LivingGLP1
Network meta-analysis

Systolic blood pressure change

Overweight or obesity without diabetes (adults)

weeks 40 to 104 (target week 68)Not stated by the trialsEach dose separatelyMean difference
16
Randomized trials
14
Treatments
4,344
Participants
39
Trial arms

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

Each circle is a treatment; each line joins treatments that were randomized against each other in at least one trial.
LIRA_SC_1p2MG_QDLIRA_SC_1p8MG_QDLIRA_SC_3p0MG_QDORLISTATPLACEBOSEMA_PO_50MG_QDSEMA_SC_0p05MG_QDSEMA_SC_0p1MG_QDSEMA_SC_0p2MG_QDSEMA_SC_0p3MG_QDSEMA_SC_0p4MG_QDSEMA_SC_1p7MG_QWSEMA_SC_2p4MG_QWSTANDARD_CARE
Node area shows participants; line width shows trials comparing two treatments directly. Blue: GLP-1 receptor agonist containing treatments; grey: comparators. Hover over or tab to a node or line for details.

Effects compared with Placebo

Mean difference in mmHg. Lower values favor the treatment.
-15-10-50510← favors treatmentfavors reference →Semaglutide 1.7 mg injection onc…Semaglutide 0.4 mg injection onc…Semaglutide 2.4 mg subcutaneous …Semaglutide 50 mg oral once dail…Semaglutide 0.2 mg injection onc…Semaglutide 0.3 mg injection onc…Semaglutide 0.1 mg injection onc…Liraglutide 3.0 mg subcutaneous …Standard care or no added treatm…Semaglutide 0.05 mg injection on…OrlistatLiraglutide 1.2 mg subcutaneous …Liraglutide 1.8 mg subcutaneous …
Versus Placebo. Blue: Bayesian random effects posterior median with 95% credible interval (thick) and 95% prediction interval (dashed). Amber diamond: frequentist estimate with 95% confidence interval. Hover over or tab to a row for its values.
Effects of each treatment versus Placebo
TreatmentBayesian MD (95% CrI)95% prediction intervalFrequentist 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 7.920.50 (-5.71 to 6.71)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.
Every treatment in a row compared with every treatment in a column
Row versus columnPLACEBOSEMA_SC_1p7MG_QWSEMA_SC_0p4MG_QDSEMA_SC_2p4MG_QWSEMA_PO_50MG_QDSEMA_SC_0p2MG_QDSEMA_SC_0p3MG_QDSEMA_SC_0p1MG_QDLIRA_SC_3p0MG_QDSTANDARD_CARESEMA_SC_0p05MG_QDORLISTATLIRA_SC_1p2MG_QDLIRA_SC_1p8MG_QD
PLACEBOPLACEBO7.07
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_QD0.51
-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)

Heterogeneity (tau)
1.600 (95% CrI 0.112 to 3.972)
Residual deviance
37.9 for 38 data points
DIC
70.3 (pD 32.3)
Largest R-hat
1.006
Smallest ESS
bulk 1,188, tail 2,394
Divergent transitions
0
Convergence
All criteria met
Priors
PR01 N(0, 60^2); PR03 N(0, 30^2); PR07 half normal(0, 6^2) on tau

Frequentist check (netmeta)

Method
inverse variance, REML, MD
Tau
2.024
I squared
35%
Q (total)
15.32 on 9.99999999999999 df, P = 0.121
Q (between designs)
10.32, P = 0.035

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.
Baseline effect modifiers and prognostic factors per trial
TrialBaseline 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

