LivingGLP1
Network meta-analysis

Systolic blood pressure change

Type 2 diabetes (adults)

weeks 20 to 36 (target week 26)While on treatmentEach dose separatelyMean difference
6
Randomized trials
8
Treatments
3,871
Participants
19
Trial arms

In plain language

Across 6 trials with 3,871 participants, 0 of 7 treatments had a clearly better result than placebo on systolic blood pressure change, and for 7 the evidence could not tell them apart from placebo. The most favorable estimate was for Liraglutide 1.8 mg subcutaneous once daily: mean difference -1.65 mmHg (95% credible interval -5.08 to 1.52).

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.
DULA_SC_0p75MG_QWINS_GLARGINELIRA_SC_1p8MG_QDPLACEBOSEMA_PO_14MG_QDSEMA_PO_3MG_QDSEMA_PO_7MG_QDSITAGLIPTIN
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.
-5-2.502.557.5← favors treatmentfavors reference →Liraglutide 1.8 mg subcutaneous …Semaglutide 14 mg oral once dail…Semaglutide 7 mg oral once daily…Dulaglutide 0.75 mg subcutaneous…SitagliptinSemaglutide 3 mg oral once daily…Insulin glargine
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
TreatmentBayesian MD (95% CrI)95% prediction intervalFrequentist MD (95% CI)Verdict
Liraglutide 1.8 mg subcutaneous once daily
LIRA_SC_1p8MG_QD
-1.65 (-5.08 to 1.52)-5.88 to 2.32-1.60 (-3.93 to 0.73)Unclear
Semaglutide 14 mg oral once daily (original tablet)
SEMA_PO_14MG_QD
-1.40 (-3.93 to 0.92)-4.92 to 1.99-1.40 (-3.31 to 0.51)Unclear
Semaglutide 7 mg oral once daily (original tablet)
SEMA_PO_7MG_QD
-0.13 (-2.92 to 2.59)-3.82 to 3.55-0.18 (-2.33 to 1.97)Unclear
Dulaglutide 0.75 mg subcutaneous once weekly
DULA_SC_0p75MG_QW
0.39 (-3.98 to 4.91)-4.61 to 5.420.35 (-3.40 to 4.09)Unclear
Sitagliptin
SITAGLIPTIN
0.49 (-2.62 to 3.77)-3.30 to 4.610.37 (-1.89 to 2.63)Unclear
Semaglutide 3 mg oral once daily (original tablet)
SEMA_PO_3MG_QD
0.92 (-1.76 to 3.80)-2.50 to 4.830.68 (-1.45 to 2.80)Unclear
Insulin glargine
INS_GLARGINE
2.70 (-2.69 to 8.26)-3.16 to 8.662.65 (-1.70 to 7.00)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 columnPLACEBOLIRA_SC_1p8MG_QDSEMA_PO_14MG_QDSEMA_PO_7MG_QDDULA_SC_0p75MG_QWSITAGLIPTINSEMA_PO_3MG_QDINS_GLARGINE
PLACEBOPLACEBO1.65
-1.52 to 5.08		1.40
-0.92 to 3.93		0.13
-2.59 to 2.92		-0.39
-4.91 to 3.98		-0.49
-3.77 to 2.62		-0.92
-3.80 to 1.76		-2.70
-8.26 to 2.69
LIRA_SC_1p8MG_QD-1.65
-5.08 to 1.52		LIRA_SC_1p8MG_QD-0.22
-3.32 to 2.81		-1.50
-5.06 to 1.95		-2.08
-7.07 to 2.73		-2.12
-6.06 to 1.47		-2.53
-6.26 to 0.76		-4.35
-10.37 to 1.29
SEMA_PO_14MG_QD-1.40
-3.93 to 0.92		0.22
-2.81 to 3.32		SEMA_PO_14MG_QD-1.29
-3.38 to 0.68		-1.81
-5.87 to 1.96		-1.88
-4.48 to 0.36		-2.32
-4.48 to -0.57		-4.11
-9.25 to 0.75
SEMA_PO_7MG_QD-0.13
-2.92 to 2.59		1.50
-1.95 to 5.06		1.29
-0.68 to 3.38		SEMA_PO_7MG_QD-0.53
-4.54 to 3.29		-0.61
-3.05 to 1.69		-1.04
-3.16 to 0.84		-2.84
-7.79 to 2.23
DULA_SC_0p75MG_QW0.39
-3.98 to 4.91		2.08
-2.73 to 7.07		1.81
-1.96 to 5.87		0.53
-3.29 to 4.54		DULA_SC_0p75MG_QW-0.10
-4.35 to 4.19		-0.51
-4.52 to 3.41		-2.30
-5.50 to 1.10
SITAGLIPTIN0.49
-2.62 to 3.77		2.12
-1.47 to 6.06		1.88
-0.36 to 4.48		0.61
-1.69 to 3.05		0.10
-4.19 to 4.35		SITAGLIPTIN-0.41
-2.45 to 1.50		-2.21
-7.38 to 3.05
SEMA_PO_3MG_QD0.92
-1.76 to 3.80		2.53
-0.76 to 6.26		2.32
0.57 to 4.48		1.04
-0.84 to 3.16		0.51
-3.41 to 4.52		0.41
-1.50 to 2.45		SEMA_PO_3MG_QD-1.78
-6.71 to 3.38
INS_GLARGINE2.70
-2.69 to 8.26		4.35
-1.29 to 10.37		4.11
-0.75 to 9.25		2.84
-2.23 to 7.79		2.30
-1.10 to 5.50		2.21
-3.05 to 7.38		1.78
-3.38 to 6.71		INS_GLARGINE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.783 (95% CrI 0.040 to 2.826)
Residual deviance
17.1 for 18 data points
DIC
31.4 (pD 14.2)
Largest R-hat
1.003
Smallest ESS
bulk 1,945, tail 2,869
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
I squared
1%
Q (total)
6.09 on 6 df, P = 0.413
Q (between designs)
6.09, P = 0.413

