Network meta-analysis

HbA1c change

Type 2 diabetes (adults); background therapy: prandial, premixed or basal bolus insulin with or without other drugs

weeks 36 to 64 (target week 52)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean difference

Randomized trials

Treatments

1,239

Participants

Trial arms

In plain language

Across 2 trials with 1,239 participants, 0 of 2 treatments had a clearly better result than dulaglutide 0.75 mg subcutaneous once weekly on HbA1c change, and for 2 the evidence could not tell them apart from dulaglutide 0.75 mg subcutaneous once weekly. The most favorable estimate was for Dulaglutide 1.5 mg subcutaneous once weekly: mean difference -0.03 percentage points (95% credible interval -0.40 to 0.33).

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 Dulaglutide 0.75 mg subcutaneous once weekly

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

Versus Dulaglutide 0.75 mg subcutaneous once weekly. 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 Dulaglutide 0.75 mg subcutaneous once weekly
Treatment	Bayesian MD (95% CrI)	95% prediction interval	Frequentist MD (95% CI)	Verdict
Dulaglutide 1.5 mg subcutaneous once weekly DULA_SC_1p5MG_QW	-0.03 (-0.40 to 0.33)	-0.64 to 0.58	-0.04 (-0.21 to 0.14)	Unclear
Insulin glargine INS_GLARGINE	0.15 (-0.26 to 0.49)	-0.49 to 0.76	0.15 (-0.02 to 0.33)	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	DULA_SC_0p75MG_QW	DULA_SC_1p5MG_QW	INS_GLARGINE
DULA_SC_0p75MG_QW	DULA_SC_0p75MG_QW	0.03 -0.33 to 0.40	-0.15 -0.49 to 0.26
DULA_SC_1p5MG_QW	-0.03 -0.40 to 0.33	DULA_SC_1p5MG_QW	-0.18 -0.52 to 0.22
INS_GLARGINE	0.15 -0.26 to 0.49	0.18 -0.22 to 0.52	INS_GLARGINE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.112 (95% CrI 0.005 to 0.618)
Residual deviance: 5.2 for 6 data points
DIC: 10.1 (pD 5.0)
Largest R-hat: 1.003
Smallest ESS: bulk 1,908, tail 2,221
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
I squared: 0%
Q (total): 0.70 on 2 df, P = 0.706

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.

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; 2 of 2	Age (years) prognostic factor; 2 of 2	Treatment duration (weeks) effect modifier; 2 of 2
AWARD-7 S000237	8.6	S3	18.1	3.01	64.57	52
NCT01191268 S001198	8.46	S3	12.73	3.96	59.36	52

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, intercurrent events (discontinuation): mixed: hypothetical 1, not stated 1
NoteRisk of bias, blinding: mixed: open_label 1, single_blind 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
AWARD-7	52	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	single_blind	industry	2012	adults with T2D and CKD stage 3 to 4 (eGFR 15 to below 60); HbA1c 7.5 to 10.5 percent on insulin; maximal ACEI or ARB; BMI 23 to 45
NCT01191268	52	modified_itt	not stated	not stated	not stated	not stated	not stated	hypothetical	open_label	industry	2010	adults with type 2 diabetes on conventional insulin with or without metformin

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	Source
AWARD-7	A1	INS_GLARGINE	52	arm, change	-1.000	0.100	153	R0017387:Abstract
AWARD-7	A2	DULA_SC_0p75MG_QW	52	arm, change	-1.100	0.100	132	R0017387:Abstract
AWARD-7	A3	DULA_SC_1p5MG_QW	52	arm, change	-1.100	0.100	130	R0017387:Abstract
NCT01191268	A1	DULA_SC_1p5MG_QW	52	arm, change	-1.480	0.080	273	registry:outcomes
NCT01191268	A2	DULA_SC_0p75MG_QW	52	arm, change	-1.420	0.080	275	registry:outcomes
NCT01191268	A3	INS_GLARGINE	52	arm, change	-1.230	0.080	276	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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