Network meta-analysis
Systolic blood pressure change
Overweight or obesity without diabetes (adults)
weeks 40 to 104 (target week 68)Not stated by the trialsDoses of a drug pooledMean difference
16
Randomized trials
6
Treatments
4,344
Participants
34
Trial arms
In plain language
Across 16 trials with 4,344 participants, 3 of 5 treatments had a clearly better result than placebo on systolic blood pressure change, and for 2 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide tablet: mean difference -6.00 mmHg (95% credible interval -10.41 to -1.63).
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 |
|---|---|---|---|---|
| Semaglutide tablet SEMA_PO | -6.00 (-10.41 to -1.63) | -11.83 to -0.41 | -6.00 (-10.45 to -1.55) | Better |
| Semaglutide injection SEMA_SC | -5.84 (-7.76 to -4.21) | -10.29 to -2.01 | -6.06 (-7.97 to -4.16) | Better |
| Standard care or no added treatment STANDARD_CARE | -4.20 (-9.90 to 1.07) | -10.86 to 2.01 | -4.49 (-10.10 to 1.11) | Unclear |
| Liraglutide injection LIRA_SC | -3.85 (-6.00 to -1.84) | -8.29 to 0.19 | -4.01 (-6.16 to -1.86) | Better |
| Orlistat ORLISTAT | -1.33 (-7.22 to 4.29) | -8.20 to 5.33 | -1.51 (-7.40 to 4.38) | 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 | SEMA_PO | SEMA_SC | STANDARD_CARE | LIRA_SC | ORLISTAT |
|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 6.00 1.63 to 10.41 | 5.84 4.21 to 7.76 | 4.20 -1.07 to 9.90 | 3.85 1.84 to 6.00 | 1.33 -4.29 to 7.22 |
| SEMA_PO | -6.00 -10.41 to -1.63 | SEMA_PO | -0.15 -4.70 to 4.96 | -1.76 -8.34 to 5.47 | -2.17 -6.86 to 2.91 | -4.60 -11.76 to 2.70 |
| SEMA_SC | -5.84 -7.76 to -4.21 | 0.15 -4.96 to 4.70 | SEMA_SC | -1.64 -7.19 to 4.10 | -1.99 -4.51 to 0.29 | -4.52 -10.44 to 1.34 |
| STANDARD_CARE | -4.20 -9.90 to 1.07 | 1.76 -5.47 to 8.34 | 1.64 -4.10 to 7.19 | STANDARD_CARE | -0.35 -5.51 to 4.68 | -2.86 -10.40 to 4.58 |
| LIRA_SC | -3.85 -6.00 to -1.84 | 2.17 -2.91 to 6.86 | 1.99 -0.29 to 4.51 | 0.35 -4.68 to 5.51 | LIRA_SC | -2.52 -7.77 to 2.82 |
| ORLISTAT | -1.33 -7.22 to 4.29 | 4.60 -2.70 to 11.76 | 4.52 -1.34 to 10.44 | 2.86 -4.58 to 10.40 | 2.52 -2.82 to 7.77 | ORLISTAT |
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; 11 of 16 |
|---|---|
| STEP 10 S000832 | 39.9 |
| S-LITE S000371 | 32.62 |
| BARI-STEP S000434 | 41.5 |
| NCT03038620 S000866 | 37.65 |
| STEP 3 S000988 | 38 |
| NCT00781937 S001278 | 35.6 |
| STEP7 S001288 | not reported |
| NCT01795248 S001419 | 31.35 |
| OASIS 1 S001472 | not reported |
| STEP 8 S001600 | not reported |
| STRIVE S001687 | 45.96 |
| STEP 6 S002102 | not reported |
| NCT02453711 S002317 | body weight 111.5 kg |
| S003017 S003017 | 38.05 |
| S003067 S003067 | 34.76 |
| S003075 S003075 | 30.27 |
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: not reported by 5 of 16 trials
- FlagBaseline, Baseline BMI or body weight: design means range from 34.8 (LIRA_SC vs ORLISTAT) to 39.8 (PLACEBO vs SEMA_SC) kg/m2; threshold 3
- NoteOutcome assessment, time point: selected time points span 40 to 68 weeks
- NoteOutcome assessment, analysis set: mixed: completers 3, full_analysis 8, modified_itt 2, other 2, per_protocol 1
