Network meta-analysis

Systolic blood pressure change

Type 2 diabetes (adults)

weeks 20 to 36 (target week 26)Treatment policyDoses of a drug pooledMean difference

Randomized trials

Treatments

344

Participants

Trial arms

In plain language

Across 4 trials with 344 participants, 0 of 4 treatments had a clearly better result than placebo on systolic blood pressure change, and for 4 the evidence could not tell them apart from placebo. The most favorable estimate was for Sitagliptin: mean difference -2.88 mmHg (95% credible interval -18.10 to 13.03).

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 mmHg. 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
Sitagliptin SITAGLIPTIN	-2.88 (-18.10 to 13.03)	-21.82 to 16.46	-3.00 (-5.92 to -0.08)	Unclear
Semaglutide tablet SEMA_PO	-1.94 (-12.54 to 9.00)	-17.92 to 14.00	-2.00 (-4.50 to 0.50)	Unclear
Dulaglutide injection DULA_SC	-0.91 (-15.86 to 14.61)	-20.04 to 17.98	-1.00 (-5.30 to 3.30)	Unclear
Efsubaglutide alfa injection EFSUBA_SC	-0.41 (-11.92 to 10.54)	-17.15 to 16.17	-0.44 (-2.61 to 1.73)	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	SITAGLIPTIN	SEMA_PO	DULA_SC	EFSUBA_SC
PLACEBO	PLACEBO	2.88 -13.03 to 18.10	1.94 -9.00 to 12.54	0.91 -14.61 to 15.86	0.41 -10.54 to 11.92
SITAGLIPTIN	-2.88 -18.10 to 13.03	SITAGLIPTIN	-0.98 -12.20 to 10.58	-1.94 -17.47 to 14.49	-2.43 -21.26 to 17.88
SEMA_PO	-1.94 -12.54 to 9.00	0.98 -10.58 to 12.20	SEMA_PO	-0.98 -13.15 to 10.42	-1.49 -16.41 to 14.49
DULA_SC	-0.91 -15.86 to 14.61	1.94 -14.49 to 17.47	0.98 -10.42 to 13.15	DULA_SC	-0.48 -18.99 to 18.97
EFSUBA_SC	-0.41 -11.92 to 10.54	2.43 -17.88 to 21.26	1.49 -14.49 to 16.41	0.48 -18.97 to 18.99	EFSUBA_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 3.634 (95% CrI 0.183 to 12.383)
Residual deviance: 5.0 for 5 data points
DIC: 10.1 (pD 5.0)
Largest R-hat: 1.002
Smallest ESS: bulk 2,100, tail 2,998
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.

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; 4 of 4
PIONEER 4 S000133	32.94
PIONEER 10 S000234	26.26
PIONEER 12 S000522	28.58
NCT04998032 S002121	26.84

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 BMI or body weight: design means range from 26.3 (DULA_SC vs SEMA_PO) to 32.9 (PLACEBO vs SEMA_PO) kg/m2; threshold 3
FlagHeterogeneity, tau above threshold: tau 3.63 exceeds the outcome threshold 2; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 24 to 26 weeks
NoteOutcome assessment, analysis set: mixed: modified_itt 1, safety 3
NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 1, not stated 2, treatment_policy 1
NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 1, not stated 2, treatment_policy 1
NoteRisk of bias, blinding: mixed: double_blind 3, single_blind 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 4	26	safety	not stated	not stated	not stated	not stated	treatment_policy	treatment_policy	double_blind	industry	2016	Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more
PIONEER 10	26	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
PIONEER 12	26	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2019	adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent
NCT04998032	24	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2021	age 18 to 75; metformin monotherapy; HbA1c 7.5 to 10.5 at randomization; BMI 18.5 to 40; eGFR 60 or higher

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 4	A1	SEMA_PO	26	contrast, md	-2.000	1.276		R0015836:Supplement Table S9
PIONEER 4	A3	PLACEBO	26	contrast, md				R0015836:Supplement Table S9
PIONEER 10	A1	SEMA_PO	26	contrast, md	-1.000	1.786		R0018421:Supplement Table S4
PIONEER 10	A4	DULA_SC	26	contrast, md				R0018421:Supplement Table S4
PIONEER 12	A1	SEMA_PO	26	contrast, md	1.000	0.765		R0019776:ESM Table 5
PIONEER 12	A4	SITAGLIPTIN	26	contrast, md				R0019776:ESM Table 5
NCT04998032	A1	EFSUBA_SC	24	arm, change	-4.090	0.995	171	R0006975:Table 2
NCT04998032	A2	PLACEBO	24	arm, change	-3.650	0.490	173	R0006975:Table 2

Rerun this analysis yourself

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