Systolic blood pressure change
Overweight or obesity without diabetes (adults)
In plain language
Across 16 trials with 4,344 participants, 7 of 13 treatments had a clearly better result than placebo on systolic blood pressure change, and for 6 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 1.7 mg injection once weekly: mean difference -7.07 mmHg (95% credible interval -12.06 to -2.31).
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
Effects compared with Placebo
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Semaglutide 1.7 mg injection once weekly SEMA_SC_1p7MG_QW | -7.07 (-12.06 to -2.31) | -13.59 to -0.78 | -7.25 (-12.06 to -2.43) | Better |
| Semaglutide 0.4 mg injection once daily SEMA_SC_0p4MG_QD | -6.58 (-10.84 to -2.42) | -12.61 to -0.85 | -6.76 (-11.02 to -2.51) | Better |
| Semaglutide 2.4 mg subcutaneous once weekly SEMA_SC_2p4MG_QW | -6.27 (-8.59 to -4.23) | -11.04 to -1.80 | -6.43 (-8.62 to -4.23) | Better |
| Semaglutide 50 mg oral once daily (higher dose oral program) SEMA_PO_50MG_QD | -5.95 (-10.59 to -1.30) | -12.19 to 0.31 | -6.00 (-10.55 to -1.45) | Better |
| Semaglutide 0.2 mg injection once daily SEMA_SC_0p2MG_QD | -4.82 (-9.41 to -0.20) | -11.08 to 1.39 | -4.99 (-9.56 to -0.42) | Better |
| Semaglutide 0.3 mg injection once daily SEMA_SC_0p3MG_QD | -4.82 (-9.04 to -0.58) | -11.08 to 1.02 | -4.97 (-9.23 to -0.71) | Better |
| Semaglutide 0.1 mg injection once daily SEMA_SC_0p1MG_QD | -4.34 (-9.03 to 0.22) | -10.59 to 1.71 | -4.49 (-9.05 to 0.07) | Unclear |
| Liraglutide 3.0 mg subcutaneous once daily LIRA_SC_3p0MG_QD | -4.26 (-6.86 to -2.07) | -9.26 to 0.14 | -4.52 (-6.89 to -2.14) | Better |
| Standard care or no added treatment STANDARD_CARE | -3.48 (-10.36 to 3.14) | -11.59 to 4.16 | -3.82 (-10.72 to 3.09) | Unclear |
| Semaglutide 0.05 mg injection once daily SEMA_SC_0p05MG_QD | -2.99 (-7.70 to 1.46) | -9.27 to 3.11 | -3.19 (-7.77 to 1.39) | Unclear |
| Orlistat ORLISTAT | -1.82 (-8.05 to 4.09) | -9.43 to 5.20 | -2.02 (-8.07 to 4.04) | Unclear |
| Liraglutide 1.2 mg subcutaneous once daily LIRA_SC_1p2MG_QD | -0.83 (-11.92 to 10.03) | -12.41 to 10.51 | -1.12 (-12.32 to 10.09) | Unclear |
| Liraglutide 1.8 mg subcutaneous once daily LIRA_SC_1p8MG_QD | 0.51 (-5.64 to 6.63) | -6.70 to 7.92 | 0.50 (-5.71 to 6.71) | Unclear |
Ranking
League table
