Network meta-analysis
Systolic blood pressure change
Overweight or obesity without diabetes (adults)
weeks 20 to 40 (target week 26)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean differenceSeparate part 2 of a disconnected network
4
Randomized trials
14
Treatments
1,389
Participants
17
Trial arms
In plain language
Across 4 trials with 1,389 participants, 0 of 13 treatments had a clearly better result than placebo on systolic blood pressure change, and for 13 the evidence could not tell them apart from placebo. The most favorable estimate was for Orforglipron 45 mg oral once daily: mean difference -8.38 mmHg (95% credible interval -18.54 to 3.47).
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 mmHg. Lower values favor the treatment.
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Orforglipron 45 mg oral once daily ORFO_PO_45MG_QD | -8.38 (-18.54 to 3.47) | -22.83 to 8.20 | -8.70 (-13.01 to -4.39) | Unclear |
| Orforglipron 36 mg oral once daily ORFO_PO_36MG_QD | -7.79 (-17.37 to 3.93) | -22.00 to 8.86 | -8.10 (-12.41 to -3.79) | Unclear |
| Aleniglipron 120 mg tablet once daily ALENIG_PO_120MG_QD | -7.17 (-17.70 to 4.32) | -21.91 to 8.46 | -7.50 (-11.55 to -3.45) | Unclear |
| Aleniglipron 90 mg tablet once daily ALENIG_PO_90MG_QD | -7.01 (-16.98 to 4.83) | -21.32 to 10.08 | -7.40 (-11.48 to -3.32) | Unclear |
| Aleniglipron 45 mg tablet once daily ALENIG_PO_45MG_QD | -6.06 (-16.05 to 5.54) | -20.49 to 10.65 | -6.40 (-10.88 to -1.92) | Unclear |
| Orforglipron 12 mg oral once daily ORFO_PO_12MG_QD | -4.88 (-15.02 to 7.20) | -19.67 to 11.35 | -5.20 (-9.66 to -0.74) | Unclear |
| Orforglipron 24 mg oral once daily ORFO_PO_24MG_QD | -4.30 (-14.32 to 7.64) | -18.65 to 12.39 | -4.60 (-9.06 to -0.14) | Unclear |
| HRS-7535 120 mg tablet once daily HRS7535_PO_120MG_QD | -2.59 (-13.51 to 8.26) | -17.95 to 13.74 | -2.59 (-6.11 to 0.93) | Unclear |
| HRS-7535 180 mg tablet once daily HRS7535_PO_180MG_QD | -2.52 (-13.05 to 8.43) | -17.96 to 13.02 | -2.61 (-6.14 to 0.92) | Unclear |
| Cagrilintide OTHER_ACTIVE_cagrilintide | -2.35 (-12.41 to 8.07) | -16.78 to 13.23 | -2.33 (-5.12 to 0.47) | Unclear |
| HRS-7535 60 mg tablet once daily HRS7535_PO_60MG_QD | -1.27 (-11.67 to 9.18) | -15.89 to 14.10 | -1.34 (-4.85 to 2.17) | Unclear |
| HRS-7535 30 mg tablet once daily HRS7535_PO_30MG_QD | -0.83 (-11.97 to 9.94) | -16.25 to 14.43 | -0.84 (-4.42 to 2.74) | Unclear |
