LivingGLP1
Network meta-analysis

Percent body weight change

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

weeks 40 to 104 (target week 68)Treatment policyEach dose separatelyMean difference
4
Randomized trials
8
Treatments
3,032
Participants
13
Trial arms

In plain language

Across 4 trials with 3,032 participants, 2 of 7 treatments had a clearly better result than placebo on percent body weight change, and for 5 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 14 mg oral once daily (original tablet): mean difference -3.86 percentage points (95% credible interval -6.15 to -1.32).

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.
DULA_SC_0p75MG_QWLIRA_SC_1p8MG_QDPLACEBOSEMA_PO_14MG_QDSEMA_PO_3MG_QDSEMA_PO_7MG_QDSEMA_PO_FLEX_QDSITAGLIPTIN
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.
-6-4-2024← favors treatmentfavors reference →Semaglutide 14 mg oral once dail…Semaglutide oral once daily (ori…Semaglutide 7 mg oral once daily…Liraglutide 1.8 mg subcutaneous …Semaglutide 3 mg oral once daily…SitagliptinDulaglutide 0.75 mg subcutaneous…
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
TreatmentBayesian MD (95% CrI)95% prediction intervalFrequentist MD (95% CI)Verdict
Semaglutide 14 mg oral once daily (original tablet)
SEMA_PO_14MG_QD
-3.86 (-6.15 to -1.32)-6.91 to -0.24-3.95 (-4.95 to -2.95)Better
Semaglutide oral once daily (original tablet), flexible dose: 3, 7 or 14 mg adjusted by HbA1c and tolerability
SEMA_PO_FLEX_QD
-3.28 (-6.88 to 1.06)-7.31 to 1.89-3.45 (-5.27 to -1.63)Unclear
Semaglutide 7 mg oral once daily (original tablet)
SEMA_PO_7MG_QD
-3.14 (-5.79 to -0.02)-6.38 to 0.98-3.28 (-4.45 to -2.11)Better
Liraglutide 1.8 mg subcutaneous once daily
LIRA_SC_1p8MG_QD
-2.21 (-4.44 to 0.17)-5.39 to 1.30-2.26 (-3.10 to -1.42)Unclear
Semaglutide 3 mg oral once daily (original tablet)
SEMA_PO_3MG_QD
-1.97 (-4.56 to 1.07)-5.36 to 1.86-2.13 (-3.27 to -0.99)Unclear
Sitagliptin
SITAGLIPTIN
-1.21 (-3.94 to 2.32)-4.75 to 3.44-1.35 (-2.51 to -0.19)Unclear
Dulaglutide 0.75 mg subcutaneous once weekly
DULA_SC_0p75MG_QW
-0.51 (-3.54 to 2.93)-4.18 to 3.82-0.70 (-2.21 to 0.81)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 columnPLACEBOSEMA_PO_14MG_QDSEMA_PO_FLEX_QDSEMA_PO_7MG_QDLIRA_SC_1p8MG_QDSEMA_PO_3MG_QDSITAGLIPTINDULA_SC_0p75MG_QW
PLACEBOPLACEBO3.86
1.32 to 6.15		3.28
-1.06 to 6.88		3.14
0.02 to 5.79		2.21
-0.17 to 4.44		1.97
-1.07 to 4.56		1.21
-2.32 to 3.94		0.51
-2.93 to 3.54
SEMA_PO_14MG_QD-3.86
-6.15 to -1.32		SEMA_PO_14MG_QD-0.57
-4.07 to 2.70		-0.72
-2.53 to 0.82		-1.66
-3.91 to 0.88		-1.88
-3.74 to -0.36		-2.64
-5.08 to -0.66		-3.34
-5.78 to -1.07
SEMA_PO_FLEX_QD-3.28
-6.88 to 1.06		0.57
-2.70 to 4.07		SEMA_PO_FLEX_QD-0.14
-3.28 to 3.15		-1.09
-4.87 to 3.46		-1.32
-4.56 to 2.09		-2.08
-4.75 to 0.60		-2.77
-6.45 to 1.18
SEMA_PO_7MG_QD-3.14
-5.79 to -0.02		0.72
-0.82 to 2.53		0.14
-3.15 to 3.28		SEMA_PO_7MG_QD-0.95
-3.64 to 2.28		-1.17
-2.90 to 0.60		-1.93
-4.22 to 0.20		-2.61
-4.97 to -0.20
LIRA_SC_1p8MG_QD-2.21
-4.44 to 0.17		1.66
-0.88 to 3.91		1.09
-3.46 to 4.87		0.95
-2.28 to 3.64		LIRA_SC_1p8MG_QD-0.22
-3.43 to 2.49		-0.99
-4.61 to 1.99		-1.67
-5.41 to 1.38
SEMA_PO_3MG_QD-1.97
-4.56 to 1.07		1.88
0.36 to 3.74		1.32
-2.09 to 4.56		1.17
-0.60 to 2.90		0.22
-2.49 to 3.43		SEMA_PO_3MG_QD-0.76
-3.02 to 1.29		-1.45
-3.74 to 0.94
SITAGLIPTIN-1.21
-3.94 to 2.32		2.64
0.66 to 5.08		2.08
-0.60 to 4.75		1.93
-0.20 to 4.22		0.99
-1.99 to 4.61		0.76
-1.29 to 3.02		SITAGLIPTIN-0.67
-3.45 to 2.35
DULA_SC_0p75MG_QW-0.51
-3.54 to 2.93		3.34
1.07 to 5.78		2.77
-1.18 to 6.45		2.61
0.20 to 4.97		1.67
-1.38 to 5.41		1.45
-0.94 to 3.74		0.67
-2.35 to 3.45		DULA_SC_0p75MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.496 (95% CrI 0.023 to 3.170)
Residual deviance
11.5 for 12 data points
DIC
22.6 (pD 11.2)
Largest R-hat
1.002
Smallest ESS
bulk 1,116, tail 1,064
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
I squared
0%
Q (total)
1.39 on 2 df, P = 0.498
Q (between designs)
1.39, P = 0.498

