Network meta-analysis

Systolic blood pressure change

Overweight or obesity without diabetes (adults)

weeks 20 to 40 (target week 26)Hypothetical (as if everyone stayed on treatment)Doses of a drug pooledMean differenceSeparate part 2 of a disconnected network

Randomized trials

Treatments

1,389

Participants

Trial arms

In plain language

Across 4 trials with 1,389 participants, 0 of 5 treatments had a clearly better result than placebo on systolic blood pressure change, and for 5 the evidence could not tell them apart from placebo. The most favorable estimate was for Alenig po: mean difference -7.04 mmHg (95% credible interval -18.88 to 5.83).

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
Alenig po ALENIG_PO	-7.04 (-18.88 to 5.83)	-23.71 to 10.75	-7.18 (-10.60 to -3.76)	Unclear
Orforglipron tablet ORFO_PO	-6.73 (-18.52 to 5.31)	-23.26 to 10.39	-6.75 (-10.22 to -3.28)	Unclear
Cagrilintide OTHER_ACTIVE_cagrilintide	-2.25 (-14.06 to 9.77)	-19.18 to 14.82	-2.33 (-5.12 to 0.47)	Unclear
HRS-7535 tablet HRS7535_PO	-1.87 (-13.76 to 9.61)	-19.36 to 15.26	-1.84 (-4.61 to 0.93)	Unclear
Liraglutide injection LIRA_SC	-0.67 (-11.71 to 11.37)	-17.27 to 16.53	-0.70 (-4.30 to 2.90)	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	ALENIG_PO	ORFO_PO	OTHER_ACTIVE_cagrilintide	HRS7535_PO	LIRA_SC
PLACEBO	PLACEBO	7.04 -5.83 to 18.88	6.73 -5.31 to 18.52	2.25 -9.77 to 14.06	1.87 -9.61 to 13.76	0.67 -11.37 to 11.71
ALENIG_PO	-7.04 -18.88 to 5.83	ALENIG_PO	-0.26 -17.22 to 17.25	-4.76 -21.76 to 12.38	-5.16 -21.79 to 12.97	-6.33 -23.66 to 10.59
ORFO_PO	-6.73 -18.52 to 5.31	0.26 -17.25 to 17.22	ORFO_PO	-4.50 -21.68 to 11.62	-4.85 -21.32 to 11.46	-5.98 -23.41 to 10.62
OTHER_ACTIVE_cagrilintide	-2.25 -14.06 to 9.77	4.76 -12.38 to 21.76	4.50 -11.62 to 21.68	OTHER_ACTIVE_cagrilintide	-0.37 -17.22 to 17.84	-1.55 -13.68 to 10.35
HRS7535_PO	-1.87 -13.76 to 9.61	5.16 -12.97 to 21.79	4.85 -11.46 to 21.32	0.37 -17.84 to 17.22	HRS7535_PO	-1.23 -18.95 to 15.49
LIRA_SC	-0.67 -11.71 to 11.37	6.33 -10.59 to 23.66	5.98 -10.62 to 23.41	1.55 -10.35 to 13.68	1.23 -15.49 to 18.95	LIRA_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 3.867 (95% CrI 0.153 to 12.334)
Residual deviance: 8.9 for 9 data points
DIC: 17.9 (pD 8.9)
Largest R-hat: 1.001
Smallest ESS: bulk 1,980, tail 3,150
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; 4 of 4
ACCESS S000899	39.46
NCT03856047 S001532	37.83
NCT06250946 S002275	32.5
NCT05051579 S002337	38.08

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 32.5 (HRS7535_PO vs PLACEBO) to 39.5 (ALENIG_PO vs PLACEBO) kg/m2; threshold 3
FlagHeterogeneity, tau above threshold: tau 3.87 exceeds the outcome threshold 2; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 26 to 36 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 2, modified_itt 1, randomized 1
NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 3, not stated 1
NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 1, not stated 3
NoteData handling, input conversions: arms_combined 4, 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
ACCESS	36	full_analysis	not stated	not stated	not stated	not stated	hypothetical	not stated	double_blind	industry	2024	age 18 to 79; BMI 30 or more, or 27 or more with comorbidity; HbA1c below 6.5 percent; weight above 80 kg; no diabetes
NCT03856047	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2019	age 18 or older; BMI 30 or more, or 27 or more with hypertension or dyslipidemia; no diabetes
NCT06250946	26	randomized	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2024	age 18 to 65; BMI 28 to 40; no diabetes, HbA1c below 6.5 percent
NCT05051579	36	modified_itt	not stated	not stated	not stated	not stated	hypothetical	not stated	double_blind	industry	2021	adults BMI 30 or more, or 27 to 30 with a weight related complication, without 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
ACCESS	A1+A2+A3	ALENIG_PO	36	arm, change	-8.676	0.857	173	arms_combined	R0000892:Extended Data Table 5
ACCESS	A4	PLACEBO	36	arm, change	-1.500	1.520	56		R0000892:Extended Data Table 5
NCT03856047	A1+A2+A3+A4+A5	OTHER_ACTIVE_cagrilintide	26	arm, change	-5.925	0.591	506	arms_combined	R0017871:Table 2
NCT03856047	A6	LIRA_SC	26	arm, change	-4.300	1.300	99		R0017871:Table 2
NCT03856047	A7	PLACEBO	26	arm, change	-3.600	1.300	101		R0017871:Table 2
NCT06250946	A1	PLACEBO	26	arm, change	-3.250	1.260	46	n_randomized	R0001289:Supplement Table 4
NCT06250946	A2+A3+A4+A5	HRS7535_PO	26	arm, change	-5.090	0.642	189	n_randomized;arms_combined	R0001289:Supplement Table 4
NCT05051579	A1+A2+A3+A5	ORFO_PO	36	arm, change	-8.649	0.794	176	arms_combined	R0004295:Supplement Table 2
NCT05051579	A7	PLACEBO	36	arm, change	-1.900	1.582	43		R0004295:Supplement Table 2

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.

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