| Liraglutide 3.0 mg subcutaneous once daily LIRA_SC_3p0MG_QD | -0.69 (-11.18 to 10.27) | -16.02 to 15.03 | -0.70 (-4.30 to 2.90) | 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 | ORFO_PO_45MG_QD | ORFO_PO_36MG_QD | ALENIG_PO_120MG_QD | ALENIG_PO_90MG_QD | ALENIG_PO_45MG_QD | ORFO_PO_12MG_QD | ORFO_PO_24MG_QD | HRS7535_PO_120MG_QD | HRS7535_PO_180MG_QD | OTHER_ACTIVE_cagrilintide | HRS7535_PO_60MG_QD | HRS7535_PO_30MG_QD | LIRA_SC_3p0MG_QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 8.38 -3.47 to 18.54 | 7.79 -3.93 to 17.37 | 7.17 -4.32 to 17.70 | 7.01 -4.83 to 16.98 | 6.06 -5.54 to 16.05 | 4.88 -7.20 to 15.02 | 4.30 -7.64 to 14.32 | 2.59 -8.26 to 13.51 | 2.52 -8.43 to 13.05 | 2.35 -8.07 to 12.41 | 1.27 -9.18 to 11.67 | 0.83 -9.94 to 11.97 | 0.69 -10.27 to 11.18 |
| ORFO_PO_45MG_QD | -8.38 -18.54 to 3.47 | ORFO_PO_45MG_QD | -0.58 -12.10 to 10.77 | -1.19 -17.38 to 14.76 | -1.29 -16.86 to 13.73 | -2.33 -17.54 to 13.02 | -3.44 -15.10 to 8.55 | -4.10 -15.70 to 7.40 | -5.85 -20.55 to 10.99 | -5.91 -20.71 to 10.07 | -6.04 -20.47 to 9.33 | -7.09 -21.63 to 8.77 | -7.53 -22.00 to 8.74 | -7.68 -22.12 to 7.77 |
| ORFO_PO_36MG_QD | -7.79 -17.37 to 3.93 | 0.58 -10.77 to 12.10 | ORFO_PO_36MG_QD | -0.59 -15.18 to 15.58 | -0.74 -15.37 to 14.50 | -1.71 -16.61 to 13.70 | -2.87 -14.17 to 8.96 | -3.53 -14.57 to 7.78 | -5.23 -19.19 to 10.65 | -5.34 -19.22 to 10.66 | -5.43 -19.19 to 9.78 | -6.51 -20.34 to 8.60 | -6.96 -21.33 to 9.83 | -7.05 -21.25 to 8.72 |
| ALENIG_PO_120MG_QD | -7.17 -17.70 to 4.32 | 1.19 -14.76 to 17.38 | 0.59 -15.58 to 15.18 | ALENIG_PO_120MG_QD | -0.20 -11.78 to 11.14 | -1.10 -12.86 to 10.22 | -2.32 -18.42 to 13.05 | -2.82 -18.63 to 12.83 | -4.60 -19.28 to 11.26 | -4.71 -19.08 to 10.58 | -4.84 -19.59 to 10.87 | -5.96 -19.94 to 9.78 | -6.32 -20.89 to 9.84 | -6.54 -21.12 to 9.19 |
| ALENIG_PO_90MG_QD | -7.01 -16.98 to 4.83 | 1.29 -13.73 to 16.86 | 0.74 -14.50 to 15.37 | 0.20 -11.14 to 11.78 | ALENIG_PO_90MG_QD | -0.97 -12.52 to 11.27 | -2.19 -16.94 to 12.97 | -2.74 -18.21 to 12.82 | -4.48 -19.40 to 11.78 | -4.58 -18.46 to 11.27 | -4.73 -18.50 to 10.99 | -5.69 -20.37 to 10.26 | -6.26 -20.35 to 10.46 | -6.34 -20.85 to 10.06 |
| ALENIG_PO_45MG_QD | -6.06 -16.05 to 5.54 | 2.33 -13.02 to 17.54 | 1.71 -13.70 to 16.61 | 1.10 -10.22 to 12.86 | 0.97 -11.27 to 12.52 | ALENIG_PO_45MG_QD | -1.13 -16.70 to 14.22 | -1.76 -17.51 to 13.91 | -3.51 -17.95 to 12.94 | -3.47 -17.70 to 12.26 | -3.76 -18.22 to 12.24 | -4.71 -18.77 to 11.10 | -5.25 -19.27 to 10.80 | -5.40 -19.99 to 10.59 |
| ORFO_PO_12MG_QD | -4.88 -15.02 to 7.20 | 3.44 -8.55 to 15.10 | 2.87 -8.96 to 14.17 | 2.32 -13.05 to 18.42 | 2.19 -12.97 to 16.94 | 1.13 -14.22 to 16.70 | ORFO_PO_12MG_QD | -0.59 -11.98 to 10.85 | -2.40 -16.86 to 14.14 | -2.38 -17.17 to 13.69 | -2.59 -17.01 to 13.16 | -3.59 -18.09 to 12.06 | -4.07 -18.84 to 12.22 | -4.19 -18.98 to 12.03 |
