Network meta-analysis

Body weight change in kilograms (diabetes)

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 trialsEach dose separatelyMean difference

Randomized trials

Treatments

353

Participants

Trial arms

In plain language

Across 3 trials with 353 participants, 1 of 3 treatments had a clearly better result than basal bolus insulin on body weight change in kilograms (diabetes), and for 2 the evidence could not tell them apart from basal bolus insulin. The most favorable estimate was for Semaglutide 1.0 mg subcutaneous once weekly: mean difference -10.16 kg (95% credible interval -14.74 to -4.01).

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 kg. 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	Verdict
Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW	-10.16 (-14.74 to -4.01)	-16.85 to -1.70	Better
IGlarLixi 2:1 pen subcutaneous once daily titrated IGLARLIXI2_SC_TIT_QD	-4.15 (-9.12 to 1.21)	-11.10 to 3.59	Unclear
Basal insulin sglt2i OTHER_ACTIVE_basal_insulin_sglt2i	-0.90 (-6.10 to 4.27)	-8.29 to 6.14	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_1p0MG_QW	IGLARLIXI2_SC_TIT_QD	OTHER_ACTIVE_basal_insulin_sglt2i
OTHER_ACTIVE_basal_bolus_insulin	OTHER_ACTIVE_basal_bolus_insulin	10.16 4.01 to 14.74	4.15 -1.21 to 9.12	0.90 -4.27 to 6.10
SEMA_SC_1p0MG_QW	-10.16 -14.74 to -4.01	SEMA_SC_1p0MG_QW	-6.03 -12.85 to 1.69	-9.31 -15.94 to -1.18
IGLARLIXI2_SC_TIT_QD	-4.15 -9.12 to 1.21	6.03 -1.69 to 12.85	IGLARLIXI2_SC_TIT_QD	-3.25 -10.06 to 4.29
OTHER_ACTIVE_basal_insulin_sglt2i	-0.90 -6.10 to 4.27	9.31 1.18 to 15.94	3.25 -4.29 to 10.06	OTHER_ACTIVE_basal_insulin_sglt2i

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 1.630 (95% CrI 0.084 to 5.479)
Residual deviance: 5.9 for 6 data points
DIC: 11.9 (pD 5.9)
Largest R-hat: 1.002
Smallest ESS: bulk 2,506, tail 2,895
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 25^2); PR03 N(0, 12.5^2); PR07 half normal(0, 2.5^2) on tau

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.

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	Sex (percent female) effect modifier, prognostic factor; 3 of 3	Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 3 of 3	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 1 of 3	Kidney function (eGFR) (mL/min/1.73 m2) prognostic factor, effect modifier; 2 of 3	Treatment duration (weeks) effect modifier; 3 of 3	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 3 of 3
TRANSITION-T2D S000460	35.2 median	41.33	S3	1.67	65.17 median	26	not_reported
IDEAL S002272	33.6	20.97	S3	not reported	not reported	24	standard
BEYOND S002277	32.03	58.73 100 minus male share	S3	not reported	77.18	104.28	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 32.0 (OTHER_ACTIVE_basal_bolus_insulin vs OTHER_ACTIVE_basal_insulin_sglt2i) to 35.2 (OTHER_ACTIVE_basal_bolus_insulin vs SEMA_SC_1p0MG_QW) kg/m2; threshold 3
FlagBaseline, Sex: design means range from 21.0 (IGLARLIXI2_SC_TIT_QD vs OTHER_ACTIVE_basal_bolus_insulin) to 58.7 (OTHER_ACTIVE_basal_bolus_insulin vs OTHER_ACTIVE_basal_insulin_sglt2i) percent female; threshold 15
FlagBaseline, Asian ancestry or region: not reported by 2 of 3 trials
FlagBaseline, Kidney function (eGFR): not reported by 1 of 3 trials
FlagBaseline, Treatment duration: design means range from 24.0 (IGLARLIXI2_SC_TIT_QD vs OTHER_ACTIVE_basal_bolus_insulin) to 104.3 (OTHER_ACTIVE_basal_bolus_insulin vs OTHER_ACTIVE_basal_insulin_sglt2i) weeks; threshold 26
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	1.500	0.816	20	R0018231:Supplement Table S3
TRANSITION-T2D	A2	SEMA_SC_1p0MG_QW	26	arm, change	-8.900	0.536	40	R0018231:Supplement Table S3
IDEAL	A1	IGLARLIXI2_SC_TIT_QD	24	arm, change	-4.780	0.651	45	R0003942:Results
IDEAL	A2	OTHER_ACTIVE_basal_bolus_insulin	24	arm, change	-0.530	0.569	45	R0003942:Results
BEYOND	A1	OTHER_ACTIVE_basal_bolus_insulin	26.07	arm, change	0.300	0.149	101	R0011577:Table 2
BEYOND	A3	OTHER_ACTIVE_basal_insulin_sglt2i	26.07	arm, change	-0.600	0.188	102	R0011577:Table 2

Rerun this analysis yourself

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