| Row versus column | PLACEBO | SEMA_SC_1p7MG_QW | SEMA_SC_0p4MG_QD | SEMA_SC_2p4MG_QW | SEMA_PO_50MG_QD | SEMA_SC_0p2MG_QD | SEMA_SC_0p3MG_QD | SEMA_SC_0p1MG_QD | LIRA_SC_3p0MG_QD | STANDARD_CARE | SEMA_SC_0p05MG_QD | ORLISTAT | LIRA_SC_1p2MG_QD | LIRA_SC_1p8MG_QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 7.07 2.31 to 12.06 | 6.58 2.42 to 10.84 | 6.27 4.23 to 8.59 | 5.95 1.30 to 10.59 | 4.82 0.20 to 9.41 | 4.82 0.58 to 9.04 | 4.34 -0.22 to 9.03 | 4.26 2.07 to 6.86 | 3.48 -3.14 to 10.36 | 2.99 -1.46 to 7.70 | 1.82 -4.09 to 8.05 | 0.83 -10.03 to 11.92 | -0.51 -6.63 to 5.64 |
| SEMA_SC_1p7MG_QW | -7.07 -12.06 to -2.31 | SEMA_SC_1p7MG_QW | -0.48 -6.96 to 5.90 | -0.83 -5.58 to 4.06 | -1.17 -7.85 to 5.34 | -2.26 -8.85 to 4.23 | -2.28 -8.68 to 4.05 | -2.72 -9.31 to 4.04 | -2.83 -7.96 to 2.52 | -3.58 -11.77 to 4.68 | -4.09 -10.66 to 2.39 | -5.30 -12.77 to 2.26 | -6.31 -17.81 to 5.45 | -7.57 -15.45 to -0.08 |
| SEMA_SC_0p4MG_QD | -6.58 -10.84 to -2.42 | 0.48 -5.90 to 6.96 | SEMA_SC_0p4MG_QD | -0.34 -4.81 to 4.45 | -0.65 -6.94 to 5.53 | -1.77 -6.66 to 3.34 | -1.79 -6.47 to 2.90 | -2.23 -7.29 to 2.75 | -2.31 -6.43 to 2.08 | -3.10 -10.83 to 4.63 | -3.62 -8.41 to 1.36 | -4.81 -11.65 to 2.38 | -5.69 -17.20 to 6.00 | -7.06 -14.74 to 0.41 |
| SEMA_SC_2p4MG_QW | -6.27 -8.59 to -4.23 | 0.83 -4.06 to 5.58 | 0.34 -4.45 to 4.81 | SEMA_SC_2p4MG_QW | -0.28 -5.68 to 4.48 | -1.45 -6.51 to 3.49 | -1.44 -6.18 to 3.20 | -1.92 -7.11 to 3.15 | -2.00 -4.92 to 1.01 | -2.78 -9.82 to 4.28 | -3.27 -8.24 to 1.60 | -4.51 -10.78 to 1.78 | -5.48 -16.57 to 5.80 | -6.75 -13.44 to -0.49 |
| SEMA_PO_50MG_QD | -5.95 -10.59 to -1.30 | 1.17 -5.34 to 7.85 | 0.65 -5.53 to 6.94 | 0.28 -4.48 to 5.68 | SEMA_PO_50MG_QD | -1.10 -7.74 to 5.64 | -1.14 -7.29 to 5.22 | -1.64 -8.08 to 5.21 | -1.67 -6.70 to 3.82 | -2.46 -10.51 to 5.81 | -2.94 -9.48 to 3.58 | -4.12 -11.60 to 4.00 | -5.24 -16.91 to 6.69 | -6.49 -14.13 to 1.29 |
| SEMA_SC_0p2MG_QD | -4.82 -9.41 to -0.20 | 2.26 -4.23 to 8.85 | 1.77 -3.34 to 6.66 | 1.45 -3.49 to 6.51 | 1.10 -5.64 to 7.74 | SEMA_SC_0p2MG_QD | -0.01 -4.88 to 5.04 | -0.47 -5.80 to 4.97 | -0.55 -4.97 to 4.27 | -1.38 -8.95 to 6.66 | -1.82 -7.19 to 3.56 | -3.02 -10.08 to 4.32 | -4.08 -15.32 to 7.71 | -5.27 -13.03 to 2.43 |
| SEMA_SC_0p3MG_QD | -4.82 -9.04 to -0.58 | 2.28 -4.05 to 8.68 | 1.79 -2.90 to 6.47 | 1.44 -3.20 to 6.18 | 1.14 -5.22 to 7.29 | 0.01 -5.04 to 4.88 | SEMA_SC_0p3MG_QD | -0.48 -5.51 to 4.63 | -0.54 -4.63 to 3.85 | -1.39 -8.82 to 6.43 | -1.81 -6.53 to 3.03 | -3.01 -9.84 to 3.92 | -3.97 -15.47 to 7.60 | -5.25 -13.06 to 2.11 |