| ORFO_PO_24MG_QD | -4.30 -14.32 to 7.64 | 4.10 -7.40 to 15.70 | 3.53 -7.78 to 14.57 | 2.82 -12.83 to 18.63 | 2.74 -12.82 to 18.21 | 1.76 -13.91 to 17.51 | 0.59 -10.85 to 11.98 | ORFO_PO_24MG_QD | -1.81 -15.82 to 14.45 | -1.88 -15.96 to 13.68 | -1.98 -16.19 to 13.11 | -2.94 -17.72 to 12.03 | -3.50 -17.64 to 12.72 | -3.61 -18.05 to 11.64 |
| HRS7535_PO_120MG_QD | -2.59 -13.51 to 8.26 | 5.85 -10.99 to 20.55 | 5.23 -10.65 to 19.19 | 4.60 -11.26 to 19.28 | 4.48 -11.78 to 19.40 | 3.51 -12.94 to 17.95 | 2.40 -14.14 to 16.86 | 1.81 -14.45 to 15.82 | HRS7535_PO_120MG_QD | -0.03 -11.02 to 10.51 | -0.21 -15.19 to 14.18 | -1.25 -12.32 to 9.95 | -1.70 -13.19 to 9.61 | -1.90 -17.46 to 13.42 |
| HRS7535_PO_180MG_QD | -2.52 -13.05 to 8.43 | 5.91 -10.07 to 20.71 | 5.34 -10.66 to 19.22 | 4.71 -10.58 to 19.08 | 4.58 -11.27 to 18.46 | 3.47 -12.26 to 17.70 | 2.38 -13.69 to 17.17 | 1.88 -13.68 to 15.96 | 0.03 -10.51 to 11.02 | HRS7535_PO_180MG_QD | -0.16 -14.85 to 14.18 | -1.26 -12.67 to 10.27 | -1.71 -12.72 to 10.03 | -1.89 -16.70 to 13.26 |
| OTHER_ACTIVE_cagrilintide | -2.35 -12.41 to 8.07 | 6.04 -9.33 to 20.47 | 5.43 -9.78 to 19.19 | 4.84 -10.87 to 19.59 | 4.73 -10.99 to 18.50 | 3.76 -12.24 to 18.22 | 2.59 -13.16 to 17.01 | 1.98 -13.11 to 16.19 | 0.21 -14.18 to 15.19 | 0.16 -14.18 to 14.85 | OTHER_ACTIVE_cagrilintide | -0.97 -15.89 to 13.61 | -1.57 -15.49 to 13.90 | -1.67 -12.62 to 9.61 |
| HRS7535_PO_60MG_QD | -1.27 -11.67 to 9.18 | 7.09 -8.77 to 21.63 | 6.51 -8.60 to 20.34 | 5.96 -9.78 to 19.94 | 5.69 -10.26 to 20.37 | 4.71 -11.10 to 18.77 | 3.59 -12.06 to 18.09 | 2.94 -12.03 to 17.72 | 1.25 -9.95 to 12.32 | 1.26 -10.27 to 12.67 | 0.97 -13.61 to 15.89 | HRS7535_PO_60MG_QD | -0.50 -11.68 to 10.95 | -0.61 -15.44 to 14.50 |
| HRS7535_PO_30MG_QD | -0.83 -11.97 to 9.94 | 7.53 -8.74 to 22.00 | 6.96 -9.83 to 21.33 | 6.32 -9.84 to 20.89 | 6.26 -10.46 to 20.35 | 5.25 -10.80 to 19.27 | 4.07 -12.22 to 18.84 | 3.50 -12.72 to 17.64 | 1.70 -9.61 to 13.19 | 1.71 -10.03 to 12.72 | 1.57 -13.90 to 15.49 | 0.50 -10.95 to 11.68 | HRS7535_PO_30MG_QD | -0.14 -14.91 to 14.76 |
| LIRA_SC_3p0MG_QD | -0.69 -11.18 to 10.27 | 7.68 -7.77 to 22.12 | 7.05 -8.72 to 21.25 | 6.54 -9.19 to 21.12 | 6.34 -10.06 to 20.85 | 5.40 -10.59 to 19.99 | 4.19 -12.03 to 18.98 | 3.61 -11.64 to 18.05 | 1.90 -13.42 to 17.46 | 1.89 -13.26 to 16.70 | 1.67 -9.61 to 12.62 | 0.61 -14.50 to 15.44 | 0.14 -14.76 to 14.91 | LIRA_SC_3p0MG_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 |
|---|---|
| ACCESS S000899 | 39.46 |
| NCT03856047 S001532 | 37.83 |
| NCT06250946 S002275 | 32.5 |
| NCT05051579 S002337 | 38.08 |
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
- FlagHeterogeneity, tau above threshold: tau 3.45 exceeds the outcome threshold 2; the flags of this network are candidate explanations
