Network meta-analysis

Percent body weight change

Overweight or obesity without diabetes (adults)

weeks 20 to 40 (target week 26)Treatment policyDoses of a drug pooledMean difference

Randomized trials

Treatments

1,481

Participants

Trial arms

In plain language

Across 4 trials with 1,481 participants, 2 of 5 treatments had a clearly better result than placebo on percent body weight change, and for 3 the evidence could not tell them apart from placebo. The most favorable estimate was for Bofanglutide (GZR18) injection: mean difference -12.47 percentage points (95% credible interval -18.88 to -4.44).

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 percentage points. 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
Bofanglutide (GZR18) injection BOFANG_SC	-12.47 (-18.88 to -4.44)	-21.85 to -1.59	-12.71 (-14.63 to -10.78)	Better
Alenig po ALENIG_PO	-9.06 (-15.63 to -1.27)	-18.80 to 1.50	-9.27 (-11.51 to -7.03)	Better
Liraglutide injection LIRA_SC	-5.33 (-11.99 to 1.94)	-14.90 to 5.38	-5.50 (-7.04 to -3.96)	Unclear
Cagrilintide OTHER_ACTIVE_cagrilintide	-5.25 (-11.79 to 2.39)	-15.06 to 5.27	-5.37 (-6.53 to -4.21)	Unclear
HRS-7535 tablet HRS7535_PO	-3.60 (-10.51 to 3.51)	-13.70 to 6.85	-3.70 (-5.78 to -1.63)	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	BOFANG_SC	ALENIG_PO	LIRA_SC	OTHER_ACTIVE_cagrilintide	HRS7535_PO
PLACEBO	PLACEBO	12.47 4.44 to 18.88	9.06 1.27 to 15.63	5.33 -1.94 to 11.99	5.25 -2.39 to 11.79	3.60 -3.51 to 10.51
BOFANG_SC	-12.47 -18.88 to -4.44	BOFANG_SC	-3.40 -13.00 to 6.90	-7.13 -16.58 to 3.28	-7.26 -16.45 to 3.03	-8.85 -18.23 to 1.72
ALENIG_PO	-9.06 -15.63 to -1.27	3.40 -6.90 to 13.00	ALENIG_PO	-3.70 -13.51 to 6.23	-3.84 -13.26 to 6.16	-5.46 -15.34 to 4.89
LIRA_SC	-5.33 -11.99 to 1.94	7.13 -3.28 to 16.58	3.70 -6.23 to 13.51	LIRA_SC	-0.10 -7.54 to 7.04	-1.75 -11.31 to 8.37
OTHER_ACTIVE_cagrilintide	-5.25 -11.79 to 2.39	7.26 -3.03 to 16.45	3.84 -6.16 to 13.26	0.10 -7.04 to 7.54	OTHER_ACTIVE_cagrilintide	-1.61 -11.50 to 8.85
HRS7535_PO	-3.60 -10.51 to 3.51	8.85 -1.72 to 18.23	5.46 -4.89 to 15.34	1.75 -8.37 to 11.31	1.61 -8.85 to 11.50	HRS7535_PO

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 2.266 (95% CrI 0.107 to 7.355)
Residual deviance: 8.9 for 9 data points
DIC: 17.8 (pD 8.9)
Largest R-hat: 1.002
Smallest ESS: bulk 2,253, tail 3,290
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 35^2); PR03 N(0, 17.5^2); PR07 half normal(0, 3.5^2) 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	Type 2 diabetes share in weight trials (percent of participants) effect modifier; 4 of 4	Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 4 of 4	Sex (percent female) effect modifier, prognostic factor; 4 of 4	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 4 of 4	Treatment duration (weeks) effect modifier; 4 of 4	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 4 of 4
NCT06250946 S002275	0 population codes	32.5	48.49	100 region: all sites in Asia	36	standard
ACCESS S000899	0 population codes	39.46	54.35	1.74	36	not_reported
NCT03856047 S001532	0 population codes	37.83	61.75	13.03	26	standard
NCT06256562 S002790	0 population codes	33.23	45.62	100	30	standard

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
FlagBaseline, Sex: design means range from 45.6 (BOFANG_SC vs PLACEBO) to 61.7 (LIRA_SC vs OTHER_ACTIVE_cagrilintide vs PLACEBO) percent female; threshold 15
FlagBaseline, Asian ancestry or region: design means range from 1.7 (ALENIG_PO vs PLACEBO) to 100.0 (BOFANG_SC vs PLACEBO) percent Asian; threshold 30
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: not stated 3, treatment_policy 1
NoteData handling, input conversions: arms_combined 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
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
ACCESS	36	full_analysis	not stated	not stated	not stated	not stated	not stated	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	not stated	not stated	double_blind	industry	2019	age 18 or older; BMI 30 or more, or 27 or more with hypertension or dyslipidemia; no diabetes
NCT06256562	30	modified_itt	not stated	not stated	not stated	not stated	treatment_policy	not stated	double_blind	industry	2023	age 18 to 75; BMI 24 to <28 kg/m2 with comorbidity or 28 or more (Chinese criteria); 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
ACCESS	A1+A2+A3	ALENIG_PO	36	arm, percent_change	-10.273	0.571	173	arms_combined	R0000892:Extended Data Table 2
ACCESS	A4	PLACEBO	36	arm, percent_change	-1.000	0.990	56		R0000892:Extended Data Table 2
NCT03856047	A1+A2+A3+A4+A5	OTHER_ACTIVE_cagrilintide	26	arm, percent_change	-8.370	0.253	487	arms_combined	registry:outcomes
NCT03856047	A6	LIRA_SC	26	arm, percent_change	-8.500	0.575	95		registry:outcomes
NCT03856047	A7	PLACEBO	26	arm, percent_change	-3.000	0.534	95		registry:outcomes
NCT06250946	A1	PLACEBO	26	arm, percent_change	-2.540	0.941	46		R0001289:Supplement Table S1
NCT06250946	A2+A3+A4+A5	HRS7535_PO	26	arm, percent_change	-6.242	0.484	189	arms_combined	R0001289:Supplement Table S1
NCT06256562	A1+A2+A3+A4+A5	BOFANG_SC	30	arm, percent_change	-13.857	0.456	274	arms_combined	R0002409:Table 2
NCT06256562	A6	PLACEBO	30	arm, percent_change	-1.150	0.870	66		R0002409:Table 2

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