Network meta-analysis

Body weight change in kilograms (diabetes)

Type 2 diabetes (adults); background therapy: no glucose lowering drug (lifestyle only)

weeks 36 to 64 (target week 52)Not stated by the trialsDoses of a drug pooledMean difference

Randomized trials

Treatments

1,422

Participants

Trial arms

In plain language

Across 4 trials with 1,422 participants, 0 of 5 treatments had a clearly better result than placebo on body weight change in kilograms (diabetes), and for 5 the evidence could not tell them apart from placebo. The most favorable estimate was for Efpe sc: mean difference -1.44 kg (95% credible interval -6.48 to 3.62).

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 kg. 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
Efpe sc EFPE_SC	-1.44 (-6.48 to 3.62)	-8.33 to 5.50	-1.47 (-3.45 to 0.51)	Unclear
Semaglutide tablet SEMA_PO	-0.18 (-4.52 to 4.84)	-6.65 to 6.88	-0.22 (-0.92 to 0.47)	Unclear
Liraglutide injection LIRA_SC	1.59 (-2.37 to 6.40)	-4.69 to 8.72	1.50 (0.76 to 2.24)	Unclear
Albiglutide injection ALBI_SC	1.92 (-4.21 to 8.50)	-5.70 to 10.09	1.89 (0.94 to 2.85)	Unclear
Glibenclamide GLIBENCLAMIDE	3.37 (-2.15 to 10.24)	-3.90 to 12.11	3.21 (2.25 to 4.17)	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	EFPE_SC	SEMA_PO	LIRA_SC	ALBI_SC	GLIBENCLAMIDE
PLACEBO	PLACEBO	1.44 -3.62 to 6.48	0.18 -4.84 to 4.52	-1.59 -6.40 to 2.37	-1.92 -8.50 to 4.21	-3.37 -10.24 to 2.15
EFPE_SC	-1.44 -6.48 to 3.62	EFPE_SC	-1.28 -8.48 to 5.39	-3.05 -10.09 to 3.20	-3.34 -11.87 to 4.46	-4.80 -13.50 to 2.58
SEMA_PO	-0.18 -4.52 to 4.84	1.28 -5.39 to 8.48	SEMA_PO	-1.76 -6.62 to 2.82	-2.10 -8.34 to 4.43	-3.53 -10.55 to 2.64
LIRA_SC	1.59 -2.37 to 6.40	3.05 -3.20 to 10.09	1.76 -2.82 to 6.62	LIRA_SC	-0.32 -4.76 to 4.57	-1.77 -6.88 to 2.62
ALBI_SC	1.92 -4.21 to 8.50	3.34 -4.46 to 11.87	2.10 -4.43 to 8.34	0.32 -4.57 to 4.76	ALBI_SC	-1.42 -8.87 to 4.67
GLIBENCLAMIDE	3.37 -2.15 to 10.24	4.80 -2.58 to 13.50	3.53 -2.64 to 10.55	1.77 -2.62 to 6.88	1.42 -4.67 to 8.87	GLIBENCLAMIDE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 1.529 (95% CrI 0.067 to 5.077)
Residual deviance: 9.1 for 9 data points
DIC: 18.2 (pD 9.1)
Largest R-hat: 1.003
Smallest ESS: bulk 2,023, tail 2,705
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

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	Sex (percent female) effect modifier, prognostic factor; 3 of 4	Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 4 of 4	Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 4 of 4	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 2 of 4	Kidney function (eGFR) (mL/min/1.73 m2) prognostic factor, effect modifier; 2 of 4	Treatment duration (weeks) effect modifier; 4 of 4	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 4 of 4
NCT00393718 S000330	32.75	24.8	S0	100 region: all sites in Asia	not reported	52	not_reported
NCT01733758 S001075	not reported	25.82	S0	not reported	not reported	52	not_reported
PIONEER 9 S001943	21.4	25.9	S0	100	97	52	not_reported
AMPLITUDE-M S002081	46.06	34.2	S0	not reported	101.24	56	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 24.8 (GLIBENCLAMIDE vs LIRA_SC) to 34.2 (EFPE_SC vs PLACEBO) kg/m2; threshold 3
FlagBaseline, Sex: not reported by 1 of 4 trials
FlagBaseline, Sex: design means range from 21.4 (LIRA_SC vs PLACEBO vs SEMA_PO) to 46.1 (EFPE_SC vs PLACEBO) percent female; threshold 15
FlagBaseline, Asian ancestry or region: not reported by 2 of 4 trials
FlagBaseline, Kidney function (eGFR): not reported by 2 of 4 trials
NoteOutcome assessment, time point: selected time points span 52 to 56 weeks
NoteOutcome assessment, analysis set: mixed: completers 1, full_analysis 2, randomized 1
NoteData handling, input conversions: arms_combined 3

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
NCT00393718	52	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2006	age 20 or older; HbA1c 7.4 to 10.4 percent NGSP; with or without prior oral agents
NCT01733758	52	completers	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2013	Japanese adults; diet and exercise with or without one oral drug; HbA1c 7 to 10 percent after washout
PIONEER 9	52	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2017	Japanese adults 20 y or older; HbA1c 6.5 to 9.5 on one oral drug washed out, or 7.0 to 10.0 on diet and exercise
AMPLITUDE-M	56	randomized	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2017	type 2 diabetes on diet and exercise, HbA1c 7 to 10 percent, no glucose lowering drug in prior 3 months

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
NCT00393718	A1	LIRA_SC	52	arm, final	64.300	0.190	265		registry:outcomes
NCT00393718	A2	GLIBENCLAMIDE	52	arm, final	66.010	0.250	130		registry:outcomes
NCT01733758	A2+A3	ALBI_SC	52	arm, change	-0.106	0.133	283	arms_combined	registry:outcomes
NCT01733758	A4	LIRA_SC	52	arm, change	-0.500	0.276	95		registry:outcomes
PIONEER 9	A1+A2+A3	SEMA_PO	52	arm, change	-1.222	0.259	146	arms_combined	registry:outcomes
PIONEER 9	A4	LIRA_SC	52	arm, change	0.500	0.289	48		registry:outcomes
PIONEER 9	A5	PLACEBO	52	arm, change	-1.000	0.243	49		registry:outcomes
AMPLITUDE-M	A1+A2+A3	EFPE_SC	56	arm, change	-2.669	0.618	304	arms_combined	R0007136:Figure 2
AMPLITUDE-M	A4	PLACEBO	56	arm, change	-1.200	0.800	102		R0007136:Figure 2

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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