- 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: hypothetical 3, not stated 1
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 1, not stated 3
- NoteData handling, input conversions: arms_combined 1, n_randomized 5
| 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 | hypothetical | 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 | hypothetical | hypothetical | 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 |
| NCT05051579 | 36 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | not stated | double_blind | industry | 2021 | adults BMI 30 or more, or 27 to 30 with a weight related complication, without 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, change | -7.900 | 1.710 | 45 | R0000892:Extended Data Table 5 | |
| ACCESS | A2 | ALENIG_PO_90MG_QD | 36 | arm, change | -8.900 | 1.420 | 65 | R0000892:Extended Data Table 5 | |
| ACCESS | A3 | ALENIG_PO_120MG_QD | 36 | arm, change | -9.000 | 1.400 | 63 | R0000892:Extended Data Table 5 | |
| ACCESS | A4 | PLACEBO | 36 | arm, change | -1.500 | 1.520 | 56 | R0000892:Extended Data Table 5 | |
| NCT03856047 | A1+A2+A3+A4+A5 | OTHER_ACTIVE_cagrilintide | 26 | arm, change | -5.925 | 0.591 | 506 | arms_combined | R0017871:Table 2 |
| NCT03856047 | A6 | LIRA_SC_3p0MG_QD | 26 | arm, change | -4.300 | 1.300 | 99 | R0017871:Table 2 | |
| NCT03856047 | A7 | PLACEBO | 26 | arm, change | -3.600 | 1.300 | 101 | R0017871:Table 2 | |
| NCT06250946 | A1 | PLACEBO | 26 | arm, change | -3.250 | 1.260 | 46 | n_randomized | R0001289:Supplement Table 4 |
| NCT06250946 | A2 | HRS7535_PO_30MG_QD | 26 | arm, change | -4.090 | 1.319 | 48 | n_randomized | R0001289:Supplement Table 4 |
| NCT06250946 | A3 | HRS7535_PO_60MG_QD | 26 | arm, change | -4.590 | 1.270 | 47 | n_randomized | R0001289:Supplement Table 4 |
| NCT06250946 | A4 | HRS7535_PO_120MG_QD | 26 | arm, change | -5.840 | 1.281 | 46 | n_randomized | R0001289:Supplement Table 4 |
| NCT06250946 | A5 | HRS7535_PO_180MG_QD | 26 | arm, change | -5.860 | 1.283 | 48 | n_randomized | R0001289:Supplement Table 4 |
| NCT05051579 | A1 | ORFO_PO_12MG_QD | 36 | arm, change | -7.100 | 1.633 | 42 | R0004295:Supplement Table 2 | |
| NCT05051579 | A2 | ORFO_PO_24MG_QD | 36 | arm, change | -6.500 | 1.633 | 41 | R0004295:Supplement Table 2 | |
| NCT05051579 | A3 | ORFO_PO_36MG_QD | 36 | arm, change | -10.000 | 1.531 | 47 | R0004295:Supplement Table 2 | |
| NCT05051579 | A5 | ORFO_PO_45MG_QD | 36 | arm, change | -10.600 | 1.531 | 46 | R0004295:Supplement Table 2 | |
| NCT05051579 | A7 | PLACEBO | 36 | arm, change | -1.900 | 1.582 | 43 | R0004295:Supplement Table 2 |
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.