| SEMA_SC_0p1MG_QD | -4.34 -9.03 to 0.22 | 2.72 -4.04 to 9.31 | 2.23 -2.75 to 7.29 | 1.92 -3.15 to 7.11 | 1.64 -5.21 to 8.08 | 0.47 -4.97 to 5.80 | 0.48 -4.63 to 5.51 | SEMA_SC_0p1MG_QD | -0.05 -4.66 to 4.63 | -0.85 -8.46 to 7.01 | -1.33 -6.59 to 3.92 | -2.57 -9.83 to 4.87 | -3.50 -14.88 to 8.05 | -4.89 -12.51 to 2.73 |
| LIRA_SC_3p0MG_QD | -4.26 -6.86 to -2.07 | 2.83 -2.52 to 7.96 | 2.31 -2.08 to 6.43 | 2.00 -1.01 to 4.92 | 1.67 -3.82 to 6.70 | 0.55 -4.27 to 4.97 | 0.54 -3.85 to 4.63 | 0.05 -4.63 to 4.66 | LIRA_SC_3p0MG_QD | -0.82 -7.22 to 5.49 | -1.30 -5.94 to 3.24 | -2.48 -8.11 to 3.11 | -3.48 -14.11 to 7.34 | -4.79 -11.40 to 1.65 |
| STANDARD_CARE | -3.48 -10.36 to 3.14 | 3.58 -4.68 to 11.77 | 3.10 -4.63 to 10.83 | 2.78 -4.28 to 9.82 | 2.46 -5.81 to 10.51 | 1.38 -6.66 to 8.95 | 1.39 -6.43 to 8.82 | 0.85 -7.01 to 8.46 | 0.82 -5.49 to 7.22 | STANDARD_CARE | -0.47 -8.50 to 7.22 | -1.70 -10.10 to 6.81 | -2.65 -11.36 to 5.94 | -4.02 -13.32 to 5.16 |
| SEMA_SC_0p05MG_QD | -2.99 -7.70 to 1.46 | 4.09 -2.39 to 10.66 | 3.62 -1.36 to 8.41 | 3.27 -1.60 to 8.24 | 2.94 -3.58 to 9.48 | 1.82 -3.56 to 7.19 | 1.81 -3.03 to 6.53 | 1.33 -3.92 to 6.59 | 1.30 -3.24 to 5.94 | 0.47 -7.22 to 8.50 | SEMA_SC_0p05MG_QD | -1.20 -8.14 to 5.90 | -2.21 -13.78 to 9.94 | -3.46 -11.65 to 4.18 |
| ORLISTAT | -1.82 -8.05 to 4.09 | 5.30 -2.26 to 12.77 | 4.81 -2.38 to 11.65 | 4.51 -1.78 to 10.78 | 4.12 -4.00 to 11.60 | 3.02 -4.32 to 10.08 | 3.01 -3.92 to 9.84 | 2.57 -4.87 to 9.83 | 2.48 -3.11 to 8.11 | 1.70 -6.81 to 10.10 | 1.20 -5.90 to 8.14 | ORLISTAT | -0.99 -13.03 to 11.13 | -2.31 -11.31 to 6.51 |
| LIRA_SC_1p2MG_QD | -0.83 -11.92 to 10.03 | 6.31 -5.45 to 17.81 | 5.69 -6.00 to 17.20 | 5.48 -5.80 to 16.57 | 5.24 -6.69 to 16.91 | 4.08 -7.71 to 15.32 | 3.97 -7.60 to 15.47 | 3.50 -8.05 to 14.88 | 3.48 -7.34 to 14.11 | 2.65 -5.94 to 11.36 | 2.21 -9.94 to 13.78 | 0.99 -11.13 to 13.03 | LIRA_SC_1p2MG_QD | -1.29 -13.87 to 11.11 |
| LIRA_SC_1p8MG_QD | 0.51 -5.64 to 6.63 | 7.57 0.08 to 15.45 | 7.06 -0.41 to 14.74 | 6.75 0.49 to 13.44 | 6.49 -1.29 to 14.13 | 5.27 -2.43 to 13.03 | 5.25 -2.11 to 13.06 | 4.89 -2.73 to 12.51 | 4.79 -1.65 to 11.40 | 4.02 -5.16 to 13.32 | 3.46 -4.18 to 11.65 | 2.31 -6.51 to 11.31 | 1.29 -11.11 to 13.87 | LIRA_SC_1p8MG_QD |
Heterogeneity, fit and convergence
Bayesian random effects (primary)
Frequentist check (netmeta)
Inconsistency
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
Fewer than ten trial comparisons, too few to judge funnel plot asymmetry.