- NoteOutcome assessment, definition: mixed: change in systolic blood pressure 2, change in systolic blood pressure from baseline (registry description) 1, not stated 13
- NoteRisk of bias, blinding: mixed: double_blind 14, open_label 1, single_blind 1
- NoteRisk of bias, funding: mixed: industry 12, mixed 4
- NoteData handling, input conversions: arms_combined 4
| Trial | instrument | time weeks | analysis set | definition | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| STEP 10 | not stated | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | Adults with obesity and prediabetes; diabetes excluded |
| S-LITE | not stated | 52 | per_protocol | not stated | not stated | not stated | not stated | not stated | double_blind | mixed | 2016 | age 18 to 65; BMI 32 to 43; no diabetes; at least 5 percent loss on 8 week low calorie diet |
| BARI-STEP | not stated | 68 | modified_itt | 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 |
| NCT03038620 | not stated | 40 | completers | change in systolic blood pressure from baseline (registry description) | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | age 35 or more; BMI 30 or more, or 27 or more with metabolic syndrome; no diabetes |
| STEP 3 | not stated | 68 | full_analysis | 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 |
| NCT00781937 | not stated | 56 | full_analysis | change in systolic blood pressure | not stated | not stated | not stated | not stated | double_blind | industry | 2008 | BMI 30 or more or 27 with comorbidity; no diabetes; at least 5 percent loss on run in |
| STEP7 | not stated | 44 | full_analysis | 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 |
| NCT01795248 | not stated | 52.18 | completers | not stated | not stated | not stated | not stated | not stated | double_blind | mixed | 2012 | women with prior gestational diabetes; no diabetes; overweight or obese |
| OASIS 1 | not stated | 68 | full_analysis | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | overweight or obesity |
| STEP 8 | not stated | 68 | full_analysis | 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 | not stated | 52 | completers | 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 | not stated | 68 | full_analysis | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2019 | |
| NCT02453711 | not stated | 52 | full_analysis | change in systolic blood pressure | not stated | not stated | not stated | not stated | double_blind | industry | 2015 | BMI 30 or more without diabetes |
| S003017 | not stated | 52.14 | other | 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 |
| S003067 | not stated | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2007 | age 18 to 65; BMI 30 to 40; FPG below 7 mmol/L; no diabetes |
| S003075 | not stated | 52 | other | not stated | not stated | not stated | not stated | not stated | single_blind | mixed | 2011 | age 18 to 65; BMI 30 to 40; healthy; fasting glucose below 7 mmol/L |
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 |
|---|---|---|---|---|---|---|---|---|---|
| S-LITE | A1+A2 | PLACEBO | 52 | arm, change | 4.020 | 1.867 | 65 | arms_combined | R0007438:Table 2 |