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
TrialBaseline BMI or body weight (kg/m2)
effect modifier, prognostic factor; 5 of 6
PIONEER 4
S000133
32.94
PIONEER 10
S000234
26.26
NCT01584232
S000246
26
PIONEER 12
S000522
28.58
PIONEER 11
S001791
28.2
PIONEER 3
S002267
not reported

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 26.0 (DULA_SC_0p75MG_QW vs INS_GLARGINE) to 32.9 (LIRA_SC_1p8MG_QD vs PLACEBO vs SEMA_PO_14MG_QD) kg/m2; threshold 3
  • NoteOutcome assessment, analysis set: mixed: full_analysis 4, safety 2
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 2, not stated 3, treatment_policy 1
  • NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 2, not stated 3, treatment_policy 1
  • NoteRisk of bias, blinding: mixed: double_blind 4, open_label 1, single_blind 1
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
PIONEER 426full_analysisnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2016Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more
PIONEER 1026full_analysisnot statednot statednot statednot statedtreatment_policytreatment_policysingle_blindindustry2017Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
NCT0158423226safetynot statednot statednot statednot statednot statednot statedopen_labelindustry2012Japanese adults 20 years or older; BMI 18.5 to less than 35 kg/m2; HbA1c 7.0 to 10.0 percent; on sulfonylurea and/or biguanide
PIONEER 1226safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2019adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent
PIONEER 1126full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2019age 18 or older; HbA1c 7.0 to 10.0 percent at screening, 7.0 to 9.5 at randomization; no glucose lowering drugs; eGFR 60 or more
PIONEER 326full_analysisnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2016adults 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
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
PIONEER 4A1SEMA_PO_14MG_QD26arm, change-4.0000.770285registry:outcomes
PIONEER 4A2LIRA_SC_1p8MG_QD26arm, change-4.0000.771284registry:outcomes
PIONEER 4A3PLACEBO26arm, change-2.0001.091142registry:outcomes
PIONEER 10A1SEMA_PO_3MG_QD26arm, change-3.0001.136131registry:outcomes
PIONEER 10A2SEMA_PO_7MG_QD26arm, change-5.0001.132132registry:outcomes
PIONEER 10A3SEMA_PO_14MG_QD26arm, change-6.0001.316130registry:outcomes
PIONEER 10A4DULA_SC_0p75MG_QW26arm, change-4.0001.48865registry:outcomes
NCT01584232A1DULA_SC_0p75MG_QW26arm, change0.4000.800181R0016159:Table 3
NCT01584232A2INS_GLARGINE26arm, change2.7000.800180R0016159:Table 3
PIONEER 12A1SEMA_PO_3MG_QD26contrast, md0.0000.765R0019776:ESM Table 5
PIONEER 12A4SITAGLIPTIN26contrast, mdR0019776:ESM Table 5
PIONEER 11A1SEMA_PO_3MG_QD26arm, change1.0001.182121registry:outcomes
PIONEER 11A2SEMA_PO_7MG_QD26arm, change-2.0001.086122registry:outcomes
PIONEER 11A3SEMA_PO_14MG_QD26arm, change-4.0001.207116registry:outcomes
PIONEER 11A4PLACEBO26arm, change-2.0001.182121registry:outcomes
PIONEER 3A1SEMA_PO_3MG_QD26arm, change-2.0000.649466registry:outcomes
PIONEER 3A2SEMA_PO_7MG_QD26arm, change-2.0000.696464registry:outcomes
PIONEER 3A3SEMA_PO_14MG_QD26arm, change-3.0000.649465registry:outcomes
PIONEER 3A4SITAGLIPTIN26arm, change-2.0000.695466registry:outcomes

Rerun this analysis yourself

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