Network meta-analysis

Systolic blood pressure change

Overweight or obesity without diabetes (adults)

weeks 40 to 104 (target week 68)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean difference

Randomized trials

Treatments

1,086

Participants

Trial arms

In plain language

Across 2 trials with 1,086 participants, 0 of 8 treatments had a clearly better result than placebo on systolic blood pressure change, and for 8 the evidence could not tell them apart from placebo. The most favorable estimate was for Tirzepatide subcutaneous once weekly, maximum tolerated dose: 10 or 15 mg: mean difference -9.01 mmHg (95% credible interval -19.87 to 2.82).

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
Tirzepatide subcutaneous once weekly, maximum tolerated dose: 10 or 15 mg TIRZ_SC_MTD_QW	-9.01 (-19.87 to 2.82)	-24.60 to 8.03	-9.20 (-11.14 to -7.26)	Unclear
Semaglutide and bimagrumab 2.4 to 30 mg injection once weekly BIMASEMA_SC_2p4-30MG_QW	-3.49 (-14.54 to 8.06)	-19.54 to 12.78	-3.50 (-8.80 to 1.80)	Unclear
Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW	-1.70 (-13.38 to 9.82)	-18.12 to 13.88	-1.70 (-7.00 to 3.60)	Unclear
Semaglutide 2.4 mg subcutaneous once weekly SEMA_SC_2p4MG_QW	-1.09 (-12.81 to 10.28)	-18.09 to 14.69	-1.00 (-6.30 to 4.30)	Unclear
Semaglutide and bimagrumab 2.4 to 10 mg injection once weekly BIMASEMA_SC_2p4-10MG_QW	-1.06 (-13.21 to 10.00)	-17.07 to 14.32	-1.00 (-6.55 to 4.55)	Unclear
Semaglutide and bimagrumab 1.0 to 30 mg injection once weekly BIMASEMA_SC_1p0-30MG_QW	1.58 (-10.11 to 12.83)	-15.20 to 16.79	1.60 (-3.35 to 6.55)	Unclear
Semaglutide and bimagrumab 1.0 to 10 mg injection once weekly BIMASEMA_SC_1p0-10MG_QW	2.44 (-9.10 to 13.30)	-14.46 to 17.68	2.40 (-2.66 to 7.46)	Unclear
Bimagrumab OTHER_ACTIVE_bimagrumab	2.94 (-8.58 to 13.76)	-13.66 to 18.43	3.06 (-1.91 to 8.03)	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	TIRZ_SC_MTD_QW	BIMASEMA_SC_2p4-30MG_QW	SEMA_SC_1p0MG_QW	SEMA_SC_2p4MG_QW	BIMASEMA_SC_2p4-10MG_QW	BIMASEMA_SC_1p0-30MG_QW	BIMASEMA_SC_1p0-10MG_QW	OTHER_ACTIVE_bimagrumab
PLACEBO	PLACEBO	9.01 -2.82 to 19.87	3.49 -8.06 to 14.54	1.70 -9.82 to 13.38	1.09 -10.28 to 12.81	1.06 -10.00 to 13.21	-1.58 -12.83 to 10.11	-2.44 -13.30 to 9.10	-2.94 -13.76 to 8.58
TIRZ_SC_MTD_QW	-9.01 -19.87 to 2.82	TIRZ_SC_MTD_QW	-5.49 -20.63 to 10.98	-7.29 -22.59 to 9.71	-7.99 -22.96 to 8.90	-7.99 -23.04 to 9.09	-10.56 -25.43 to 5.85	-11.39 -25.88 to 5.14	-11.97 -26.82 to 4.39
BIMASEMA_SC_2p4-30MG_QW	-3.49 -14.54 to 8.06	5.49 -10.98 to 20.63	BIMASEMA_SC_2p4-30MG_QW	-1.80 -14.01 to 10.16	-2.46 -14.85 to 10.04	-2.43 -14.68 to 9.89	-5.04 -16.75 to 7.53	-5.84 -17.74 to 6.55	-6.44 -18.93 to 5.67
SEMA_SC_1p0MG_QW	-1.70 -13.38 to 9.82	7.29 -9.71 to 22.59	1.80 -10.16 to 14.01	SEMA_SC_1p0MG_QW	-0.64 -12.51 to 11.65	-0.61 -12.69 to 11.42	-3.18 -15.02 to 8.86	-3.99 -15.50 to 7.84	-4.68 -16.24 to 7.58
SEMA_SC_2p4MG_QW	-1.09 -12.81 to 10.28	7.99 -8.90 to 22.96	2.46 -10.04 to 14.85	0.64 -11.65 to 12.51	SEMA_SC_2p4MG_QW	0.05 -12.30 to 11.87	-2.60 -14.36 to 9.75	-3.38 -14.98 to 8.61	-4.01 -15.90 to 7.95
BIMASEMA_SC_2p4-10MG_QW	-1.06 -13.21 to 10.00	7.99 -9.09 to 23.04	2.43 -9.89 to 14.68	0.61 -11.42 to 12.69	-0.05 -11.87 to 12.30	BIMASEMA_SC_2p4-10MG_QW	-2.53 -14.59 to 10.11	-3.37 -15.25 to 8.53	-4.03 -16.06 to 8.21
BIMASEMA_SC_1p0-30MG_QW	1.58 -10.11 to 12.83	10.56 -5.85 to 25.43	5.04 -7.53 to 16.75	3.18 -8.86 to 15.02	2.60 -9.75 to 14.36	2.53 -10.11 to 14.59	BIMASEMA_SC_1p0-30MG_QW	-0.83 -12.71 to 10.92	-1.49 -13.58 to 10.05
BIMASEMA_SC_1p0-10MG_QW	2.44 -9.10 to 13.30	11.39 -5.14 to 25.88	5.84 -6.55 to 17.74	3.99 -7.84 to 15.50	3.38 -8.61 to 14.98	3.37 -8.53 to 15.25	0.83 -10.92 to 12.71	BIMASEMA_SC_1p0-10MG_QW	-0.66 -12.33 to 10.84
OTHER_ACTIVE_bimagrumab	2.94 -8.58 to 13.76	11.97 -4.39 to 26.82	6.44 -5.67 to 18.93	4.68 -7.58 to 16.24	4.01 -7.95 to 15.90	4.03 -8.21 to 16.06	1.49 -10.05 to 13.58	0.66 -10.84 to 12.33	OTHER_ACTIVE_bimagrumab

