LivingGLP1
Network meta-analysis

Gallbladder and biliary disease

Overweight or obesity without diabetes (adults)

longest follow-upRecorded harmsEach dose separatelyHazard ratio (from event counts)
6
Randomized trials
9
Treatments
3,790
Participants
80
Events

In plain language

Across 6 trials with 3,790 participants, 0 of 8 treatments had a clearly better result than placebo on gallbladder and biliary disease, 1 a clearly worse one, and for 7 the evidence could not tell them apart from placebo. The most favorable estimate was for VK2735 5.0 mg injection once weekly: hazard ratio (from event counts) 0.36 (95% credible interval 0.00 to 12.81).

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.
LIRA_SC_3p0MG_QDMAZD_SC_16MG_QWOTHER_ACTIVE_cagrilintidePLACEBOSEMA_SC_2p4MG_QWVK2735_SC_10MG_QWVK2735_SC_15MG_QWVK2735_SC_2p5MG_QWVK2735_SC_5p0MG_QW
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 →VK2735 5.0 mg injection once wee…VK2735 10 mg injection once weeklyMazdutide 16 mg injection once w…Liraglutide 3.0 mg subcutaneous …Semaglutide 2.4 mg subcutaneous …CagrilintideVK2735 15 mg injection once weeklyVK2735 2.5 mg injection once wee…
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
VK2735 5.0 mg injection once weekly
VK2735_SC_5p0MG_QW
0.36 (0.00 to 12.81)0.00 to 13.55Unclear
VK2735 10 mg injection once weekly
VK2735_SC_10MG_QW
0.37 (0.01 to 13.19)0.01 to 15.53Unclear
Mazdutide 16 mg injection once weekly
MAZD_SC_16MG_QW
0.44 (0.01 to 32.08)0.00 to 33.89Unclear
Liraglutide 3.0 mg subcutaneous once daily
LIRA_SC_3p0MG_QD
1.91 (0.10 to 38.42)0.08 to 41.05Unclear
Semaglutide 2.4 mg subcutaneous once weekly
SEMA_SC_2p4MG_QW
2.38 (1.09 to 5.43)0.70 to 8.02Worse
Cagrilintide
OTHER_ACTIVE_cagrilintide
3.31 (0.37 to 58.12)0.32 to 63.95Unclear
VK2735 15 mg injection once weekly
VK2735_SC_15MG_QW
3.66 (0.18 to 84.60)0.15 to 96.92Unclear
VK2735 2.5 mg injection once weekly
VK2735_SC_2p5MG_QW
3.74 (0.16 to 78.44)0.13 to 92.62Unclear