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
TrialBaseline BMI or body weight (kg/m2)
effect modifier, prognostic factor; 3 of 4
Sex (percent female)
effect modifier, prognostic factor; 4 of 4
Asian ancestry or region (percent Asian)
effect modifier, prognostic factor; 4 of 4
Kidney function (eGFR) (mL/min/1.73 m2)
prognostic factor, effect modifier; 3 of 4
Treatment duration (weeks)
effect modifier; 4 of 4
Lifestyle co-intervention intensity (none standard intensive)
effect modifier, prognostic factor; 4 of 4
PIONEER 4
S000133
32.944813.495.852not_reported
PIONEER 10
S000234
26.2625.7410096.5752not_reported
PIONEER 7
S001153
31.1943.4515.0894.36104not_reported
PIONEER 3
S002267
not reported47.1613.14not reported78not_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: not reported by 1 of 4 trials
  • FlagBaseline, Baseline BMI or body weight: design means range from 26.3 (DULA_SC_0p75MG_QW vs SEMA_PO_14MG_QD vs SEMA_PO_3MG_QD vs SEMA_PO_7MG_QD) to 32.9 (LIRA_SC_1p8MG_QD vs PLACEBO vs SEMA_PO_14MG_QD) kg/m2; threshold 3
  • FlagBaseline, Sex: design means range from 25.7 (DULA_SC_0p75MG_QW vs SEMA_PO_14MG_QD vs SEMA_PO_3MG_QD vs SEMA_PO_7MG_QD) to 48.0 (LIRA_SC_1p8MG_QD vs PLACEBO vs SEMA_PO_14MG_QD) percent female; threshold 15
  • FlagBaseline, Asian ancestry or region: design means range from 13.1 (SEMA_PO_14MG_QD vs SEMA_PO_3MG_QD vs SEMA_PO_7MG_QD vs SITAGLIPTIN) to 100.0 (DULA_SC_0p75MG_QW vs SEMA_PO_14MG_QD vs SEMA_PO_3MG_QD vs SEMA_PO_7MG_QD) percent Asian; threshold 30
  • FlagBaseline, Kidney function (eGFR): not reported by 1 of 4 trials
  • FlagBaseline, Treatment duration: design means range from 52.0 (DULA_SC_0p75MG_QW vs SEMA_PO_14MG_QD vs SEMA_PO_3MG_QD vs SEMA_PO_7MG_QD) to 104.0 (SEMA_PO_FLEX_QD vs SITAGLIPTIN) weeks; threshold 26
  • NoteOutcome assessment, time point: selected time points span 52 to 78 weeks
  • NoteOutcome assessment, analysis set: mixed: full_analysis 3, randomized 1
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 1, treatment_policy 3
  • NoteOutcome assessment, intercurrent events (rescue): mixed: not stated 1, treatment_policy 3
  • NoteRisk of bias, blinding: mixed: double_blind 2, open_label 1, single_blind 1
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
PIONEER 452full_analysisnot statednot statednot statednot statedtreatment_policytreatment_policydouble_blindindustry2016Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more
PIONEER 1052full_analysisnot statednot statednot statednot statedtreatment_policytreatment_policysingle_blindindustry2017Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
PIONEER 752randomizednot statednot statednot statednot statednot statednot statedopen_labelindustry2016age 18 or more; HbA1c 7.5 to 9.5 percent; one or two oral glucose lowering drugs
PIONEER 378full_analysisnot statednot statednot statednot statedtreatment_policytreatment_policydouble_blindindustry2016adults with T2D; HbA1c 7.0 to 10.5 percent; metformin with or without sulfonylurea

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
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
PIONEER 4A1SEMA_PO_14MG_QD52arm, percent_change-4.9400.377285registry:outcomes
PIONEER 4A2LIRA_SC_1p8MG_QD52arm, percent_change-3.2500.257284registry:outcomes
PIONEER 4A3PLACEBO52arm, percent_change-0.9900.346142registry:outcomes
PIONEER 10A1SEMA_PO_3MG_QD52arm, percent_change-0.0200.287131registry:outcomes
PIONEER 10A2SEMA_PO_7MG_QD52arm, percent_change-1.3400.415132registry:outcomes
PIONEER 10A3SEMA_PO_14MG_QD52arm, percent_change-2.3300.410130registry:outcomes
PIONEER 10A4DULA_SC_0p75MG_QW52arm, percent_change1.2500.50465registry:outcomes
PIONEER 7A3SEMA_PO_FLEX_QD52contrast, md-2.1000.714R0023369:Supplement Table S10
PIONEER 7A4SITAGLIPTIN52contrast, mdR0023369:Supplement Table S10
PIONEER 3A1SEMA_PO_3MG_QD78arm, percent_change-1.8700.226466registry:outcomes
PIONEER 3A2SEMA_PO_7MG_QD78arm, percent_change-2.9200.263465registry:outcomes
PIONEER 3A3SEMA_PO_14MG_QD78arm, percent_change-3.4700.248465registry:outcomes
PIONEER 3A4SITAGLIPTIN78arm, percent_change-0.9900.203467registry:outcomes

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