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 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
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
S-LITE52per_protocolnot statednot statednot statednot statednot statednot stateddouble_blindmixed2016age 18 to 65; BMI 32 to 43; no diabetes; at least 5 percent loss on 8 week low calorie diet
BARI-STEP68modified_ittnot statednot statednot statednot statednot statednot stateddouble_blindmixed2022age 18 to 65; at least 1 year after primary bypass or sleeve; less than 20 percent weight loss from surgery
STEP 1052full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2021Adults with obesity and prediabetes; diabetes excluded
NCT0303862040completerschange in systolic blood pressure from baseline (registry description)not statednot statednot statednot statednot stateddouble_blindindustry2017age 35 or more; BMI 30 or more, or 27 or more with metabolic syndrome; no diabetes
STEP 368full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2018BMI 30 or more, or 27 with comorbidity; no type 2 diabetes
NCT0078193756full_analysischange in systolic blood pressurenot statednot statednot statednot statednot stateddouble_blindindustry2008BMI 30 or more or 27 with comorbidity; no diabetes; at least 5 percent loss on run in
STEP744full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2020age 18 or older; BMI 30 or more, or 27 or more with a weight related comorbidity including T2D
NCT0179524852.18completersnot statednot statednot statednot statednot statednot stateddouble_blindmixed2012women with prior gestational diabetes; no diabetes; overweight or obese
OASIS 168full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2021overweight or obesity
STEP 868full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2019age 18 or older; BMI 30 or higher, or 27 with a weight related comorbidity; no type 2 diabetes
STRIVE52completersnot statednot statednot statednot statednot statednot statedopen_labelindustry2017age 18 to 75; BMI 35 or more plus prediabetes, T2D, hypertension or sleep apnea; no insulin or GLP-1 RA
STEP 668full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2019
NCT0245371152full_analysischange in systolic blood pressurenot statednot statednot statednot statednot stateddouble_blindindustry2015BMI 30 or more without diabetes
S00301752.14othernot statednot statednot statednot statednot statednot stateddouble_blindindustry2019age 20 to 65; BMI above 35; 12 to 36 months after bariatric surgery with suboptimal stable weight loss or regain
S00306752modified_ittnot statednot statednot statednot statednot statednot stateddouble_blindindustry2007age 18 to 65; BMI 30 to 40; FPG below 7 mmol/L; no diabetes
S00307552othernot statednot statednot statednot statednot statednot statedsingle_blindmixed2011age 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 data entering this analysis
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
S-LITEA1+A2PLACEBO52arm, change4.0201.86765arms_combinedR0007438:Table 2
S-LITEA3+A4LIRA_SC_3p0MG_QD52arm, change0.1481.88465arms_combinedR0007438:Table 2
BARI-STEPA1PLACEBO68arm, change2.0003.10028R0014003:Table 2
BARI-STEPA2SEMA_SC_2p4MG_QW68arm, change-3.9003.30034R0014003:Table 2
STEP 10A1SEMA_SC_2p4MG_QW52arm, change-9.0001.145129registry:outcomes
STEP 10A2PLACEBO52arm, change-1.0001.60066registry:outcomes
NCT03038620A1LIRA_SC_3p0MG_QD40arm, change-5.8402.10473registry:outcomes
NCT03038620A2PLACEBO40arm, change-0.0202.15955registry:outcomes
STEP 3A1SEMA_SC_2p4MG_QW68arm, change-6.0000.726372registry:outcomes
STEP 3A2PLACEBO68arm, change-2.0001.094188registry:outcomes
NCT00781937A1LIRA_SC_3p0MG_QD56arm, change1.3100.900207registry:outcomes
NCT00781937A2PLACEBO56arm, change4.0300.870206registry:outcomes
STEP7A1SEMA_SC_2p4MG_QW44arm, change-7.0000.778238registry:outcomes
STEP7A2PLACEBO44arm, change-2.0001.114116registry:outcomes
NCT01795248A1PLACEBO52.18arm, change-6.9001.63345R0007651:Table 1
NCT01795248A2LIRA_SC_1p8MG_QD52.18arm, change-6.4001.81137R0007651:Table 1
OASIS 1A1SEMA_PO_50MG_QD68arm, change-7.0000.786317registry:outcomes
OASIS 1A2PLACEBO68arm, change-1.0000.815295registry:outcomes
STEP 8A1SEMA_SC_2p4MG_QW68arm, change-7.0001.311114registry:outcomes
STEP 8A2LIRA_SC_3p0MG_QD68arm, change-4.0001.417112registry:outcomes
STEP 8A3PLACEBO68arm, change5.0001.59577registry:outcomes
STRIVEA1STANDARD_CARE52arm, change-3.2002.19762R0020855:Table 3
STRIVEA2LIRA_SC_3p0MG_QD52arm, change-3.9001.416139R0020855:Table 3
STEP 6A1SEMA_SC_1p7MG_QW68arm, change-12.0001.31398registry:outcomes
STEP 6A2SEMA_SC_2p4MG_QW68arm, change-11.0001.080193registry:outcomes
STEP 6A3PLACEBO68arm, change-5.0001.500100registry:outcomes
NCT02453711A1SEMA_SC_0p05MG_QD52arm, change-4.4601.20091registry:outcomes
NCT02453711A2SEMA_SC_0p1MG_QD52arm, change-5.7601.18096registry:outcomes
NCT02453711A3SEMA_SC_0p2MG_QD52arm, change-6.2601.19094registry:outcomes
NCT02453711A4+A6SEMA_SC_0p3MG_QD52arm, change-6.2400.839190arms_combinedregistry:outcomes
NCT02453711A5+A7SEMA_SC_0p4MG_QD52arm, change-8.0350.833200arms_combinedregistry:outcomes
NCT02453711A8LIRA_SC_3p0MG_QD52arm, change-5.4501.18096registry:outcomes
NCT02453711A9PLACEBO52arm, change-1.5801.040123registry:outcomes
S003017A1LIRA_SC_3p0MG_QD52.14arm, final124.0003.09815R0016758:Table 1
S003017A2PLACEBO52.14arm, final133.0004.2438R0016758:Table 1
S003067A5LIRA_SC_3p0MG_QD52contrast, md-2.5001.990R0025439:Supplement Table 3
S003067A6ORLISTAT52contrast, mdR0025439:Supplement Table 3
S003075A1LIRA_SC_1p2MG_QD52arm, change9.9003.087R0018258:Results
S003075A2STANDARD_CARE52arm, change7.2002.577R0018258:Results

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