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 3.513 (95% CrI 0.154 to 11.947)
Residual deviance: 10.1 for 10 data points
DIC: 20.2 (pD 10.1)
Largest R-hat: 1.001
Smallest ESS: bulk 1,784, tail 3,147
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: 0.000
Q (total): 0.00 on 0 df
Q (between designs): 0.00

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; 2 of 2
NCT05616013 S000715	37.3
SURMOUNT-3 S002157	35.9

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.

FlagOutcome assessment, analysis set: confounded with design: modified_itt 1, safety 1
FlagOutcome assessment, definition: confounded with design: change in systolic blood pressure from randomization 1, not stated 1
FlagRisk of bias, blinding: confounded with design: double_blind 1, open_label 1
FlagHeterogeneity, tau above threshold: tau 3.51 exceeds the outcome threshold 2; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 48 to 72 weeks
NoteData handling, input conversions: arms_combined 1, n_randomized 2

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
NCT05616013	48	safety	not stated	not stated	not stated	not stated	hypothetical	not stated	open_label	industry	2022	adults 18 to 80; BMI 30 or more, or 27 or more with comorbidity; no diabetes (HbA1c below 6.5 percent); weight below 150 kg
SURMOUNT-3	72	modified_itt	change in systolic blood pressure from randomization	not stated	not stated	not stated	hypothetical	not stated	double_blind	industry	2021	age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; at least 5 percent loss in lead in

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
NCT05616013	A1	PLACEBO	48	arm, change	-6.900	2.100	56		R0015266:Table 2
NCT05616013	A2+A3	OTHER_ACTIVE_bimagrumab	48	arm, change	-3.843	1.422	113	arms_combined	R0015266:Table 2
NCT05616013	A4	SEMA_SC_1p0MG_QW	48	arm, change	-8.600	1.700	56		R0015266:Table 2
NCT05616013	A5	SEMA_SC_2p4MG_QW	48	arm, change	-7.900	1.700	57		R0015266:Table 2
NCT05616013	A6	BIMASEMA_SC_1p0-10MG_QW	48	arm, change	-4.500	1.500	56		R0015266:Table 2
NCT05616013	A7	BIMASEMA_SC_2p4-10MG_QW	48	arm, change	-7.900	1.900	56		R0015266:Table 2
NCT05616013	A8	BIMASEMA_SC_1p0-30MG_QW	48	arm, change	-5.300	1.400	56		R0015266:Table 2
NCT05616013	A9	BIMASEMA_SC_2p4-30MG_QW	48	arm, change	-10.400	1.700	57		R0015266:Table 2
SURMOUNT-3	A1	TIRZ_SC_MTD_QW	72	arm, change	-5.100	0.700	287	n_randomized	R0007405:Table 4
SURMOUNT-3	A2	PLACEBO	72	arm, change	4.100	0.700	292	n_randomized	R0007405:Table 4

Rerun this analysis yourself

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