LivingGLP1
Network meta-analysis

Gallbladder and biliary disease

Type 2 diabetes (adults)

longest follow-upRecorded harmsDoses of a drug pooledHazard ratio (from event counts)
8
Randomized trials
8
Treatments
2,485
Participants
26
Events

In plain language

Across 8 trials with 2,485 participants, 0 of 7 treatments had a clearly better result than placebo on gallbladder and biliary disease, and for 7 the evidence could not tell them apart from placebo. The most favorable estimate was for Sitagliptin: hazard ratio (from event counts) 0.23 (95% credible interval 0.00 to 4.99).

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.
DANU_PODULA_SCINS_GLARGINEORFO_POPLACEBOSEMA_POSEMA_SCSITAGLIPTIN
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

Hazard ratio (from event counts). Lower values favor the treatment.
0.010.020.050.10.20.250.51245102050100← favors treatmentfavors reference →SitagliptinOrforglipron tabletSemaglutide tabletDulaglutide injectionDanuglipron tabletInsulin glargineSemaglutide injection
Versus Placebo, log scale. 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 HR (95% CrI)95% prediction intervalFrequentist HR (95% CI)Verdict
Sitagliptin
SITAGLIPTIN
0.23 (0.00 to 4.99)0.00 to 5.71Unclear
Orforglipron tablet
ORFO_PO
0.40 (0.00 to 29.61)0.00 to 33.77Unclear
Semaglutide tablet
SEMA_PO
0.44 (0.01 to 12.04)0.01 to 13.91Unclear
Dulaglutide injection
DULA_SC
0.62 (0.02 to 16.52)0.02 to 19.73Unclear
Danuglipron tablet
DANU_PO
1.15 (0.05 to 49.28)0.04 to 56.05Unclear
Insulin glargine
INS_GLARGINE
1.38 (0.11 to 13.39)0.10 to 16.97Unclear
Semaglutide injection
SEMA_SC
4.17 (0.84 to 27.29)0.65 to 35.65Unclear

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: hazard ratio (from event counts) 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 columnPLACEBOSITAGLIPTINORFO_POSEMA_PODULA_SCDANU_POINS_GLARGINESEMA_SC
PLACEBOPLACEBO4.37
0.20 to 253		2.49
0.03 to 217		2.27
0.08 to 71.34		1.62
0.06 to 50.90		0.87
0.02 to 19.94		0.72
0.07 to 8.75		0.24
0.04 to 1.19
SITAGLIPTIN0.23
0.00 to 4.99		SITAGLIPTIN0.54
0.00 to 114		0.50
0.00 to 54.93		0.35
0.00 to 40.76		0.18
0.00 to 16.93		0.18
0.00 to 5.52		0.05
0.00 to 1.07
ORFO_PO0.40
0.00 to 29.61		1.85
0.01 to 589		ORFO_PO0.93
0.00 to 227		0.64
0.00 to 158		0.32
0.00 to 72.93		0.30
0.00 to 38.08		0.09
0.00 to 9.26
SEMA_PO0.44
0.01 to 12.04		1.99
0.02 to 340		1.08
0.00 to 287		SEMA_PO0.64
0.07 to 12.00		0.34
0.00 to 36.11		0.32
0.01 to 18.54		0.10
0.00 to 3.94
DULA_SC0.62
0.02 to 16.52		2.83
0.02 to 496		1.56
0.01 to 382		1.55
0.08 to 13.79		DULA_SC0.48
0.00 to 54.70		0.45
0.01 to 24.22		0.14
0.00 to 5.25
DANU_PO1.15
0.05 to 49.28		5.55
0.06 to 1350		3.11
0.01 to 968		2.92
0.03 to 423		2.07
0.02 to 301		DANU_PO0.89
0.02 to 70.37		0.27
0.01 to 16.36
INS_GLARGINE1.38
0.11 to 13.39		5.67
0.18 to 558		3.29
0.03 to 571		3.13
0.05 to 178		2.20
0.04 to 130		1.13
0.01 to 58.70		INS_GLARGINE0.32
0.04 to 1.87
SEMA_SC4.17
0.84 to 27.29		18.30
0.94 to 1383		11.18
0.11 to 1310		10.06
0.25 to 453		7.05
0.19 to 322		3.64
0.06 to 138		3.09
0.54 to 23.88		SEMA_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.320 (95% CrI 0.069 to 1.316), log scale
Residual deviance
12.3 for 16 data points
DIC
20.3 (pD 8.0)
Largest R-hat
1.002
Smallest ESS
bulk 2,921, tail 3,718
Divergent transitions
0
Convergence
All criteria met
Priors
PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2.1, 1.58^2) on tau^2 (Adverse events, pharm vs pharm)

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.

