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)Hypothetical (as if everyone stayed on treatment)Doses of a drug pooledMean differenceSeparate part 2 of a disconnected network

Randomized trials

Treatments

1,393

Participants

Trial arms

In plain language

Across 2 trials with 1,393 participants, 0 of 3 treatments had a clearly better result than dapagliflozin on HbA1c change, and for 3 the evidence could not tell them apart from dapagliflozin. The most favorable estimate was for Exenatide extended release and dapagliflozin injection: mean difference -0.58 percentage points (95% credible interval -1.53 to 0.53).

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 Dapagliflozin

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

Versus Dapagliflozin. 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 Dapagliflozin
Treatment	Bayesian MD (95% CrI)	95% prediction interval	Frequentist MD (95% CI)	Verdict
Exenatide extended release and dapagliflozin injection DAPAEXEN_SC	-0.58 (-1.53 to 0.53)	-2.00 to 1.00	-0.59 (-0.85 to -0.33)	Unclear
Safiglipron (HRS-7535) tablet SAFIGL_PO	-0.30 (-1.31 to 0.72)	-1.80 to 1.17	-0.31 (-0.48 to -0.13)	Unclear
Exenatide extended release injection EXENER_SC	-0.20 (-1.21 to 0.92)	-1.69 to 1.37	-0.21 (-0.47 to 0.05)	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	DAPAGLIFLOZIN	DAPAEXEN_SC	SAFIGL_PO	EXENER_SC
DAPAGLIFLOZIN	DAPAGLIFLOZIN	0.58 -0.53 to 1.53	0.30 -0.72 to 1.31	0.20 -0.92 to 1.21
DAPAEXEN_SC	-0.58 -1.53 to 0.53	DAPAEXEN_SC	-0.28 -1.65 to 1.23	-0.38 -1.46 to 0.73
SAFIGL_PO	-0.30 -1.31 to 0.72	0.28 -1.23 to 1.65	SAFIGL_PO	-0.10 -1.62 to 1.39
EXENER_SC	-0.20 -1.21 to 0.92	0.38 -0.73 to 1.46	0.10 -1.39 to 1.62	EXENER_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.325 (95% CrI 0.017 to 1.086)
Residual deviance: 5.0 for 5 data points
DIC: 10.0 (pD 5.0)
Largest R-hat: 1.002
Smallest ESS: bulk 2,248, tail 2,675
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 -4.44089209850063e-16 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; 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	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
NCT06589765 S000558	8.6	S1	4.8 median	100 region: all sites in Asia	52.22	52
NCT02229396 S000791	9.3	S1	7.37	0.72	54.17	104

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 8.6 (DAPAGLIFLOZIN vs SAFIGL_PO) to 9.3 (DAPAEXEN_SC vs DAPAGLIFLOZIN vs EXENER_SC) percent; threshold 0.5
FlagBaseline, Asian ancestry or region: design means range from 0.7 (DAPAEXEN_SC vs DAPAGLIFLOZIN vs EXENER_SC) to 100.0 (DAPAGLIFLOZIN vs SAFIGL_PO) percent Asian; threshold 30
FlagBaseline, Treatment duration: design means range from 52.0 (DAPAGLIFLOZIN vs SAFIGL_PO) to 104.0 (DAPAEXEN_SC vs DAPAGLIFLOZIN vs EXENER_SC) weeks; threshold 26
FlagOutcome assessment, analysis set: confounded with design: modified_itt 1, randomized 1
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 28 to 32 weeks
NoteData handling, input conversions: arms_combined 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
NCT06589765	32	randomized	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2024	age 18 to 75; HbA1c 7.5 to 11.0 percent; BMI 19 to 40; metformin monotherapy; eGFR 45 or more
NCT02229396	28	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2014	age 18 or older; HbA1c 8.0 to 12.0 percent on metformin 1500 mg/d 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	Flags	Source
NCT06589765	A1+A2+A3	SAFIGL_PO	32	arm, change	-1.586	0.045	518	arms_combined	R0029347:Table 2
NCT06589765	A4	DAPAGLIFLOZIN	32	arm, change	-1.280	0.077	190		R0029347:Table 2
NCT02229396	A1	DAPAEXEN_SC	28	arm, change	-1.980	0.094	228		R0026313:Table 3
NCT02229396	A2	EXENER_SC	28	arm, change	-1.600	0.097	227		R0026313:Table 3
NCT02229396	A3	DAPAGLIFLOZIN	28	arm, change	-1.390	0.092	230		R0026313:Table 3

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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