Network meta-analysis

HbA1c change

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

weeks 20 to 36 (target week 26)While on treatmentEach dose separatelyMean difference

Randomized trials

Treatments

2,239

Participants

Trial arms

In plain language

Across 4 trials with 2,239 participants, 1 of 2 treatments had a clearly better result than placebo on HbA1c change, and for 1 the evidence could not tell it apart from placebo. The most favorable estimate was for Exenatide 10 ug subcutaneous twice daily: mean difference -0.74 percentage points (95% credible interval -1.46 to 0.10).

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

Mean difference in percentage points. Lower 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
Exenatide 10 ug subcutaneous twice daily EXEN_SC_10UG_BID	-0.74 (-1.46 to 0.10)	-1.73 to 0.31	-0.75 (-1.15 to -0.34)	Unclear
Lixisenatide 20 ug subcutaneous once daily LIXI_SC_20UG_QD	-0.58 (-0.96 to -0.14)	-1.39 to 0.29	-0.58 (-0.80 to -0.35)	Better

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	EXEN_SC_10UG_BID	LIXI_SC_20UG_QD
PLACEBO	PLACEBO	0.74 -0.10 to 1.46	0.58 0.14 to 0.96
EXEN_SC_10UG_BID	-0.74 -1.46 to 0.10	EXEN_SC_10UG_BID	-0.16 -0.83 to 0.56
LIXI_SC_20UG_QD	-0.58 -0.96 to -0.14	0.16 -0.56 to 0.83	LIXI_SC_20UG_QD

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.218 (95% CrI 0.021 to 0.772)
Residual deviance: 8.1 for 8 data points
DIC: 15.8 (pD 7.6)
Largest R-hat: 1.002
Smallest ESS: bulk 1,924, tail 2,520
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: 0.156
I squared: 62%
Q (total): 5.31 on 2 df, P = 0.070
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; 4 of 4	Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 4 of 4	Diabetes duration (years) effect modifier, prognostic factor; 3 of 4	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 4 of 4	Age (years) prognostic factor; 4 of 4	Treatment duration (weeks) effect modifier; 4 of 4
GETGOAL-S S000491	8.26	S1	not reported	44.82	57.27	24
GetGoal-M-Asia S001185	7.9	S1	6.64	99.74	54.8	24
GETGOAL-P S001204	8.07	S1	8.1	4.55	55.77	24
GETGOAL-X S001439	7.96	S1	6.77	1.1	57.45	24

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, Diabetes duration: not reported by 1 of 4 trials
FlagBaseline, Asian ancestry or region: design means range from 1.1 (EXEN_SC_10UG_BID vs LIXI_SC_20UG_QD) to 49.7 (LIXI_SC_20UG_QD vs PLACEBO) percent Asian; threshold 30
FlagRisk of bias, blinding: confounded with design: double_blind 3, open_label 1
NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 3, while_on_treatment 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
GETGOAL-S	24	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2008	adults on sulfonylurea with or without metformin; HbA1c 7 to 10 percent
GetGoal-M-Asia	24	modified_itt	not stated	not stated	not stated	not stated	while_on_treatment	not stated	double_blind	industry	2010	Asian adults with type 2 diabetes on metformin with or without sulfonylurea
GETGOAL-P	24	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2008	type 2 diabetes on pioglitazone 30 mg or more with or without metformin; HbA1c 7 percent or more
GETGOAL-X	24	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	open_label	industry	2008	age 21 to 84; HbA1c 7 to 10 percent; metformin at least 1.5 g/day

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
GETGOAL-S	A1	PLACEBO	24	arm, change	-0.100	0.071	274	registry:outcomes
GETGOAL-S	A2	LIXI_SC_20UG_QD	24	arm, change	-0.850	0.061	544	registry:outcomes
GetGoal-M-Asia	A1	PLACEBO	24	arm, change	-0.470	0.104	188	registry:outcomes
GetGoal-M-Asia	A2	LIXI_SC_20UG_QD	24	arm, change	-0.830	0.102	185	registry:outcomes
GETGOAL-P	A1	PLACEBO	24	arm, change	-0.340	0.100	148	registry:outcomes
GETGOAL-P	A2	LIXI_SC_20UG_QD	24	arm, change	-0.900	0.089	308	registry:outcomes
GETGOAL-X	A1	LIXI_SC_20UG_QD	24	arm, change	-0.790	0.050	295	R0022279:Results
GETGOAL-X	A2	EXEN_SC_10UG_BID	24	arm, change	-0.960	0.050	297	R0022279:Results

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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