Network 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)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean difference

Randomized trials

Treatments

897

Participants

Trial arms

In plain language

Across 3 trials with 897 participants, 1 of 3 treatments had a clearly better result than placebo on HbA1c change, and for 2 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 1.0 mg subcutaneous once weekly: mean difference -1.72 percentage points (95% credible interval -2.62 to -0.57).

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
Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW	-1.72 (-2.62 to -0.57)	-3.10 to -0.16	-1.75 (-2.00 to -1.50)	Better
Exenatide extended release 2 mg subcutaneous once weekly EXENER_SC_2MG_QW	-0.71 (-1.66 to 0.35)	-2.09 to 0.77	-0.73 (-0.95 to -0.51)	Unclear
Lixisenatide 20 ug subcutaneous once daily LIXI_SC_20UG_QD	-0.30 (-1.32 to 0.74)	-1.74 to 1.22	-0.30 (-0.58 to -0.02)	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	PLACEBO	SEMA_SC_1p0MG_QW	EXENER_SC_2MG_QW	LIXI_SC_20UG_QD
PLACEBO	PLACEBO	1.72 0.57 to 2.62	0.71 -0.35 to 1.66	0.30 -0.74 to 1.32
SEMA_SC_1p0MG_QW	-1.72 -2.62 to -0.57	SEMA_SC_1p0MG_QW	-1.00 -2.30 to 0.48	-1.42 -2.82 to 0.17
EXENER_SC_2MG_QW	-0.71 -1.66 to 0.35	1.00 -0.48 to 2.30	EXENER_SC_2MG_QW	-0.42 -1.84 to 1.11
LIXI_SC_20UG_QD	-0.30 -1.32 to 0.74	1.42 -0.17 to 2.82	0.42 -1.11 to 1.84	LIXI_SC_20UG_QD

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.324 (95% CrI 0.015 to 1.057)
Residual deviance: 5.0 for 5 data points
DIC: 10.1 (pD 5.0)
Largest R-hat: 1.002
Smallest ESS: bulk 2,481, tail 3,031
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; 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
NCT02229383 S000703	8.53	S2	11.3	1.3	57.7	28
GetGoal-Duo1 S000792	7.6	S2	9.15	19.5	56	24
SUSTAIN™ 5 S001872	8.37	S2	13.3	16.67	58.8	30

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_20UG_QD vs PLACEBO) to 8.5 (EXENER_SC_2MG_QW vs PLACEBO) percent; threshold 0.5
FlagBaseline, Diabetes duration: design means range from 9.1 (LIXI_SC_20UG_QD vs PLACEBO) to 13.3 (PLACEBO vs SEMA_SC_1p0MG_QW) years; threshold 3
FlagHeterogeneity, tau above threshold: tau 0.32 exceeds the outcome threshold 0.3; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 24 to 30 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 1, modified_itt 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
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
SUSTAIN™ 5	30	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2014	age 18 or older (20 in Japan); HbA1c 7.0 to 10.0 percent; stable basal insulin with or without metformin; eGFR 30 or more

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
NCT02229383	A1	EXENER_SC_2MG_QW	28	arm, change	-0.960	0.080	231	R0014763:Table 2
NCT02229383	A2	PLACEBO	28	arm, change	-0.230	0.080	230	R0014763:Table 2
GetGoal-Duo1	A1	PLACEBO	24	arm, change	-0.400	0.100	221	R0026107:Table 2
GetGoal-Duo1	A2	LIXI_SC_20UG_QD	24	arm, change	-0.700	0.100	215	R0026107:Table 2
SUSTAIN™ 5	A2	SEMA_SC_1p0MG_QW	30	contrast, md	-1.750	0.130		R0012671:Results
SUSTAIN™ 5	A3	PLACEBO	30	contrast, md				R0012671:Results

Rerun this analysis yourself

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