Network meta-analysis

Percent body weight change

Type 2 diabetes (adults); background therapy: one or more non insulin glucose lowering drugs

weeks 20 to 40 (target week 26)Hypothetical (as if everyone stayed on treatment)Doses of a drug pooledMean difference

Randomized trials

Treatments

1,499

Participants

Trial arms

In plain language

Across 6 trials with 1,499 participants, 0 of 6 treatments had a clearly better result than placebo on percent body weight change, and for 6 the evidence could not tell them apart from placebo. The most favorable estimate was for Loti po: mean difference -4.41 percentage points (95% credible interval -10.74 to 1.76).

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 percentage points. 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
Loti po LOTI_PO	-4.41 (-10.74 to 1.76)	-13.50 to 4.54	-4.44 (-5.78 to -3.10)	Unclear
Semaglutide injection SEMA_SC	-4.37 (-9.80 to 1.51)	-12.73 to 3.97	-4.38 (-5.37 to -3.40)	Unclear
Semaglutide tablet SEMA_PO	-1.62 (-9.89 to 7.09)	-11.67 to 9.40	-1.73 (-3.05 to -0.41)	Unclear
Dulaglutide injection DULA_SC	-1.13 (-10.65 to 9.45)	-12.31 to 11.03	-1.23 (-2.98 to 0.52)	Unclear
Liraglutide injection LIRA_SC	0.10 (-9.53 to 10.71)	-11.48 to 12.46	0.07 (-1.43 to 1.56)	Unclear
Sitagliptin SITAGLIPTIN	0.93 (-6.24 to 8.46)	-8.47 to 10.95	0.90 (-0.35 to 2.15)	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	LOTI_PO	SEMA_SC	SEMA_PO	DULA_SC	LIRA_SC	SITAGLIPTIN
PLACEBO	PLACEBO	4.41 -1.76 to 10.74	4.37 -1.51 to 9.80	1.62 -7.09 to 9.89	1.13 -9.45 to 10.65	-0.10 -10.71 to 9.53	-0.93 -8.46 to 6.24
LOTI_PO	-4.41 -10.74 to 1.76	LOTI_PO	-0.08 -8.90 to 8.28	-2.79 -13.73 to 7.63	-3.33 -15.80 to 7.94	-4.52 -16.73 to 6.74	-5.37 -15.01 to 3.68
SEMA_SC	-4.37 -9.80 to 1.51	0.08 -8.28 to 8.90	SEMA_SC	-2.76 -10.72 to 5.09	-3.27 -13.12 to 6.48	-4.50 -14.45 to 5.37	-5.29 -10.93 to 0.69
SEMA_PO	-1.62 -9.89 to 7.09	2.79 -7.63 to 13.73	2.76 -5.09 to 10.72	SEMA_PO	-0.53 -6.78 to 5.73	-1.76 -7.72 to 4.40	-2.58 -8.44 to 3.66
DULA_SC	-1.13 -10.65 to 9.45	3.33 -7.94 to 15.80	3.27 -6.48 to 13.12	0.53 -5.73 to 6.78	DULA_SC	-1.26 -9.73 to 7.77	-2.05 -10.23 to 6.96
LIRA_SC	0.10 -9.53 to 10.71	4.52 -6.74 to 16.73	4.50 -5.37 to 14.45	1.76 -4.40 to 7.72	1.26 -7.77 to 9.73	LIRA_SC	-0.79 -8.93 to 8.08
SITAGLIPTIN	0.93 -6.24 to 8.46	5.37 -3.68 to 15.01	5.29 -0.69 to 10.93	2.58 -3.66 to 8.44	2.05 -6.96 to 10.23	0.79 -8.08 to 8.93	SITAGLIPTIN