Baseline characteristics of the trials
| Trial | Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 11 of 16 |
|---|---|
| S-LITE S000371 | 32.62 |
| BARI-STEP S000434 | 41.5 |
| STEP 10 S000832 | 39.9 |
| 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
- FlagBaseline, Baseline BMI or body weight: not reported by 5 of 16 trials
- FlagBaseline, Baseline BMI or body weight: design means range from 30.3 (LIRA_SC_1p2MG_QD vs STANDARD_CARE) to 46.0 (LIRA_SC_3p0MG_QD vs STANDARD_CARE) 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 | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S-LITE | 52 | per_protocol | not stated | 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 | 68 | modified_itt | 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 |
| STEP 10 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | Adults with obesity and prediabetes; diabetes excluded |
| NCT03038620 | 40 | completers | change in systolic blood pressure from baseline (registry description) | not stated | 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 | 68 | full_analysis | not stated | 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 | 56 | full_analysis | change in systolic blood pressure | not stated | 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 | 44 | full_analysis | not stated | 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 | 52.18 | completers | not stated | 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 | 68 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2021 | overweight or obesity |
| STEP 8 | 68 | 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 higher, or 27 with a weight related comorbidity; no type 2 diabetes |
| STRIVE | 52 | 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 |
| STEP 6 | 68 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2019 | |
| NCT02453711 | 52 | full_analysis | change in systolic blood pressure | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2015 | BMI 30 or more without diabetes |
| S003017 | 52.14 | other | 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 |
| S003067 | 52 | modified_itt | not stated | 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 | 52 | other | not stated | 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
| 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_3p0MG_QD | 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_2p4MG_QW | 68 | arm, change | -3.900 | 3.300 | 34 | R0014003:Table 2 | |
| STEP 10 | A1 | SEMA_SC_2p4MG_QW | 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_3p0MG_QD | 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_2p4MG_QW | 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_3p0MG_QD | 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_2p4MG_QW | 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_1p8MG_QD | 52.18 | arm, change | -6.400 | 1.811 | 37 | R0007651:Table 1 | |
| OASIS 1 | A1 | SEMA_PO_50MG_QD | 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_2p4MG_QW | 68 | arm, change | -7.000 | 1.311 | 114 | registry:outcomes | |
| STEP 8 | A2 | LIRA_SC_3p0MG_QD | 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_3p0MG_QD | 52 | arm, change | -3.900 | 1.416 | 139 | R0020855:Table 3 | |
| STEP 6 | A1 | SEMA_SC_1p7MG_QW | 68 | arm, change | -12.000 | 1.313 | 98 | registry:outcomes | |
| STEP 6 | A2 | SEMA_SC_2p4MG_QW | 68 | arm, change | -11.000 | 1.080 | 193 | registry:outcomes | |
| STEP 6 | A3 | PLACEBO | 68 | arm, change | -5.000 | 1.500 | 100 | registry:outcomes | |
| NCT02453711 | A1 | SEMA_SC_0p05MG_QD | 52 | arm, change | -4.460 | 1.200 | 91 | registry:outcomes | |
| NCT02453711 | A2 | SEMA_SC_0p1MG_QD | 52 | arm, change | -5.760 | 1.180 | 96 | registry:outcomes | |
| NCT02453711 | A3 | SEMA_SC_0p2MG_QD | 52 | arm, change | -6.260 | 1.190 | 94 | registry:outcomes | |
| NCT02453711 | A4+A6 | SEMA_SC_0p3MG_QD | 52 | arm, change | -6.240 | 0.839 | 190 | arms_combined | registry:outcomes |
| NCT02453711 | A5+A7 | SEMA_SC_0p4MG_QD | 52 | arm, change | -8.035 | 0.833 | 200 | arms_combined | registry:outcomes |
| NCT02453711 | A8 | LIRA_SC_3p0MG_QD | 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_3p0MG_QD | 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_3p0MG_QD | 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_1p2MG_QD | 52 | arm, change | 9.900 | 3.087 | R0018258:Results | ||
| S003075 | A2 | STANDARD_CARE | 52 | arm, change | 7.200 | 2.577 | R0018258:Results |
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