Network meta-analysis

Percent body weight 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

1,728

Participants

Trial arms

In plain language

Across 5 trials with 1,728 participants, 2 of 6 treatments had a clearly better result than placebo on percent body weight change, and for 4 the evidence could not tell them apart from placebo. The most favorable estimate was for Retatrutide injection: mean difference -11.97 percentage points (95% credible interval -18.17 to -4.48).

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
Retatrutide injection RETA_SC	-11.97 (-18.17 to -4.48)	-20.85 to -1.27	-12.11 (-13.44 to -10.78)	Better
Alenig po ALENIG_PO	-9.81 (-16.30 to -1.69)	-19.35 to 1.12	-9.97 (-12.17 to -7.76)	Better
Liraglutide injection LIRA_SC	-5.91 (-12.23 to 1.34)	-15.16 to 4.74	-6.00 (-7.66 to -4.34)	Unclear
Cagrilintide OTHER_ACTIVE_cagrilintide	-5.38 (-11.45 to 1.61)	-14.71 to 4.75	-5.49 (-6.79 to -4.18)	Unclear
Loti po LOTI_PO	-4.41 (-10.68 to 2.28)	-14.06 to 5.59	-4.44 (-5.78 to -3.10)	Unclear
HRS-7535 tablet HRS7535_PO	-3.83 (-10.25 to 3.29)	-13.20 to 6.52	-3.90 (-5.99 to -1.81)	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	RETA_SC	ALENIG_PO	LIRA_SC	OTHER_ACTIVE_cagrilintide	LOTI_PO	HRS7535_PO
PLACEBO	PLACEBO	11.97 4.48 to 18.17	9.81 1.69 to 16.30	5.91 -1.34 to 12.23	5.38 -1.61 to 11.45	4.41 -2.28 to 10.68	3.83 -3.29 to 10.25
RETA_SC	-11.97 -18.17 to -4.48	RETA_SC	-2.14 -11.86 to 7.52	-6.03 -15.49 to 3.53	-6.56 -15.82 to 3.15	-7.57 -16.48 to 2.18	-8.01 -17.66 to 1.67
ALENIG_PO	-9.81 -16.30 to -1.69	2.14 -7.52 to 11.86	ALENIG_PO	-3.88 -13.61 to 6.12	-4.39 -13.72 to 5.75	-5.39 -14.57 to 4.96	-5.92 -15.39 to 4.38
LIRA_SC	-5.91 -12.23 to 1.34	6.03 -3.53 to 15.49	3.88 -6.12 to 13.61	LIRA_SC	-0.50 -7.56 to 6.43	-1.49 -10.66 to 8.76	-2.05 -11.44 to 7.54
OTHER_ACTIVE_cagrilintide	-5.38 -11.45 to 1.61	6.56 -3.15 to 15.82	4.39 -5.75 to 13.72	0.50 -6.43 to 7.56	OTHER_ACTIVE_cagrilintide	-0.98 -9.98 to 8.53	-1.50 -11.03 to 8.05
LOTI_PO	-4.41 -10.68 to 2.28	7.57 -2.18 to 16.48	5.39 -4.96 to 14.57	1.49 -8.76 to 10.66	0.98 -8.53 to 9.98	LOTI_PO	-0.56 -9.95 to 8.22
HRS7535_PO	-3.83 -10.25 to 3.29	8.01 -1.67 to 17.66	5.92 -4.38 to 15.39	2.05 -7.54 to 11.44	1.50 -8.05 to 11.03	0.56 -8.22 to 9.95	HRS7535_PO

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 2.163 (95% CrI 0.092 to 7.219)
Residual deviance: 10.9 for 11 data points
DIC: 21.8 (pD 10.9)
Largest R-hat: 1.002
Smallest ESS: bulk 1,779, tail 2,940
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	Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 5 of 5	Type 2 diabetes share in weight trials (percent of participants) effect modifier; 5 of 5	Sex (percent female) effect modifier, prognostic factor; 5 of 5	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 5 of 5	Treatment duration (weeks) effect modifier; 5 of 5	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 5 of 5
NCT05579977 S000448	35.44	100 population codes	52.05	13.22	32	not_reported
ACCESS S000899	39.46	0 population codes	54.35	1.74	36	not_reported
NCT03856047 S001532	37.83	0 population codes	61.75	13.03	26	standard
NCT04881760 S001653	37.34	0 population codes	48.22	1.18	48	standard
NCT06250946 S002275	32.5	0 population codes	48.49	100 region: all sites in Asia	36	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, Type 2 diabetes share in weight trials: design means range from 0.0 (ALENIG_PO vs PLACEBO) to 100.0 (LOTI_PO vs PLACEBO) percent of participants; threshold 20
FlagBaseline, Asian ancestry or region: design means range from 1.2 (PLACEBO vs RETA_SC) to 100.0 (HRS7535_PO vs PLACEBO) percent Asian; threshold 30
NoteOutcome assessment, time point: selected time points span 20 to 36 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 2, modified_itt 2, randomized 1
NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 3, not stated 2
NoteData handling, input conversions: arms_combined 5, n_randomized 2

Comparability items per trial
Trial	start year	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	funding	Eligibility
NCT05579977	2022	20	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	age 18 to 75; T2D cohort on metformin, HbA1c 7.0 to 10.0, BMI 23 or more; obesity cohort BMI 30 or more without diabetes
ACCESS	2024	36	full_analysis	not stated	not stated	not stated	not stated	hypothetical	not stated	double_blind	industry	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	2019	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	age 18 or older; BMI 30 or more, or 27 or more with hypertension or dyslipidemia; no diabetes
NCT04881760	2021	24	modified_itt	not stated	not stated	not stated	not stated	hypothetical	not stated	double_blind	industry	18 to 75 years; BMI 30 or more, or 27 to less than 30 with weight related complication; no type 2 diabetes
NCT06250946	2024	26	randomized	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	age 18 to 65; BMI 28 to 40; no diabetes, HbA1c below 6.5 percent

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
NCT05579977	A10+A11+A12+A13+A9	LOTI_PO	20	arm, percent_change	-6.284	0.301	178	arms_combined	R0004106:Supplement Table S2
NCT05579977	A8	PLACEBO	20	arm, percent_change	-1.840	0.614	45		R0004106:Supplement Table S2
ACCESS	A1+A2+A3	ALENIG_PO	36	arm, percent_change	-10.768	0.572	173	arms_combined	R0000892:Results
ACCESS	A4	PLACEBO	36	arm, percent_change	-0.800	0.969	56		R0000892:Results
NCT03856047	A1+A2+A3+A4+A5	OTHER_ACTIVE_cagrilintide	26	arm, percent_change	-8.487	0.288	506	arms_combined	R0017871:Table 2
NCT03856047	A6	LIRA_SC	26	arm, percent_change	-9.000	0.600	99		R0017871:Table 2
NCT03856047	A7	PLACEBO	26	arm, percent_change	-3.000	0.600	101		R0017871:Table 2
NCT04881760	A1	PLACEBO	24	arm, percent_change	-1.550	0.540	68		registry:outcomes
NCT04881760	A2+A3+A4+A5+A6+A7	RETA_SC	24	arm, percent_change	-13.657	0.412	267	arms_combined	registry:outcomes
NCT06250946	A1	PLACEBO	26	arm, percent_change	-2.500	0.941	46	n_randomized	R0001289:Table 2
NCT06250946	A2+A3+A4+A5	HRS7535_PO	26	arm, percent_change	-6.401	0.498	189	n_randomized;arms_combined	R0001289:Table 2

Rerun this analysis yourself

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