOFANG_SC_12MG_Q2W | 30 | arm, percent_change | -9.750 | 0.990 | 52 | R0002409:Table 2 | |
| NCT06256562 | A2 | BOFANG_SC_18MG_Q2W | 30 | arm, percent_change | -12.550 | 0.960 | 53 | R0002409:Table 2 | |
| NCT06256562 | A3 | BOFANG_SC_24MG_Q2W | 30 | arm, percent_change | -13.660 | 0.970 | 52 | R0002409:Table 2 | |
| NCT06256562 | A4 | BOFANG_SC_48MG_Q2W | 30 | arm, percent_change | -16.090 | 0.940 | 64 | R0002409:Table 2 | |
| NCT06256562 | A5 | BOFANG_SC_24MG_QW | 30 | arm, percent_change | -16.690 | 0.980 | 53 | R0002409:Table 2 | |
| NCT06256562 | A6 | PLACEBO | 30 | arm, percent_change | -1.150 | 0.870 | 66 | R0002409:Table 2 |
Rerun this analysis yourself
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