Network meta-analysis

Systolic blood pressure change

Type 2 diabetes (adults)

weeks 36 to 64 (target week 52)Treatment policyEach dose separatelyMean differenceSeparate part 3 of a disconnected network

Randomized trials

Treatments

Participants

Trial arms

In plain language

Across 4 trials, 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 Tirzepatide 5 mg subcutaneous once weekly: mean difference -4.36 mmHg (95% credible interval -15.77 to 8.49).

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
Tirzepatide 5 mg subcutaneous once weekly TIRZ_SC_5MG_QW	-4.36 (-15.77 to 8.49)	-21.74 to 12.97	-4.40 (-7.80 to -1.00)	Unclear
Liraglutide 3.0 mg subcutaneous once daily LIRA_SC_3p0MG_QD	-3.96 (-15.35 to 8.32)	-20.63 to 13.94	-4.00 (-6.45 to -1.55)	Unclear
Semaglutide 2.4 mg subcutaneous once weekly SEMA_SC_2p4MG_QW	-2.38 (-14.32 to 9.61)	-19.90 to 14.64	-2.50 (-5.30 to 0.30)	Unclear
Insulin degludec INS_DEGLUDEC	0.60 (-14.76 to 17.82)	-19.18 to 21.26	0.50 (-3.39 to 4.39)	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	TIRZ_SC_5MG_QW	LIRA_SC_3p0MG_QD	SEMA_SC_2p4MG_QW	INS_DEGLUDEC
PLACEBO	PLACEBO	4.36 -8.49 to 15.77	3.96 -8.32 to 15.35	2.38 -9.61 to 14.32	-0.60 -17.82 to 14.76
TIRZ_SC_5MG_QW	-4.36 -15.77 to 8.49	TIRZ_SC_5MG_QW	-0.39 -17.58 to 16.00	-1.93 -18.80 to 15.57	-4.93 -16.96 to 6.88
LIRA_SC_3p0MG_QD	-3.96 -15.35 to 8.32	0.39 -16.00 to 17.58	LIRA_SC_3p0MG_QD	-1.57 -17.64 to 15.46	-4.63 -24.37 to 15.28
SEMA_SC_2p4MG_QW	-2.38 -14.32 to 9.61	1.93 -15.57 to 18.80	1.57 -15.46 to 17.64	SEMA_SC_2p4MG_QW	-3.08 -24.03 to 16.86
INS_DEGLUDEC	0.60 -14.76 to 17.82	4.93 -6.88 to 16.96	4.63 -15.28 to 24.37	3.08 -16.86 to 24.03	INS_DEGLUDEC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 3.872 (95% CrI 0.172 to 12.566)
Residual deviance: 4.0 for 4 data points
DIC: 7.9 (pD 4.0)
Largest R-hat: 1.002
Smallest ESS: bulk 1,923, tail 2,544
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
SCALE™ Insulin S000159	35.6
STEP HFpEF DM S000161	36.9 median
SURPASS-3 S001591	33.5
SURPASS-5 S001608	33.4

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 33.4 (PLACEBO vs TIRZ_SC_5MG_QW) to 36.9 (PLACEBO vs SEMA_SC_2p4MG_QW) kg/m2; threshold 3
FlagHeterogeneity, tau above threshold: tau 3.87 exceeds the outcome threshold 2; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 40 to 56 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 2, safety 2
NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 1, treatment_policy 3
NoteOutcome assessment, intercurrent events (rescue): mixed: not stated 3, treatment_policy 1
NoteRisk of bias, blinding: mixed: double_blind 3, open_label 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
SCALE™ Insulin	56	full_analysis	not stated	not stated	not stated	not stated	treatment_policy	not stated	double_blind	industry	2017	age 18 or older; BMI 27 or higher; HbA1c 6.0 to 10 percent; basal insulin plus up to 2 oral drugs
STEP HFpEF DM	52	full_analysis	not stated	not stated	not stated	not stated	treatment_policy	treatment_policy	double_blind	industry	2021	age 18 or older; heart failure with LVEF 45% or more; BMI 30 or more; type 2 diabetes with HbA1c 10% or less
SURPASS-3	40	safety	not stated	not stated	not stated	not stated	not stated	not stated	open_label	industry	2019	insulin naive; HbA1c 7.0 to 10.5 percent; BMI at least 25; metformin with or without SGLT2i; eGFR above 45
SURPASS-5	40	safety	not stated	not stated	not stated	not stated	treatment_policy	not stated	double_blind	industry	2019	HbA1c 7.0 to 10.5 percent; BMI 23 or higher; insulin glargine above 0.25 U/kg or 20 U daily with or without metformin

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	Source
SCALE™ Insulin	A1	LIRA_SC_3p0MG_QD	56	contrast, md	-4.000	1.250	R0024063:Table 2
SCALE™ Insulin	A2	PLACEBO	56	contrast, md			R0024063:Table 2
STEP HFpEF DM	A1	SEMA_SC_2p4MG_QW	52	contrast, md	-2.500	1.429	R0020223:Table 2
STEP HFpEF DM	A2	PLACEBO	52	contrast, md			R0020223:Table 2
SURPASS-3	A1	TIRZ_SC_5MG_QW	40	contrast, md	-4.900	0.969	R0009496:Results
SURPASS-3	A4	INS_DEGLUDEC	40	contrast, md			R0009496:Results
SURPASS-5	A1	TIRZ_SC_5MG_QW	40	contrast, md	-4.400	1.735	R0009496:Results
SURPASS-5	A4	PLACEBO	40	contrast, md			R0009496:Results

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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