Network meta-analysis

Systolic blood pressure change

Type 2 diabetes (adults)

weeks 64 to 130 (target week 104)Not stated by the trialsEach dose separatelyMean difference

Randomized trials

Treatments

8,384

Participants

Trial arms

In plain language

Across 3 trials with 8,384 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 Semaglutide 14 mg oral once daily (original tablet): mean difference -2.97 mmHg (95% credible interval -14.49 to 9.17).

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
Semaglutide 14 mg oral once daily (original tablet) SEMA_PO_14MG_QD	-2.97 (-14.49 to 9.17)	-19.52 to 14.29	-3.00 (-4.34 to -1.66)	Unclear
Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW	-2.88 (-14.39 to 8.86)	-19.64 to 14.29	-2.89 (-4.19 to -1.60)	Unclear
Semaglutide 0.5 mg subcutaneous once weekly SEMA_SC_0p5MG_QW	-0.92 (-12.17 to 10.48)	-17.27 to 15.56	-0.96 (-2.26 to 0.33)	Unclear
Albiglutide flexible dose injection once weekly ALBI_SC_FLEX_30-50_QW	-0.35 (-12.61 to 11.14)	-17.55 to 16.45	-0.30 (-1.77 to 1.17)	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	SEMA_PO_14MG_QD	SEMA_SC_1p0MG_QW	SEMA_SC_0p5MG_QW	ALBI_SC_FLEX_30-50_QW
PLACEBO	PLACEBO	2.97 -9.17 to 14.49	2.88 -8.86 to 14.39	0.92 -10.48 to 12.17	0.35 -11.14 to 12.61
SEMA_PO_14MG_QD	-2.97 -14.49 to 9.17	SEMA_PO_14MG_QD	-0.14 -17.18 to 17.04	-1.98 -18.10 to 14.51	-2.68 -19.30 to 15.32
SEMA_SC_1p0MG_QW	-2.88 -14.39 to 8.86	0.14 -17.04 to 17.18	SEMA_SC_1p0MG_QW	-1.94 -13.71 to 9.93	-2.51 -18.37 to 14.44
SEMA_SC_0p5MG_QW	-0.92 -12.17 to 10.48	1.98 -14.51 to 18.10	1.94 -9.93 to 13.71	SEMA_SC_0p5MG_QW	-0.57 -16.32 to 16.41
ALBI_SC_FLEX_30-50_QW	-0.35 -12.61 to 11.14	2.68 -15.32 to 19.30	2.51 -14.44 to 18.37	0.57 -16.41 to 16.32	ALBI_SC_FLEX_30-50_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 3.842 (95% CrI 0.184 to 12.490)
Residual deviance: 7.0 for 7 data points
DIC: 14.1 (pD 7.0)
Largest R-hat: 1.004
Smallest ESS: bulk 1,807, tail 2,620
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 -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 BMI or body weight (kg/m2) effect modifier, prognostic factor; 3 of 3
NCT02465515 S001074	32.3
PIONEER 6 S001381	32.3
SUSTAIN™ 6 S001933	32.8

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: full_analysis 1, other 1, safety 1
FlagHeterogeneity, tau above threshold: tau 3.84 exceeds the outcome threshold 2; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 83 to 104.28 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
NCT02465515	104.28	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2015	type 2 diabetes with established cardiovascular disease
PIONEER 6	83	other	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2017	T2D; age 50 or more with CVD or CKD, or 60 or more with CV risk factors
SUSTAIN™ 6	104	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2013	T2D HbA1c 7.0 or more; age 50 or more with CVD, CHF or CKD stage 3 or more, or age 60 or more with CV risk factor

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
NCT02465515	A1	PLACEBO	104.28	arm, change	-0.900	0.553	1,133		registry:outcomes
NCT02465515	A2	ALBI_SC_FLEX_30-50_QW	104.28	arm, change	-1.200	0.506	1,198		registry:outcomes
PIONEER 6	A1	SEMA_PO_14MG_QD	83	arm, change	-5.000	0.491	1,345		registry:outcomes
PIONEER 6	A2	PLACEBO	83	arm, change	-2.000	0.479	1,411		registry:outcomes
SUSTAIN™ 6	A1	SEMA_SC_0p5MG_QW	104	arm, change	-3.440	0.540	826		registry:outcomes
SUSTAIN™ 6	A2	SEMA_SC_1p0MG_QW	104	arm, change	-5.370	0.540	822		registry:outcomes
SUSTAIN™ 6	A3+A4	PLACEBO	104	arm, change	-2.475	0.382	1,649	arms_combined	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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