Network meta-analysis

Systolic blood pressure change

Overweight or obesity without diabetes (adults)

weeks 20 to 40 (target week 26)Not stated by the trialsDoses of a drug pooledMean difference

Randomized trials

Treatments

1,330

Participants

Trial arms

In plain language

Across 7 trials with 1,330 participants, 0 of 6 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 Exenatide extended release injection: mean difference -6.59 mmHg (95% credible interval -16.61 to 3.91).

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.

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.

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
Treatment	Bayesian MD (95% CrI)	95% prediction interval	Frequentist MD (95% CI)	Verdict
Exenatide extended release injection EXENER_SC	-6.59 (-16.61 to 3.91)	-19.90 to 7.57	-6.80 (-13.73 to 0.13)	Unclear
Mazdutide injection MAZD_SC	-6.22 (-15.24 to 2.99)	-19.17 to 6.97	-6.34 (-11.11 to -1.57)	Unclear
Liraglutide injection LIRA_SC	-4.62 (-12.59 to 1.73)	-16.78 to 5.93	-4.51 (-8.85 to -0.16)	Unclear
Efpe sc EFPE_SC	-3.13 (-12.07 to 6.16)	-16.15 to 10.14	-3.15 (-8.01 to 1.71)	Unclear
Semaglutide injection SEMA_SC	-2.77 (-10.56 to 3.56)	-14.83 to 7.95	-2.76 (-7.39 to 1.87)	Unclear
Orlistat ORLISTAT	-1.73 (-10.21 to 6.53)	-14.63 to 11.20	-1.77 (-6.83 to 3.28)	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 column	PLACEBO	EXENER_SC	MAZD_SC	LIRA_SC	EFPE_SC	SEMA_SC	ORLISTAT
PLACEBO	PLACEBO	6.59 -3.91 to 16.61	6.22 -2.99 to 15.24	4.62 -1.73 to 12.59	3.13 -6.16 to 12.07	2.77 -3.56 to 10.56	1.73 -6.53 to 10.21
EXENER_SC	-6.59 -16.61 to 3.91	EXENER_SC	-0.42 -13.90 to 12.79	-1.99 -13.64 to 11.56	-3.50 -16.70 to 10.56	-3.87 -15.39 to 10.06	-4.81 -17.60 to 8.69
MAZD_SC	-6.22 -15.24 to 2.99	0.42 -12.79 to 13.90	MAZD_SC	-1.73 -11.83 to 11.19	-3.11 -15.70 to 9.82	-3.47 -14.38 to 9.36	-4.53 -16.80 to 8.49
LIRA_SC	-4.62 -12.59 to 1.73	1.99 -11.56 to 13.64	1.73 -11.19 to 11.83	LIRA_SC	-1.42 -13.94 to 9.08	-1.81 -12.13 to 7.92	-2.74 -12.28 to 5.32
EFPE_SC	-3.13 -12.07 to 6.16	3.50 -10.56 to 16.70	3.11 -9.82 to 15.70	1.42 -9.08 to 13.94	EFPE_SC	-0.34 -11.08 to 11.90	-1.38 -13.59 to 11.30
SEMA_SC	-2.77 -10.56 to 3.56	3.87 -10.06 to 15.39	3.47 -9.36 to 14.38	1.81 -7.92 to 12.13	0.34 -11.90 to 11.08	SEMA_SC	-0.99 -12.26 to 8.93
ORLISTAT	-1.73 -10.21 to 6.53	4.81 -8.69 to 17.60	4.53 -8.49 to 16.80	2.74 -5.32 to 12.28	1.38 -11.30 to 13.59	0.99 -8.93 to 12.26	ORLISTAT

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 2.832 (95% CrI 0.134 to 9.689)
Residual deviance: 14.9 for 15 data points
DIC: 28.9 (pD 14.0)
Largest R-hat: 1.002
Smallest ESS: bulk 1,622, tail 3,504
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: 1.986
I squared: 26%
Q (total): 2.71 on 2 df, P = 0.258
Q (between designs): 1.24, P = 0.266