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.
  • NoteOutcome assessment, time point: selected time points span 14 to 57 weeks
  • NoteOutcome assessment, analysis set: mixed: randomized 1, safety 7
  • NoteOutcome assessment, definition: mixed: Hypoglycemia adverse event of special interest 1, level 3 severe hypoglycemia 1, not stated 4, severe by ADA or plasma glucose below 3.1 mmol/L with symptoms 1, Zero implied by no hypoglycemia of any kind 1
  • NoteOutcome assessment, adjudicated: mixed: not stated 7, yes 1
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 7, while_on_treatment 1
  • NoteOutcome assessment, intercurrent events (rescue): mixed: not stated 7, treatment_policy 1
  • NoteRisk of bias, blinding: mixed: double_blind 4, open_label 3, single_blind 1
  • NoteRisk of bias, funding: mixed: industry 7, not_reported 1
  • NoteData handling, input conversions: arms_combined 6
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
PIONEER 1057safetynot statednot statedyesnot statedwhile_on_treatmenttreatment_policysingle_blindindustry2017Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
NCT0551453545safetylevel 3 severe hypoglycemianot statednot statednot statednot statednot statedopen_labelindustry2022adults with T2D, BMI 25 or more, HbA1c 7 to 10 percent, basal insulin up to 40 U/day plus metformin with or without SGLT2i
NCT0398529320safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2019age 18 to 75; HbA1c 7 to 10.5 percent; BMI 22.5 (Asia) or 24.5 to 45.4; metformin or diet and exercise
NCT0548606549safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2022age 18 to 64; HbA1c 7.0 to 10.5; BMI 27 or more; on metformin
SUSTAIN™ 535safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2014age 18 or older (20 in Japan); HbA1c 7.0 to 10.0 percent; stable basal insulin with or without metformin; eGFR 30 or more
NCT0508644514safetyHypoglycemia adverse event of special interestnot statednot statednot statednot statednot stateddouble_blindindustry2021Japanese; age 20 to 70; BMI 20 to 35; HbA1c 7.0 to 10.0 diet only or 6.5 to 9.0 on one OAM, withdrawn 28 days
SUSTAIN™35safetysevere by ADA or plasma glucose below 3.1 mmol/L with symptomsnot statednot statednot statednot statednot statedopen_labelindustry2014Japanese; age 20 or older; HbA1c 6.5 to 9.5 percent on one OAD or 7.0 to 10.5 percent on diet and exercise
S00294626randomizedZero implied by no hypoglycemia of any kindnot statednot statednot statednot statednot statedopen_labelnot_reported2020age over 20; T2D on liraglutide 0.6 or 0.9 mg; no new diabetes drug for 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 hazard ratio (from event counts) on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.
Trial data entering this analysis
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
PIONEER 10A1+A2+A3SEMA_PO57arm, events3 / 393arms_combinedR0018421:Table 2
PIONEER 10A4DULA_SC57arm, events1 / 65R0018421:Table 2
NCT05514535A1SEMA_SC45arm, events5 / 288R0015842:Table 2
NCT05514535A2INS_GLARGINE45arm, events2 / 285R0015842:Table 2
NCT03985293A1PLACEBO20arm, events0 / 66R0006095:Results
NCT03985293A2+A3+A4+A5+A6DANU_PO20arm, events1 / 346arms_combinedR0006095:Results
NCT05486065A1+A2+A3SEMA_SC49arm, events6 / 185arms_combinedR0005510:Table 2
NCT05486065A4PLACEBO49arm, events0 / 60R0005510:Table 2
SUSTAIN™ 5A1+A2SEMA_SC35arm, events4 / 264arms_combinedR0012671:Table 2
SUSTAIN™ 5A3PLACEBO35arm, events0 / 133R0012671:Table 2
NCT05086445A1PLACEBO14arm, events0 / 11R0003844:Table 2
NCT05086445A2+A3+A4ORFO_PO14arm, events0 / 49arms_combinedR0003844:Table 2
SUSTAIN™A1+A2SEMA_SC35arm, events4 / 205arms_combinedR0014736:Supplement Table S5
SUSTAIN™A3SITAGLIPTIN35arm, events0 / 103R0014736:Supplement Table S5
S002946A1SEMA_SC26arm, events0 / 16R0006360:Supplement Table S2
S002946A2DULA_SC26arm, events0 / 16R0006360:Supplement Table S2

Rerun this analysis yourself

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