Network meta-analysis

HbA1c change

Type 2 diabetes (adults); background therapy: one or more non insulin glucose lowering drugs

weeks 36 to 64 (target week 52)Not stated by the trialsDoses of a drug pooledMean differenceSeparate part 2 of a disconnected network

Randomized trials

Treatments

926

Participants

Trial arms

In plain language

Across 2 trials with 926 participants, 0 of 3 treatments had a clearly better result than exenatide extended release injection on HbA1c change, and for 3 the evidence could not tell them apart from exenatide extended release injection. The most favorable estimate was for Exenatide extended release and dapagliflozin injection: mean difference -0.37 percentage points (95% credible interval -1.30 to 0.61).

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 Exenatide extended release injection

Mean difference in percentage points. Lower values favor the treatment.

Versus Exenatide extended release injection. 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 Exenatide extended release injection
Treatment	Bayesian MD (95% CrI)	95% prediction interval	Frequentist MD (95% CI)	Verdict
Exenatide extended release and dapagliflozin injection DAPAEXEN_SC	-0.37 (-1.30 to 0.61)	-1.73 to 1.05	-0.37 (-0.64 to -0.10)	Unclear
Dapagliflozin DAPAGLIFLOZIN	0.15 (-0.83 to 1.12)	-1.21 to 1.58	0.15 (-0.12 to 0.42)	Unclear
Basal bolus insulin OTHER_ACTIVE_basal_bolus_insulin	0.99 (-0.07 to 1.95)	-0.53 to 2.37	1.00 (0.72 to 1.28)	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	EXENER_SC	DAPAEXEN_SC	DAPAGLIFLOZIN	OTHER_ACTIVE_basal_bolus_insulin
EXENER_SC	EXENER_SC	0.37 -0.61 to 1.30	-0.15 -1.12 to 0.83	-0.99 -1.95 to 0.07
DAPAEXEN_SC	-0.37 -1.30 to 0.61	DAPAEXEN_SC	-0.51 -1.47 to 0.50	-1.35 -2.62 to 0.09
DAPAGLIFLOZIN	0.15 -0.83 to 1.12	0.51 -0.50 to 1.47	DAPAGLIFLOZIN	-0.83 -2.17 to 0.62
OTHER_ACTIVE_basal_bolus_insulin	0.99 -0.07 to 1.95	1.35 -0.09 to 2.62	0.83 -0.62 to 2.17	OTHER_ACTIVE_basal_bolus_insulin

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.311 (95% CrI 0.018 to 1.054)
Residual deviance: 5.0 for 5 data points
DIC: 10.0 (pD 5.0)
Largest R-hat: 1.001
Smallest ESS: bulk 2,610, tail 2,900
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 5^2); PR03 N(0, 2.5^2); PR07 half normal(0, 0.5^2) 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 HbA1c (percent) effect modifier, prognostic factor; 2 of 2	Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 2 of 2	Diabetes duration (years) effect modifier, prognostic factor; 2 of 2	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 1 of 2	Age (years) prognostic factor; 2 of 2	Treatment duration (weeks) effect modifier; 2 of 2
NCT02229396 S000791	9.3	S1	7.37	0.72	54.17	104
NCT02887625 S002035	10	S1	10.69	not reported	52	156.54

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 HbA1c: design means range from 9.3 (DAPAEXEN_SC vs DAPAGLIFLOZIN vs EXENER_SC) to 10.0 (EXENER_SC vs OTHER_ACTIVE_basal_bolus_insulin) percent; threshold 0.5
FlagBaseline, Diabetes duration: design means range from 7.4 (DAPAEXEN_SC vs DAPAGLIFLOZIN vs EXENER_SC) to 10.7 (EXENER_SC vs OTHER_ACTIVE_basal_bolus_insulin) years; threshold 3
FlagBaseline, Asian ancestry or region: not reported by 1 of 2 trials
FlagBaseline, Treatment duration: design means range from 104.0 (DAPAEXEN_SC vs DAPAGLIFLOZIN vs EXENER_SC) to 156.5 (EXENER_SC vs OTHER_ACTIVE_basal_bolus_insulin) weeks; threshold 26
FlagOutcome assessment, analysis set: confounded with design: modified_itt 1, other 1
FlagRisk of bias, blinding: confounded with design: double_blind 1, open_label 1
FlagRisk of bias, funding: confounded with design: industry 1, mixed 1
FlagHeterogeneity, tau above threshold: tau 0.31 exceeds the outcome threshold 0.3; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 52 to 52.14 weeks
NoteData handling, input conversions: n_randomized 3

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
NCT02229396	52	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2014	age 18 or older; HbA1c 8.0 to 12.0 percent on metformin 1500 mg/d or more
NCT02887625	52.14	other	not stated	not stated	not stated	not stated	not stated	not stated	open_label	mixed	2015	age 18 to 75; HbA1c above 7.5 percent on near maximal metformin plus sulfonylurea

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
NCT02229396	A1	DAPAEXEN_SC	52	arm, change	-1.750	0.097	231	n_randomized	R0026313:Table 3
NCT02229396	A2	EXENER_SC	52	arm, change	-1.380	0.099	231	n_randomized	R0026313:Table 3
NCT02229396	A3	DAPAGLIFLOZIN	52	arm, change	-1.230	0.097	233	n_randomized	R0026313:Table 3
NCT02887625	A1	EXENER_SC	52.14	arm, final	6.100	0.100	123		R0026120:Abstract
NCT02887625	A2	OTHER_ACTIVE_basal_bolus_insulin	52.14	arm, final	7.100	0.100	108		R0026120:Abstract

Rerun this analysis yourself

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