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
Trial	Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 7 of 7
BARI-STEP S000434	41.5
BARIOPTIMISE S000466	43.1
NCT02075281 S000743	35.44
NCT04904913 S001183	31.83
Dapalost S001235	35.4
HISTORI S001361	40.41
NCT00422058 S001402	34.76

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 31.8 (MAZD_SC vs PLACEBO) to 43.1 (LIRA_SC vs PLACEBO) kg/m2; threshold 3
FlagHeterogeneity, tau above threshold: tau 2.83 exceeds the outcome threshold 2; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 20 to 32 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 1, modified_itt 4, randomized 1, safety 1
NoteRisk of bias, funding: mixed: industry 4, mixed 3
NoteData handling, input conversions: arms_combined 3, n_randomized 4

Comparability items per trial
Trial	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	funding	start year	Eligibility
BARI-STEP	32	randomized	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
BARIOPTIMISE	24	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	mixed	2018	adults at least 1 year after RYGB or sleeve gastrectomy with 20 percent or less weight loss and suboptimal GLP-1 response
NCT02075281	20	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2014	age 18 to 64 years; BMI 30 to 42, or 27 to 30 with comorbidity; FPG below 7 mmol/L; HbA1c 6.5 percent or less; no diabetes
NCT04904913	24	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2021	Chinese adults 18 to 75; BMI 28 or more, or 24 or more with comorbidity or hyperphagia; no diabetes, HbA1c below 6.5
Dapalost	24	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2014	age 18 to 70; BMI 30 to 45 kg/m2; no diabetes
HISTORI	30	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	mixed	2022	age 18 to 60; schizophrenia spectrum on SGA; BMI 27 or more; HbA1c 39 to 47 mmol/mol; no diabetes
NCT00422058	20	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

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
Trial	Arm	Treatment	Week	Data	Value	SE	Events / N	Flags	Source
BARI-STEP	A1	PLACEBO	32	arm, change	5.010	3.100	30		R0014003:Supplement Table 3
BARI-STEP	A2	SEMA_SC	32	arm, change	-2.170	3.140	34		R0014003:Supplement Table 3
BARIOPTIMISE	A1	PLACEBO	24	arm, change	2.340	3.346	32		R0017334:Table 2
BARIOPTIMISE	A2	LIRA_SC	24	arm, change	-6.280	2.899	32		R0017334:Table 2
NCT02075281	A1	PLACEBO	20	arm, change	-0.100	1.300	48		R0011218:Supplement Table S7
NCT02075281	A2+A3+A4+A5	EFPE_SC	20	arm, change	-3.249	0.712	167	arms_combined	R0011218:Supplement Table S7
NCT04904913	A1+A2+A3	MAZD_SC	24	arm, change	-3.441	0.731	186	arms_combined	R0016107:Table 3
NCT04904913	A4	PLACEBO	24	arm, change	2.900	1.200	62		R0016107:Table 3
Dapalost	A1	EXENER_SC	24	arm, change	-9.800	2.015	25	n_randomized	R0025222:Table 1
Dapalost	A2	PLACEBO	24	arm, change	-3.000	2.117	25	n_randomized	R0025627:Table 2
HISTORI	A1	SEMA_SC	30	arm, change	-1.610	1.000	77	n_randomized	R0014539:Table 2
HISTORI	A2	PLACEBO	30	arm, change	-0.230	1.538	77	n_randomized	R0014539:Table 2
NCT00422058	A1	PLACEBO	20	arm, change	-3.200	1.372	94		registry:outcomes
NCT00422058	A2+A3+A4+A5	LIRA_SC	20	arm, change	-6.622	0.620	351	arms_combined	registry:outcomes
NCT00422058	A6	ORLISTAT	20	arm, change	-4.300	1.149	90		registry:outcomes

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.

Open in the NMA lab