Network meta-analysis

Systolic blood pressure change

Type 2 diabetes (adults)

weeks 36 to 64 (target week 52)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean differenceSeparate part 2 of a disconnected network

Randomized trials

Treatments

416

Participants

Trial arms

In plain language

Across 2 trials with 416 participants, 0 of 2 treatments had a clearly better result than dulaglutide 0.75 mg subcutaneous once weekly on systolic blood pressure change, and for 2 the evidence could not tell them apart from dulaglutide 0.75 mg subcutaneous once weekly. The most favorable estimate was for liraglutide 0.9 mg injection once daily: mean difference -3.09 mmHg (95% credible interval -15.26 to 9.47).

Liraglutide 0.9 mg injection once daily: not convincingly different from dulaglutide 0.75 mg subcutaneous once weekly (certainty pending).
Semaglutide 3 mg oral once daily (original tablet): not convincingly different from dulaglutide 0.75 mg subcutaneous once weekly (certainty pending).

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 Dulaglutide 0.75 mg subcutaneous once weekly

Mean difference in mmHg. Lower values favor the treatment.

Versus Dulaglutide 0.75 mg subcutaneous once weekly. 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 Dulaglutide 0.75 mg subcutaneous once weekly
Treatment	Bayesian MD (95% CrI)	95% prediction interval	Frequentist MD (95% CI)	Verdict	Confidence
Liraglutide 0.9 mg injection once daily LIRA_SC_0p9MG_QD	-3.09 (-15.26 to 9.47)	-20.68 to 14.80	-3.18 (-5.45 to -0.91)	Unclear	pending
Semaglutide 3 mg oral once daily (original tablet) SEMA_PO_3MG_QD	-0.99 (-13.17 to 12.23)	-18.48 to 17.26	-1.00 (-4.50 to 2.50)	Unclear	pending

Confidence in the results

How much each comparison can be trusted, rated with CINeMA in six domains and summarized with GRADE.

Ratings follow the protocol's numeric rules from risk of bias and indirectness judgments made by language model reviewers (amendment A028); no human has verified them yet. Reporting bias (ROB-MEN): some concerns.

Confidence in each comparison with Dulaglutide 0.75 mg subcutaneous once weekly
Comparison	Within study bias	Reporting bias	Indirectness	Imprecision	Heterogeneity	Incoherence	Confidence
Liraglutide 0.9 mg injection once daily versus Dulaglutide 0.75 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Semaglutide 3 mg oral once daily (original tablet) versus Dulaglutide 0.75 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending

Every other comparison (1)

Confidence in the other comparisons
Comparison	Within study bias	Reporting bias	Indirectness	Imprecision	Heterogeneity	Incoherence	Confidence
Liraglutide 0.9 mg injection once daily versus Semaglutide 3 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending

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.

Rank probabilities

Probability of each rank for each treatment
Treatment	Rank 1	Rank 2	Rank 3	Mean rank
LIRA_SC_0p9MG_QD	61%	23%	16%	1.6
SEMA_PO_3MG_QD	30%	34%	36%	2.1
DULA_SC_0p75MG_QW	9%	43%	48%	2.4

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	DULA_SC_0p75MG_QW	LIRA_SC_0p9MG_QD	SEMA_PO_3MG_QD
DULA_SC_0p75MG_QW	DULA_SC_0p75MG_QW	3.09 -9.47 to 15.26	0.99 -12.23 to 13.17
LIRA_SC_0p9MG_QD	-3.09 -15.26 to 9.47	LIRA_SC_0p9MG_QD	-2.04 -19.89 to 14.44
SEMA_PO_3MG_QD	-0.99 -13.17 to 12.23	2.04 -14.44 to 19.89	SEMA_PO_3MG_QD

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 3.978 (95% CrI 0.180 to 13.383)
Residual deviance: 3.0 for 3 data points
DIC: 6.0 (pD 3.0)
Largest R-hat: 1.004
Smallest ESS: bulk 1,962, tail 2,041
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 60^2); PR03 N(0, 30^2); PR07 half normal(0, 6^2) 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.

Contribution of direct evidence

Percent contribution of each direct comparison (columns) to each network estimate (rows), from netcontrib.

Contribution of direct comparisons to network estimates
Network estimate	DULA_SC_0p75MG_QW:LIRA_SC_0p9MG_QD	DULA_SC_0p75MG_QW:SEMA_PO_3MG_QD
DULA_SC_0p75MG_QW:LIRA_SC_0p9MG_QD	100
DULA_SC_0p75MG_QW:SEMA_PO_3MG_QD		100

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 BMI or body weight (kg/m2) effect modifier, prognostic factor; 2 of 2
PIONEER 10 S000234	26.26
NCT01558271 S000837	25.51

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, analysis set: confounded with design: modified_itt 1, safety 1
FlagOutcome assessment, intercurrent events (discontinuation): confounded with design: hypothetical 1, not stated 1
FlagOutcome assessment, intercurrent events (rescue): confounded with design: hypothetical 1, not stated 1
FlagRisk of bias, blinding: confounded with design: double_blind 1, single_blind 1
FlagHeterogeneity, tau above threshold: tau 3.98 exceeds the outcome threshold 2; the flags of this network are candidate explanations

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	safety	not stated	not stated	not stated	not stated	hypothetical	hypothetical	single_blind	industry	2017	Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
NCT01558271	52	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2012	Japanese; age 20 or more; BMI 18.5 to 35; HbA1c 7.0 to 10.0 percent; OAM naive or OAM stopped

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
PIONEER 10	A1	SEMA_PO_3MG_QD	52	contrast, md	-1.000	1.786		R0018421:Supplement Table S4
PIONEER 10	A4	DULA_SC_0p75MG_QW	52	contrast, md				R0018421:Supplement Table S4
NCT01558271	A1	DULA_SC_0p75MG_QW	52	arm, change	1.320	0.660	280	registry:outcomes
NCT01558271	A2	LIRA_SC_0p9MG_QD	52	arm, change	-1.860	0.950	136	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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