LivingGLP1
Network meta-analysis

Serious adverse events

Children and adolescents with type 2 diabetes

longest follow-upRecorded harmsEach dose separatelyHazard ratio (from event counts)
4
Randomized trials
6
Treatments
395
Participants
22
Events

In plain language

Across 4 trials with 395 participants, 0 of 5 treatments had a clearly better result than placebo on serious adverse events, and for 5 the evidence could not tell them apart from placebo. The most favorable estimate was for Dulaglutide 1.5 mg subcutaneous once weekly: hazard ratio (from event counts) 0.36 (95% credible interval 0.03 to 3.14).

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.
DULA_SC_0p75MG_QWDULA_SC_1p5MG_QWEXENER_SC_2MG_QWLIRA_SC_FLEX_0p6-1p2-1p8_QDLIXI_SC_20UG_QDPLACEBO
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.
0.020.050.10.20.250.51245102050100← favors treatmentfavors reference →Dulaglutide 1.5 mg subcutaneous …Dulaglutide 0.75 mg subcutaneous…Exenatide extended release 2 mg …Lixisenatide 20 ug subcutaneous …Liraglutide flexible dose inject…
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
TreatmentBayesian HR (95% CrI)95% prediction intervalFrequentist HR (95% CI)Verdict
Dulaglutide 1.5 mg subcutaneous once weekly
DULA_SC_1p5MG_QW
0.36 (0.03 to 3.14)0.02 to 4.14Unclear
Dulaglutide 0.75 mg subcutaneous once weekly
DULA_SC_0p75MG_QW
0.37 (0.03 to 3.08)0.03 to 4.19Unclear
Exenatide extended release 2 mg subcutaneous once weekly
EXENER_SC_2MG_QW
0.87 (0.08 to 10.66)0.06 to 13.65Unclear
Lixisenatide 20 ug subcutaneous once daily
LIXI_SC_20UG_QD
2.06 (0.07 to 92.68)0.06 to 112Unclear
Liraglutide flexible dose injection once daily
LIRA_SC_FLEX_0p6-1p2-1p8_QD
2.31 (0.52 to 10.79)0.35 to 16.02Unclear

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 columnPLACEBODULA_SC_1p5MG_QWDULA_SC_0p75MG_QWEXENER_SC_2MG_QWLIXI_SC_20UG_QDLIRA_SC_FLEX_0p6-1p2-1p8_QD
PLACEBOPLACEBO2.78
0.32 to 33.85		2.70
0.32 to 34.12		1.15
0.09 to 12.08		0.49
0.01 to 13.64		0.43
0.09 to 1.91
DULA_SC_1p5MG_QW0.36
0.03 to 3.14		DULA_SC_1p5MG_QW0.98
0.05 to 19.04		0.40
0.01 to 10.08		0.17
0.00 to 9.29		0.16
0.01 to 2.06
DULA_SC_0p75MG_QW0.37
0.03 to 3.08		1.02
0.05 to 20.16		DULA_SC_0p75MG_QW0.41
0.01 to 10.48		0.17
0.00 to 9.91		0.16
0.01 to 2.30
EXENER_SC_2MG_QW0.87
0.08 to 10.66		2.50
0.10 to 85.79		2.42
0.10 to 86.85		EXENER_SC_2MG_QW0.41
0.00 to 29.10		0.37
0.02 to 7.05
LIXI_SC_20UG_QD2.06
0.07 to 92.68		6.03
0.11 to 518		5.98
0.10 to 518		2.41
0.03 to 204		LIXI_SC_20UG_QD0.90
0.02 to 57.43
LIRA_SC_FLEX_0p6-1p2-1p8_QD2.31
0.52 to 10.79		6.45
0.49 to 124		6.36
0.43 to 116		2.67
0.14 to 41.46		1.12
0.02 to 47.71		LIRA_SC_FLEX_0p6-1p2-1p8_QD

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.355 (95% CrI 0.087 to 1.367), log scale
Residual deviance
8.0 for 9 data points
DIC
15.5 (pD 7.5)
Largest R-hat
1.001
Smallest ESS
bulk 5,054, tail 4,763
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 6.43 to 53 weeks
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
Ellipse™53safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2012age 10 to under 17; BMI above 85th percentile; HbA1c 7.0 to 11.0 (6.5 to 11.0 if treated)
NCT0155461824safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2011age 10 to below 18; HbA1c 6.5 to 11.0 (12.0 if insulin or sulfonylurea)
AWARD-PEDS26safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2016children and adolescents with type 2 diabetes
NCT028039186.43safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2017Age 10 to 17; T2D on metformin and/or basal insulin; HbA1c above 6.5 to 11 percent; BMI above 85th percentile

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
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
Ellipse™A1LIRA_SC_FLEX_0p6-1p2-1p8_QD53arm, events9 / 66registry:adverse_events
Ellipse™A2PLACEBO53arm, events4 / 69registry:adverse_events
NCT01554618A1EXENER_SC_2MG_QW24arm, events2 / 59R0017380:Table 2
NCT01554618A2PLACEBO24arm, events1 / 24R0017380:Table 2
AWARD-PEDSA1PLACEBO26arm, events3 / 51registry:adverse_events
AWARD-PEDSA2DULA_SC_0p75MG_QW26arm, events1 / 51registry:adverse_events
AWARD-PEDSA3DULA_SC_1p5MG_QW26arm, events1 / 52registry:adverse_events
NCT02803918A1LIXI_SC_20UG_QD6.43arm, events1 / 18R0009184:Table 4
NCT02803918A2PLACEBO6.43arm, events0 / 5R0009184:Table 4

Rerun this analysis yourself

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