Pairwise meta-analysis

HbA1c change

Type 2 diabetes (adults); background therapy: basal insulin with or without non insulin drugs

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

Randomized trials

Treatments

1,208

Participants

Trial arms

In plain language

Across 3 trials with 1,208 participants, 1 of 1 treatment had a clearly better result than placebo on HbA1c change. The most favorable estimate was for Lixisenatide 20 ug subcutaneous once daily: mean difference -0.55 percentage points (95% credible interval -1.04 to -0.09).

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
Lixisenatide 20 ug subcutaneous once daily LIXI_SC_20UG_QD	-0.55 (-1.04 to -0.09)	-1.45 to 0.37	-0.56 (-0.83 to -0.28)	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.

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.251 (95% CrI 0.019 to 0.831)
Residual deviance: 6.4 for 6 data points
DIC: 12.0 (pD 5.6)
Largest R-hat: 1.001
Smallest ESS: bulk 2,129, tail 2,389
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: 0.189
I squared: 59%
Q (total): 4.91 on 2 df, P = 0.086

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; 3 of 3	Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 3 of 3	Diabetes duration (years) effect modifier, prognostic factor; 3 of 3	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 3 of 3	Age (years) prognostic factor; 3 of 3	Treatment duration (weeks) effect modifier; 3 of 3
GETGOAL-L-ASIA S000488	8.53	S2	13.9	100	58.35	24
NCT01632163 S001963	7.9	S2	10.25	85.95	55.05	24
GETGOAL-L S002023	8.4	S2	12.46	16.73	57.23	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.

NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 1, while_on_treatment 2

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-L-ASIA	24	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2009	age 25 to 81; type 2 diabetes at least 1 year; stable basal insulin at least 10 U/day with or without sulfonylurea; HbA1c 7 to 10 percent
NCT01632163	24	modified_itt	not stated	not stated	not stated	not stated	while_on_treatment	not stated	double_blind	industry	2012	adults; T2D at least 1 year; HbA1c 7 to 10.5 at screening, 7 to 9.5 after run in; basal insulin at least 15 U
GETGOAL-L	24	modified_itt	not stated	not stated	not stated	not stated	while_on_treatment	not stated	double_blind	industry	2008	adults; HbA1c 7.0 to 10.0 percent; stable basal 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
GETGOAL-L-ASIA	A1	LIXI_SC_20UG_QD	24	arm, change	-0.770	0.137	146	registry:outcomes
GETGOAL-L-ASIA	A2	PLACEBO	24	arm, change	0.110	0.131	154	registry:outcomes
NCT01632163	A1	LIXI_SC_20UG_QD	24	arm, change	-0.620	0.090	223	R0014725:Results
NCT01632163	A2	PLACEBO	24	arm, change	-0.110	0.090	223	R0014725:Results
GETGOAL-L	A1	PLACEBO	24	arm, change	-0.380	0.107	158	registry:outcomes
GETGOAL-L	A2	LIXI_SC_20UG_QD	24	arm, change	-0.740	0.090	304	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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