Network meta-analysis

SF-36 physical component summary change

Overweight or obesity without diabetes (adults)

weeks 20 to 130 (target week 52)Not stated by the trialsDoses of a drug pooledMean differenceConvergence criteria not all met

Randomized trials

Treatments

4,091

Participants

Trial arms

In plain language

Across 5 trials with 4,091 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 Liraglutide injection: mean difference 1.67 points (95% credible interval -0.06 to 3.66).

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
Liraglutide injection LIRA_SC	1.67 (-0.06 to 3.66)	-1.35 to 4.82	1.70 (1.20 to 2.19)	Unclear
Semaglutide injection SEMA_SC	0.85 (-0.32 to 2.47)	-1.76 to 4.01	0.75 (0.12 to 1.38)	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	LIRA_SC	SEMA_SC
PLACEBO	PLACEBO	-1.67 -3.66 to 0.06	-0.85 -2.47 to 0.32
LIRA_SC	1.67 -0.06 to 3.66	LIRA_SC	0.83 -1.41 to 2.72
SEMA_SC	0.85 -0.32 to 2.47	-0.83 -2.72 to 1.41	SEMA_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.640 (95% CrI 0.030 to 3.035)
Residual deviance: 11.8 for 11 data points
DIC: 20.9 (pD 9.1)
Largest R-hat: 1.002
Smallest ESS: bulk 1,594, tail 2,550
Divergent transitions: 2
Convergence: Not all met; read with caution
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: 0.000
I squared: 28%
Q (total): 5.57 on 4 df, P = 0.234
Q (between designs): 4.45, P = 0.108

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.

NoteOutcome assessment, time point: selected time points span 44 to 68 weeks
NoteOutcome assessment, definition: mixed: change in systolic blood pressure 1, not stated 4
NoteOutcome assessment, instrument: mixed: not stated 4, SF-36v2 1
NoteData handling, input conversions: arms_combined 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
NCT01272219	56	full_analysis	not stated	SF-36v2	not stated	not stated	not stated	not stated	double_blind	industry	2011	age 18 or more; BMI 30 or more, or 27 or more with hypertension or dyslipidemia; no diabetes; prediabetes allowed
STEP 3	68	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2018	BMI 30 or more, or 27 with comorbidity; no type 2 diabetes
STEP7	44	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2020	age 18 or older; BMI 30 or more, or 27 or more with a weight related comorbidity including T2D
STEP 6	68	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2019
NCT02453711	52	full_analysis	change in systolic blood pressure	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2015	BMI 30 or more 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
NCT01272219	A1	LIRA_SC	56	arm, change	3.660	0.150	1,690		R0026099:Table 2
NCT01272219	A2	PLACEBO	56	arm, change	1.930	0.210	799		R0026099:Table 2
STEP 3	A1	SEMA_SC	68	arm, change	3.200	0.297	407		registry:outcomes
STEP 3	A2	PLACEBO	68	arm, change	2.600	0.455	204		registry:outcomes
STEP7	A1	SEMA_SC	44	arm, change	1.400	0.338	237		registry:outcomes
STEP7	A2	PLACEBO	44	arm, change	0.400	0.511	116		registry:outcomes
STEP 6	A1+A2	SEMA_SC	68	arm, change	0.193	0.296	290	arms_combined	registry:outcomes
STEP 6	A3	PLACEBO	68	arm, change	0.100	0.530	100		registry:outcomes
NCT02453711	A1+A2+A3+A4+A5+A6+A7	SEMA_SC	52	arm, change	6.229	0.540	180	arms_combined	registry:outcomes
NCT02453711	A8	LIRA_SC	52	arm, change	6.210	1.020	31		registry:outcomes
NCT02453711	A9	PLACEBO	52	arm, change	2.290	1.534	37		registry:outcomes

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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