Network meta-analysis

HbA1c change

Type 2 diabetes (adults); background therapy: no glucose lowering drug (lifestyle only)

weeks 36 to 64 (target week 52)Not stated by the trialsDoses of a drug pooledMean differenceSeparate part 2 of a disconnected network

Randomized trials

Treatments

281

Participants

Trial arms

In plain language

Across 2 trials with 281 participants, 0 of 3 treatments had a clearly better result than standard care or no added treatment on HbA1c change, and for 3 the evidence could not tell them apart from standard care or no added treatment. The most favorable estimate was for Exenatide injection: mean difference -0.09 percentage points (95% credible interval -1.11 to 0.77).

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 Standard care or no added treatment

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

Versus Standard care or no added treatment. 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 Standard care or no added treatment
Treatment	Bayesian MD (95% CrI)	95% prediction interval	Frequentist MD (95% CI)	Verdict
Exenatide injection EXEN_SC	-0.09 (-1.11 to 0.77)	-1.50 to 1.25	-0.08 (-0.50 to 0.34)	Unclear
Premixed insulin INS_PREMIX	0.20 (-1.16 to 1.36)	-1.50 to 1.72	0.22 (-0.21 to 0.65)	Unclear
Pioglitazone PIOGLITAZONE	0.21 (-1.10 to 1.39)	-1.45 to 1.72	0.22 (-0.21 to 0.65)	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	STANDARD_CARE	EXEN_SC	INS_PREMIX	PIOGLITAZONE
STANDARD_CARE	STANDARD_CARE	0.09 -0.77 to 1.11	-0.20 -1.36 to 1.16	-0.21 -1.39 to 1.10
EXEN_SC	-0.09 -1.11 to 0.77	EXEN_SC	-0.29 -1.22 to 0.69	-0.30 -1.27 to 0.70
INS_PREMIX	0.20 -1.16 to 1.36	0.29 -0.69 to 1.22	INS_PREMIX	-0.00 -0.99 to 0.96
PIOGLITAZONE	0.21 -1.10 to 1.39	0.30 -0.70 to 1.27	0.00 -0.96 to 0.99	PIOGLITAZONE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.312 (95% CrI 0.016 to 1.050)
Residual deviance: 4.9 for 5 data points
DIC: 9.9 (pD 4.9)
Largest R-hat: 1.003
Smallest ESS: bulk 2,577, tail 2,817
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; 1 of 2	Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 2 of 2	Diabetes duration (years) effect modifier, prognostic factor; 0 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
NCT01147627 S000864	not reported	S0	not reported	100 region: all sites in Asia	50.31	48
NCT01776788 S002224	10.05	S0	not reported	100 region: all sites in Asia	45	12

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: not reported by 1 of 2 trials
FlagBaseline, Diabetes duration: not reported by 2 of 2 trials
FlagBaseline, Treatment duration: design means range from 12.0 (EXEN_SC vs STANDARD_CARE) to 48.0 (EXEN_SC vs INS_PREMIX vs PIOGLITAZONE) weeks; threshold 26
FlagOutcome assessment, analysis set: confounded with design: completers 1, other 1
FlagOutcome assessment, definition: confounded with design: HbA1c adjusted for baseline by ANCOVA, participants still in remission 1, not stated 1
FlagRisk of bias, funding: confounded with design: industry 1, mixed 1
FlagHeterogeneity, tau above threshold: tau 0.31 exceeds the outcome threshold 0.3; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 48 to 52.18 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
NCT01147627	48	completers	not stated	not stated	not stated	not stated	not stated	not stated	open_label	mixed	2010	newly diagnosed drug naive T2D; age 30 to 70; HbA1c 7 to 10 percent; BMI 20 to 35
NCT01776788	52.18	other	HbA1c adjusted for baseline by ANCOVA, participants still in remission	not stated	not stated	not stated	not stated	not stated	open_label	industry	2012	age 30 to 70; newly diagnosed drug naive; FPG 7.0 to 16.7 mmol/L; BMI 20 to 35

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
NCT01147627	A1	EXEN_SC	48	arm, change	-1.900	0.021	88	R0021706:Table 1
NCT01147627	A2	INS_PREMIX	48	arm, change	-1.600	0.033	84	R0021706:Table 1
NCT01147627	A3	PIOGLITAZONE	48	arm, change	-1.600	0.019	109	R0021706:Table 1
NCT01776788	A1	STANDARD_CARE	52.18	arm, final	6.250	0.176		R0024844:Table 1
NCT01776788	A2	EXEN_SC	52.18	arm, final	6.170	0.125		R0024844:Table 1

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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