Network meta-analysis

SF-36 physical component summary change

Overweight or obesity without diabetes (adults)

weeks 20 to 130 (target week 52)Hypothetical (as if everyone stayed on treatment)Doses of a drug pooledMean difference

Randomized trials

Treatments

2,979

Participants

Trial arms

In plain language

Across 3 trials with 2,979 participants, 0 of 2 treatments had a clearly better result than placebo on SF-36 physical component summary change, and for 2 the evidence could not tell them apart from placebo. The most favorable estimate was for Tirzepatide injection: mean difference 2.97 points (95% credible interval -2.06 to 7.63).

Higher 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 points. Higher 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 injection TIRZ_SC	2.97 (-2.06 to 7.63)	-5.28 to 11.18	3.01 (1.19 to 4.82)	Unclear
Standard care or no added treatment STANDARD_CARE	-0.50 (-8.73 to 7.33)	-11.29 to 9.69	-0.49 (-4.15 to 3.16)	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	STANDARD_CARE
PLACEBO	PLACEBO	-2.97 -7.63 to 2.06	0.50 -7.33 to 8.73
TIRZ_SC	2.97 -2.06 to 7.63	TIRZ_SC	3.51 -3.13 to 10.05
STANDARD_CARE	-0.50 -8.73 to 7.33	-3.51 -10.05 to 3.13	STANDARD_CARE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 2.156 (95% CrI 0.425 to 7.265)
Residual deviance: 5.1 for 5 data points
DIC: 10.2 (pD 5.0)
Largest R-hat: 1.002
Smallest ESS: bulk 2,217, tail 2,068
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 40^2); PR03 N(0, 20^2); PR07 half normal(0, 4^2) on tau

Frequentist check (netmeta)

Method: inverse variance, REML, MD
Tau: 1.237
I squared: 88%
Q (total): 8.65 on 1 df, P = 0.003
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.

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, instrument: confounded with design: not stated 1, SF-36v2 2
FlagOutcome assessment, intercurrent events (rescue): confounded with design: hypothetical 1, not stated 2
FlagRisk of bias, blinding: confounded with design: double_blind 2, single_blind 1
NoteOutcome assessment, time point: selected time points span 36 to 72 weeks
NoteOutcome assessment, definition: mixed: not stated 2, SF-36v2 physical component summary score at week 72 1
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
SURMOUNT-1	72	modified_itt	not stated	SF-36v2	not stated	not stated	hypothetical	not stated	double_blind	industry	2019	age 18 or older; BMI 30 or more, or 27 or more with a weight related complication; no diabetes
TOGETHER-PsA	36	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	single_blind	industry	2024	age 18 to 80; active psoriatic arthritis; BMI 30 or more, or 27 to 30 with a weight related comorbidity
SURMOUNT-3	72	modified_itt	SF-36v2 physical component summary score at week 72	SF-36v2	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
SURMOUNT-1	A1	PLACEBO	72	arm, change	1.620	0.250	643	n_randomized	R0006704:Table 2
SURMOUNT-1	A2+A3+A4	TIRZ_SC	72	arm, change	3.760	0.133	1,896	n_randomized;arms_combined	R0006704:Table 2
TOGETHER-PsA	A1	STANDARD_CARE	36	contrast, md					R0018951:Table 2
TOGETHER-PsA	A2	TIRZ_SC	36	contrast, md	3.500	1.046			R0018951:Table 2
SURMOUNT-3	A1	TIRZ_SC	72	arm, final	55.800	0.400	231		R0016199:Table 1
SURMOUNT-3	A2	PLACEBO	72	arm, final	51.800	0.400	209		R0016199:Table 1

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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