| S-LITE | A3+A4 | LIRA_SC | 52 | arm, change | 0.148 | 1.884 | 65 | arms_combined | R0007438:Table 2 |
| BARI-STEP | A1 | PLACEBO | 68 | arm, change | 2.000 | 3.100 | 28 | R0014003:Table 2 | |
| BARI-STEP | A2 | SEMA_SC | 68 | arm, change | -3.900 | 3.300 | 34 | R0014003:Table 2 | |
| STEP 10 | A1 | SEMA_SC | 52 | arm, change | -9.000 | 1.145 | 129 | registry:outcomes | |
| STEP 10 | A2 | PLACEBO | 52 | arm, change | -1.000 | 1.600 | 66 | registry:outcomes | |
| NCT03038620 | A1 | LIRA_SC | 40 | arm, change | -5.840 | 2.104 | 73 | registry:outcomes | |
| NCT03038620 | A2 | PLACEBO | 40 | arm, change | -0.020 | 2.159 | 55 | registry:outcomes | |
| STEP 3 | A1 | SEMA_SC | 68 | arm, change | -6.000 | 0.726 | 372 | registry:outcomes | |
| STEP 3 | A2 | PLACEBO | 68 | arm, change | -2.000 | 1.094 | 188 | registry:outcomes | |
| NCT00781937 | A1 | LIRA_SC | 56 | arm, change | 1.310 | 0.900 | 207 | registry:outcomes | |
| NCT00781937 | A2 | PLACEBO | 56 | arm, change | 4.030 | 0.870 | 206 | registry:outcomes | |
| STEP7 | A1 | SEMA_SC | 44 | arm, change | -7.000 | 0.778 | 238 | registry:outcomes | |
| STEP7 | A2 | PLACEBO | 44 | arm, change | -2.000 | 1.114 | 116 | registry:outcomes | |
| NCT01795248 | A1 | PLACEBO | 52.18 | arm, change | -6.900 | 1.633 | 45 | R0007651:Table 1 | |
| NCT01795248 | A2 | LIRA_SC | 52.18 | arm, change | -6.400 | 1.811 | 37 | R0007651:Table 1 | |
| OASIS 1 | A1 | SEMA_PO | 68 | arm, change | -7.000 | 0.786 | 317 | registry:outcomes | |
| OASIS 1 | A2 | PLACEBO | 68 | arm, change | -1.000 | 0.815 | 295 | registry:outcomes | |
| STEP 8 | A1 | SEMA_SC | 68 | arm, change | -7.000 | 1.311 | 114 | registry:outcomes | |
| STEP 8 | A2 | LIRA_SC | 68 | arm, change | -4.000 | 1.417 | 112 | registry:outcomes | |
| STEP 8 | A3 | PLACEBO | 68 | arm, change | 5.000 | 1.595 | 77 | registry:outcomes | |
| STRIVE | A1 | STANDARD_CARE | 52 | arm, change | -3.200 | 2.197 | 62 | R0020855:Table 3 | |
| STRIVE | A2 | LIRA_SC | 52 | arm, change | -3.900 | 1.416 | 139 | R0020855:Table 3 | |
| STEP 6 | A1+A2 | SEMA_SC | 68 | arm, change | -11.337 | 0.841 | 291 | arms_combined | registry:outcomes |
| STEP 6 | A3 | PLACEBO | 68 | arm, change | -5.000 | 1.500 | 100 | registry:outcomes | |
| NCT02453711 | A1+A2+A3+A4+A5+A6+A7 | SEMA_SC | 52 | arm, change | -6.468 | 0.449 | 671 | arms_combined | registry:outcomes |
| NCT02453711 | A8 | LIRA_SC | 52 | arm, change | -5.450 | 1.180 | 96 | registry:outcomes | |
| NCT02453711 | A9 | PLACEBO | 52 | arm, change | -1.580 | 1.040 | 123 | registry:outcomes | |
| S003017 | A1 | LIRA_SC | 52.14 | arm, final | 124.000 | 3.098 | 15 | R0016758:Table 1 | |
| S003017 | A2 | PLACEBO | 52.14 | arm, final | 133.000 | 4.243 | 8 | R0016758:Table 1 | |
| S003067 | A5 | LIRA_SC | 52 | contrast, md | -2.500 | 1.990 | R0025439:Supplement Table 3 | ||
| S003067 | A6 | ORLISTAT | 52 | contrast, md | R0025439:Supplement Table 3 | ||||
| S003075 | A1 | LIRA_SC | 52 | arm, change | 9.900 | 3.087 | R0018258:Results | ||
| S003075 | A2 | STANDARD_CARE | 52 | arm, change | 7.200 | 2.577 | R0018258: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.