Network meta-analysis

Serious adverse events

Children and adolescents with obesity

longest follow-upRecorded harmsEach dose separatelyHazard ratio (from event counts)

Randomized trials

Treatments

574

Participants

Events

In plain language

Across 5 trials with 574 participants, 0 of 4 treatments had a clearly better result than placebo on serious adverse events, and for 4 the evidence could not tell them apart from placebo. The most favorable estimate was for Liraglutide maximum tolerated dose injection once daily: hazard ratio (from event counts) 0.51 (95% credible interval 0.00 to 39.43).

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

Hazard ratio (from event counts). Lower values favor the treatment.

Versus Placebo, log scale. 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 HR (95% CrI)	95% prediction interval	Verdict
Liraglutide maximum tolerated dose injection once daily LIRA_SC_MTD_0p3-0p6-0p9-1p2-1p8-2p4-3p0_QD	0.51 (0.00 to 39.43)	0.00 to 45.59	Unclear
Liraglutide 3.0 mg subcutaneous once daily LIRA_SC_3p0MG_QD	0.77 (0.16 to 3.71)	0.12 to 5.82	Unclear
Semaglutide 2.4 mg subcutaneous once weekly SEMA_SC_2p4MG_QW	1.31 (0.33 to 5.40)	0.21 to 8.08	Unclear
Exenatide extended release 2 mg subcutaneous once weekly EXENER_SC_2MG_QW	2.80 (0.12 to 96.53)	0.09 to 116	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: hazard ratio (from event counts) 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_MTD_0p3-0p6-0p9-1p2-1p8-2p4-3p0_QD	LIRA_SC_3p0MG_QD	SEMA_SC_2p4MG_QW	EXENER_SC_2MG_QW
PLACEBO	PLACEBO	1.96 0.03 to 207	1.30 0.27 to 6.10	0.76 0.19 to 3.01	0.36 0.01 to 8.18
LIRA_SC_MTD_0p3-0p6-0p9-1p2-1p8-2p4-3p0_QD	0.51 0.00 to 39.43	LIRA_SC_MTD_0p3-0p6-0p9-1p2-1p8-2p4-3p0_QD	0.65 0.00 to 67.89	0.39 0.00 to 35.98	0.18 0.00 to 43.33
LIRA_SC_3p0MG_QD	0.77 0.16 to 3.71	1.53 0.01 to 212	LIRA_SC_3p0MG_QD	0.59 0.07 to 4.91	0.27 0.01 to 9.71
SEMA_SC_2p4MG_QW	1.31 0.33 to 5.40	2.56 0.03 to 339	1.69 0.20 to 13.59	SEMA_SC_2p4MG_QW	0.46 0.01 to 15.17
EXENER_SC_2MG_QW	2.80 0.12 to 96.53	5.59 0.02 to 2058	3.72 0.10 to 168	2.17 0.07 to 98.55	EXENER_SC_2MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.366 (95% CrI 0.084 to 1.425), log scale
Residual deviance: 8.4 for 10 data points
DIC: 14.4 (pD 6.0)
Largest R-hat: 1.000
Smallest ESS: bulk 4,721, tail 4,617
Divergent transitions: 0
Convergence: All criteria met
Priors: PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-1.87, 1.52^2) on tau^2 (Adverse events, pharm vs placebo control)

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.

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 9 to 75 weeks
NoteOutcome assessment, analysis set: mixed: randomized 1, safety 4
NoteRisk of bias, funding: mixed: industry 4, not_reported 1

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
NCT02527200	54	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2015	age 6 to 17; genetically confirmed Prader-Willi syndrome; BMI at least adult 30 equivalent and 95th percentile
NCT02918279	58	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2016	pubertal age 12 to under 18; BMI equivalent to adult 30 or more; poor response to lifestyle therapy
NCT02696148	9	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2016	age 7 to 11; Tanner stage 1; BMI equivalent to adult 30 or more and up to 45
NCT02496611	52	randomized	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	not_reported	2015	age 12 to below 18; BMI at least 120 percent of 95th percentile; at least 5 percent BMI loss on meal replacement
NCT04102189	75	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2019	age 12 to under 18; BMI 95th percentile or more, or 85th with a comorbidity

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the hazard ratio (from event counts) on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.

Trial data entering this analysis
Trial	Arm	Treatment	Week	Data	Events / N	Source
NCT02527200	A1	LIRA_SC_3p0MG_QD	54	arm, events	1 / 20	registry:adverse_events
NCT02527200	A2	PLACEBO	54	arm, events	0 / 12	registry:adverse_events
NCT02918279	A1	LIRA_SC_3p0MG_QD	58	arm, events	3 / 125	registry:adverse_events
NCT02918279	A2	PLACEBO	58	arm, events	5 / 126	registry:adverse_events
NCT02696148	A1	LIRA_SC_MTD_0p3-0p6-0p9-1p2-1p8-2p4-3p0_QD	9	arm, events	0 / 16	R0024666:Results
NCT02696148	A2	PLACEBO	9	arm, events	0 / 8	R0024666:Results
NCT02496611	A1	PLACEBO	52	arm, events	0 / 33	registry:adverse_events
NCT02496611	A2	EXENER_SC_2MG_QW	52	arm, events	1 / 33	registry:adverse_events
NCT04102189	A1	SEMA_SC_2p4MG_QW	75	arm, events	15 / 134	registry:adverse_events
NCT04102189	A2	PLACEBO	75	arm, events	6 / 67	registry:adverse_events

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.

Open in the NMA lab