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 1.900 (95% CrI 0.101 to 6.644)
Residual deviance: 8.0 for 8 data points
DIC: 16.1 (pD 8.0)
Largest R-hat: 1.002
Smallest ESS: bulk 2,018, tail 2,649
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 35^2); PR03 N(0, 17.5^2); PR07 half normal(0, 3.5^2) 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 BMI or body weight (kg/m2) effect modifier, prognostic factor; 6 of 6	Sex (percent female) effect modifier, prognostic factor; 6 of 6	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 6 of 6	Kidney function (eGFR) (mL/min/1.73 m2) prognostic factor, effect modifier; 5 of 6	Treatment duration (weeks) effect modifier; 6 of 6	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 6 of 6
SUSTAIN 9 S000483	31.9	41.72	23.51	95.2	30	not_reported
PIONEER 4 S000133	32.94	48	13.4	95.8	52	not_reported
PIONEER 10 S000234	26.26	25.74	100	96.57	52	not_reported
NCT05579977 S000448	35.44	52.05	13.22	not reported	32	not_reported
PIONEER 12 S000522	28.58	41.7	75.22	103.5	26	not_reported
SUSTAIN S001311	27.8	42.5	85.03	109.33 median	30	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 26.3 (DULA_SC vs SEMA_PO) to 35.4 (LOTI_PO vs PLACEBO) kg/m2; threshold 3
FlagBaseline, Sex: design means range from 25.7 (DULA_SC vs SEMA_PO) to 52.1 (LOTI_PO vs PLACEBO) percent female; threshold 15
FlagBaseline, Asian ancestry or region: design means range from 13.2 (LOTI_PO vs PLACEBO) to 100.0 (DULA_SC vs SEMA_PO) percent Asian; threshold 30
NoteOutcome assessment, time point: selected time points span 20 to 30 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 5, modified_itt 1
NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 5, not stated 1
NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 5, not stated 1
NoteRisk of bias, blinding: mixed: double_blind 5, single_blind 1
NoteData handling, input conversions: arms_combined 2

Comparability items per trial
Trial	funding	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	start year	Eligibility
SUSTAIN 9	industry	30	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	2017	adults 18 or older (20 in Japan); HbA1c 7.0 to 10.5 percent; stable SGLT2i with or without metformin or SU
PIONEER 4	industry	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	2016	Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more
PIONEER 10	industry	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	single_blind	2017	Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
NCT05579977	industry	20	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	2022	age 18 to 75; T2D cohort on metformin, HbA1c 7.0 to 10.0, BMI 23 or more; obesity cohort BMI 30 or more without diabetes
PIONEER 12	industry	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	2019	adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent
SUSTAIN	industry	30	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	2017	Adults 18 or older, HbA1c 7.0 to 10.5 percent on metformin monotherapy, 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	Flags	Source
PIONEER 4	A1	SEMA_PO	26	contrast, md	-1.800	0.357			R0015836:Supplement Table S3
PIONEER 4	A2	LIRA_SC	26	contrast, md					R0015836:Supplement Table S3
PIONEER 10	A1	SEMA_PO	26	contrast, md	-0.500	0.587			R0018421:Supplement Table S5
PIONEER 10	A4	DULA_SC	26	contrast, md					R0018421:Supplement Table S5
NCT05579977	A10+A11+A12+A13+A9	LOTI_PO	20	arm, percent_change	-6.284	0.301	178	arms_combined	R0004106:Supplement Table S2
NCT05579977	A8	PLACEBO	20	arm, percent_change	-1.840	0.614	45		R0004106:Supplement Table S2
SUSTAIN 9	A1	SEMA_SC	30	contrast, md	-4.380	0.503			R0021710:Figure 3a
SUSTAIN 9	A2	PLACEBO	30	contrast, md					R0021710:Figure 3a
PIONEER 12	A1+A2+A3	SEMA_PO	26	arm, percent_change	-3.634	0.147	941	arms_combined	registry:outcomes
PIONEER 12	A4	SITAGLIPTIN	26	arm, percent_change	-1.000	0.164	335		registry:outcomes
SUSTAIN	A2	SEMA_SC	30	contrast, md	-5.280	0.390			R0014802:Table 2
SUSTAIN	A3	SITAGLIPTIN	30	contrast, md					R0014802:Table 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.

Open in the NMA lab