Network meta-analysis

HbA1c below 7 percent

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

weeks 20 to 36 (target week 26)Hypothetical (as if everyone stayed on treatment)Doses of a drug pooledOdds ratio

Randomized trials

Treatments

897

Participants

298

Events

In plain language

Across 2 trials with 897 participants, 1 of 2 treatments had a clearly better result than placebo on HbA1c below 7 percent, and for 1 the evidence could not tell it apart from placebo. The most favorable estimate was for Exenatide extended release injection: odds ratio 5.67 (95% credible interval 1.26 to 18.42).

Higher 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

Odds ratio. Higher values favor the treatment.

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
Treatment	Bayesian OR (95% CrI)	95% prediction interval	Frequentist OR (95% CI)	Verdict
Exenatide extended release injection EXENER_SC	5.67 (1.26 to 18.42)	0.69 to 34.21		Better
Lixisenatide injection LIXI_SC	2.00 (0.47 to 6.55)	0.27 to 11.56		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: odds ratio 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	EXENER_SC	LIXI_SC
PLACEBO	PLACEBO	0.18 0.05 to 0.79	0.50 0.15 to 2.12
EXENER_SC	5.67 1.26 to 18.42	EXENER_SC	2.84 0.45 to 17.81
LIXI_SC	2.00 0.47 to 6.55	0.35 0.06 to 2.24	LIXI_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.407 (95% CrI 0.096 to 1.642), log scale
Residual deviance: 4.0 for 4 data points
DIC: 7.9 (pD 4.0)
Largest R-hat: 1.003
Smallest ESS: bulk 3,194, tail 2,694
Divergent transitions: 0
Convergence: All criteria met
Priors: PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-1.77, 1.52^2) on tau^2 (Biological markers (dichotomised), 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.

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
NCT02229383 S000703	8.53	S2	11.3
GetGoal-Duo1 S000792	7.6	S2	9.15

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 7.6 (LIXI_SC vs PLACEBO) to 8.5 (EXENER_SC vs PLACEBO) percent; threshold 0.5
NoteOutcome assessment, time point: selected time points span 24 to 28 weeks

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
NCT02229383	28	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2014	adults; insulin glargine 20 U/d or more with or without metformin; HbA1c 7.0 to 10.5 percent at randomization
GetGoal-Duo1	24	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2009	T2D on metformin 1.5 g or more with or without SU, glinide or TZD, HbA1c 7 to 10, BMI over 20; HbA1c 7 to 9 after run in

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the odds ratio on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.

Trial data entering this analysis
Trial	Arm	Treatment	Week	Data	Events / N	Source
NCT02229383	A1	EXENER_SC	28	arm, responders	75 / 231	R0014763:Table 2
NCT02229383	A2	PLACEBO	28	arm, responders	17 / 230	R0014763:Table 2
GetGoal-Duo1	A1	PLACEBO	24	arm, responders	85 / 221	R0026107:Table 2
GetGoal-Duo1	A2	LIXI_SC	24	arm, responders	121 / 215	R0026107:Table 2

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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