Network meta-analysis

SF-36 physical component summary change

Type 2 diabetes (adults)

weeks 20 to 130 (target week 52)Treatment policyDoses of a drug pooledMean difference

Randomized trials

Treatments

1,863

Participants

Trial arms

In plain language

Across 2 trials with 1,863 participants, 0 of 2 treatments had a clearly better result than semaglutide tablet on SF-36 physical component summary change, and for 2 the evidence could not tell them apart from semaglutide tablet. The most favorable estimate was for Dulaglutide injection: mean difference 0.54 points (95% credible interval -6.53 to 8.44).

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 Semaglutide tablet

Mean difference in points. Higher values favor the treatment.

Versus Semaglutide tablet. 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 Semaglutide tablet
Treatment	Bayesian MD (95% CrI)	95% prediction interval	Frequentist MD (95% CI)	Verdict
Dulaglutide injection DULA_SC	0.54 (-6.53 to 8.44)	-10.49 to 12.13	0.55 (-0.77 to 1.86)	Unclear
Sitagliptin SITAGLIPTIN	0.04 (-7.74 to 7.94)	-11.25 to 11.59	0.06 (-0.63 to 0.74)	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	SEMA_PO	DULA_SC	SITAGLIPTIN
SEMA_PO	SEMA_PO	-0.54 -8.44 to 6.53	-0.04 -7.94 to 7.74
DULA_SC	0.54 -6.53 to 8.44	DULA_SC	0.48 -10.03 to 11.89
SITAGLIPTIN	0.04 -7.74 to 7.94	-0.48 -11.89 to 10.03	SITAGLIPTIN

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 2.504 (95% CrI 0.091 to 8.593)
Residual deviance: 3.0 for 3 data points
DIC: 6.1 (pD 3.0)
Largest R-hat: 1.001
Smallest ESS: bulk 2,330, tail 2,108
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 40^2); PR03 N(0, 20^2); PR07 half normal(0, 4^2) 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.

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.

FlagOutcome assessment, instrument: confounded with design: not stated 1, SF-36v2 1
FlagRisk of bias, blinding: confounded with design: double_blind 1, single_blind 1
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
PIONEER 10	52	full_analysis	not stated	SF-36v2	not stated	not stated	treatment_policy	treatment_policy	single_blind	industry	2017	Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
PIONEER 3	52	full_analysis	not stated	not stated	not stated	not stated	treatment_policy	treatment_policy	double_blind	industry	2016	adults with T2D; HbA1c 7.0 to 10.5 percent; metformin with or without sulfonylurea

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
PIONEER 10	A1	SEMA_PO	52	contrast, md	-0.550	0.671			R0018421:Supplement Figure S5A
PIONEER 10	A4	DULA_SC	52	contrast, md					R0018421:Supplement Figure S5A
PIONEER 3	A1+A2+A3	SEMA_PO	52	arm, change	0.253	0.177	1,396	arms_combined	registry:outcomes
PIONEER 3	A4	SITAGLIPTIN	52	arm, change	0.310	0.303	467		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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