Network meta-analysis

HbA1c change

Type 2 diabetes (adults); background therapy: prandial, premixed or basal bolus insulin with or without other drugs

weeks 20 to 36 (target week 26)Not stated by the trialsDoses of a drug pooledMean difference

Randomized trials

Treatments

353

Participants

Trial arms

In plain language

Across 3 trials with 353 participants, 0 of 3 treatments had a clearly better result than basal bolus insulin on HbA1c change, and for 3 the evidence could not tell them apart from basal bolus insulin. The most favorable estimate was for Semaglutide injection: mean difference -0.48 percentage points (95% credible interval -1.46 to 0.58).

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 Basal bolus insulin

Mean difference in percentage points. Lower values favor the treatment.

Versus Basal bolus insulin. 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 Basal bolus insulin
Treatment	Bayesian MD (95% CrI)	95% prediction interval	Frequentist MD (95% CI)	Verdict
Semaglutide injection SEMA_SC	-0.48 (-1.46 to 0.58)	-1.92 to 1.02	-0.50 (-0.86 to -0.14)	Unclear
Insulin glargine with lixisenatide injection IGLARLIXI_SC	-0.12 (-1.14 to 0.92)	-1.60 to 1.27	-0.12 (-0.48 to 0.24)	Unclear
Basal insulin sglt2i OTHER_ACTIVE_basal_insulin_sglt2i	-0.10 (-1.07 to 0.89)	-1.55 to 1.27	-0.10 (-0.33 to 0.13)	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	OTHER_ACTIVE_basal_bolus_insulin	SEMA_SC	IGLARLIXI_SC	OTHER_ACTIVE_basal_insulin_sglt2i
OTHER_ACTIVE_basal_bolus_insulin	OTHER_ACTIVE_basal_bolus_insulin	0.48 -0.58 to 1.46	0.12 -0.92 to 1.14	0.10 -0.89 to 1.07
SEMA_SC	-0.48 -1.46 to 0.58	SEMA_SC	-0.36 -1.79 to 1.10	-0.39 -1.75 to 1.11
IGLARLIXI_SC	-0.12 -1.14 to 0.92	0.36 -1.10 to 1.79	IGLARLIXI_SC	-0.01 -1.49 to 1.38
OTHER_ACTIVE_basal_insulin_sglt2i	-0.10 -1.07 to 0.89	0.39 -1.11 to 1.75	0.01 -1.38 to 1.49	OTHER_ACTIVE_basal_insulin_sglt2i

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.316 (95% CrI 0.017 to 1.065)
Residual deviance: 5.9 for 6 data points
DIC: 11.9 (pD 5.9)
Largest R-hat: 1.002
Smallest ESS: bulk 2,162, tail 2,698
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 5^2); PR03 N(0, 2.5^2); PR07 half normal(0, 0.5^2) 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 HbA1c (percent) effect modifier, prognostic factor; 3 of 3	Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 3 of 3	Diabetes duration (years) effect modifier, prognostic factor; 3 of 3	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 1 of 3	Age (years) prognostic factor; 3 of 3	Treatment duration (weeks) effect modifier; 3 of 3
TRANSITION-T2D S000460	6.83 median	S3	18.17 median	1.67	68.3 median	26
IDEAL S002272	7.89	S3	17.51	not reported	66.16	24
BEYOND S002277	8.57	S3	17.07	not reported	61.73	104.28

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 HbA1c: design means range from 6.8 (OTHER_ACTIVE_basal_bolus_insulin vs SEMA_SC) to 8.6 (OTHER_ACTIVE_basal_bolus_insulin vs OTHER_ACTIVE_basal_insulin_sglt2i) percent; threshold 0.5
FlagBaseline, Asian ancestry or region: not reported by 2 of 3 trials
FlagBaseline, Treatment duration: design means range from 24.0 (IGLARLIXI_SC vs OTHER_ACTIVE_basal_bolus_insulin) to 104.3 (OTHER_ACTIVE_basal_bolus_insulin vs OTHER_ACTIVE_basal_insulin_sglt2i) weeks; threshold 26
FlagHeterogeneity, tau above threshold: tau 0.32 exceeds the outcome threshold 0.3; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 24 to 26.07 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 1, randomized 2
NoteRisk of bias, funding: mixed: industry 2, non_industry 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
TRANSITION-T2D	26	randomized	not stated	not stated	not stated	not stated	not stated	not stated	open_label	industry	2021	age 18 to 75; HbA1c 7.5 or lower on basal bolus insulin up to 120 U per day
IDEAL	24	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	open_label	industry	2021	age 18 to 80; MDI insulin with or without metformin or SGLT2i; HbA1c 9 or lower (10 if noncompliant); insulin dose 0.8 IU/kg or lower; C-peptide above lower limit
BEYOND	26.07	randomized	not stated	not stated	not stated	not stated	not stated	not stated	open_label	non_industry	2019	age over 35; HbA1c above 7.5 percent; basal bolus insulin 6 months or more; eGFR 60 or more

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
TRANSITION-T2D	A1	OTHER_ACTIVE_basal_bolus_insulin	26	arm, change	0.000	0.153	20	R0018231:Supplement Table S3
TRANSITION-T2D	A2	SEMA_SC	26	arm, change	-0.500	0.102	40	R0018231:Supplement Table S3
IDEAL	A1	IGLARLIXI_SC	24	arm, change	-0.490	0.140	45	R0003942:Results
IDEAL	A2	OTHER_ACTIVE_basal_bolus_insulin	24	arm, change	-0.370	0.120	45	R0003942:Results
BEYOND	A1	OTHER_ACTIVE_basal_bolus_insulin	26.07	arm, change	-0.600	0.080	101	R0011577:Table 2
BEYOND	A3	OTHER_ACTIVE_basal_insulin_sglt2i	26.07	arm, change	-0.700	0.089	102	R0011577:Table 2

Rerun this analysis yourself

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