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 columnPLACEBOVK2735_SC_5p0MG_QWVK2735_SC_10MG_QWMAZD_SC_16MG_QWLIRA_SC_3p0MG_QDSEMA_SC_2p4MG_QWOTHER_ACTIVE_cagrilintideVK2735_SC_15MG_QWVK2735_SC_2p5MG_QW
PLACEBOPLACEBO2.80
0.08 to 232		2.67
0.08 to 189		2.27
0.03 to 192		0.52
0.03 to 10.37		0.42
0.18 to 0.92		0.30
0.02 to 2.72		0.27
0.01 to 5.61		0.27
0.01 to 6.41
VK2735_SC_5p0MG_QW0.36
0.00 to 12.81		VK2735_SC_5p0MG_QW0.98
0.00 to 212		0.80
0.00 to 252		0.18
0.00 to 21.23		0.15
0.00 to 5.64		0.10
0.00 to 7.71		0.10
0.00 to 6.60		0.10
0.00 to 7.04
VK2735_SC_10MG_QW0.37
0.01 to 13.19		1.02
0.00 to 260		VK2735_SC_10MG_QW0.79
0.00 to 265		0.19
0.00 to 21.63		0.16
0.00 to 5.94		0.10
0.00 to 7.46		0.10
0.00 to 6.03		0.10
0.00 to 6.25
MAZD_SC_16MG_QW0.44
0.01 to 32.08		1.26
0.00 to 560		1.26
0.00 to 477		MAZD_SC_16MG_QW0.25
0.00 to 37.60		0.18
0.00 to 13.69		0.12
0.00 to 16.95		0.12
0.00 to 21.60		0.11
0.00 to 25.63
LIRA_SC_3p0MG_QD1.91
0.10 to 38.42		5.46
0.05 to 1044		5.23
0.05 to 891		4.05
0.03 to 967		LIRA_SC_3p0MG_QD0.78
0.04 to 17.62		0.58
0.03 to 4.84		0.50
0.01 to 36.71		0.51
0.01 to 36.98
SEMA_SC_2p4MG_QW2.38
1.09 to 5.43		6.80
0.18 to 537		6.39
0.17 to 489		5.41
0.07 to 499		1.28
0.06 to 27.06		SEMA_SC_2p4MG_QW0.71
0.04 to 7.66		0.64
0.03 to 15.91		0.65
0.03 to 16.63
OTHER_ACTIVE_cagrilintide3.31
0.37 to 58.12		10.24
0.13 to 1602		9.99
0.13 to 1403		8.18
0.06 to 1550		1.72
0.21 to 33.29		1.40
0.13 to 26.37		OTHER_ACTIVE_cagrilintide0.95
0.02 to 53.07		0.93
0.02 to 65.30
VK2735_SC_15MG_QW3.66
0.18 to 84.60		9.85
0.15 to 1520		10.00
0.17 to 1399		8.43
0.05 to 2033		1.99
0.03 to 152		1.56
0.06 to 39.26		1.06
0.02 to 53.07		VK2735_SC_15MG_QW0.99
0.03 to 34.41
VK2735_SC_2p5MG_QW3.74
0.16 to 78.44		9.92
0.14 to 1650		9.97
0.16 to 1445		8.85
0.04 to 1748		1.97
0.03 to 129		1.54
0.06 to 34.00		1.07
0.02 to 50.21		1.01
0.03 to 29.85		VK2735_SC_2p5MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.299 (95% CrI 0.080 to 1.012), log scale
Residual deviance
12.0 for 16 data points
DIC
20.9 (pD 8.9)
Largest R-hat
1.001
Smallest ESS
bulk 4,649, tail 4,417
Divergent transitions
0
Convergence
All criteria met
Priors
PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-1.87, 1.52^2) on tau^2 (Adverse events, pharm vs placebo control)

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 19 to 111 weeks
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 5, while_on_treatment 1
  • NoteOutcome assessment, intercurrent events (rescue): mixed: not stated 5, treatment_policy 1
  • NoteData handling, input conversions: arms_combined 2
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
STEP 175safetynot statednot statednot statednot statedwhile_on_treatmenttreatment_policydouble_blindindustry2018adults; BMI 30 or more, or 27 or more with a weight related condition; no diabetes; HbA1c below 6.5 percent
STEP 5111safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2018age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c below 6.5 percent
VENTURE19safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2023age over 18; BMI 30 or more, or 27 or more with comorbidity; BMI 50 or less; no diabetes
STEP 368safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2018BMI 30 or more, or 27 with comorbidity; no type 2 diabetes
NCT0385604726safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2019age 18 or older; BMI 30 or more, or 27 or more with hypertension or dyslipidemia; no diabetes
NCT0562383927safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2022age 18 to 70; BMI 27 to 50; HbA1c below 6.5 percent; no diabetes

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
STEP 1A1SEMA_SC_2p4MG_QW75arm, events34 / 1,306R0023399:Table 3
STEP 1A2PLACEBO75arm, events8 / 655R0023399:Table 3
STEP 5A1SEMA_SC_2p4MG_QW111arm, events4 / 152R0021896:Table 3
STEP 5A2PLACEBO111arm, events2 / 152R0021896:Table 3
VENTUREA1PLACEBO19arm, events0 / 35R0011224:Table 3
VENTUREA2VK2735_SC_2p5MG_QW19arm, events1 / 35R0011224:Table 3
VENTUREA3VK2735_SC_5p0MG_QW19arm, events0 / 35R0011224:Table 3
VENTUREA4VK2735_SC_10MG_QW19arm, events0 / 36R0011224:Table 3
VENTUREA5VK2735_SC_15MG_QW19arm, events1 / 35R0011224:Table 3
STEP 3A1SEMA_SC_2p4MG_QW68arm, events20 / 407R0013578:Table 1
STEP 3A2PLACEBO68arm, events3 / 204R0013578:Table 1
NCT03856047A1+A2+A3+A4+A5OTHER_ACTIVE_cagrilintide26arm, events6 / 506arms_combinedR0017871:Table 3
NCT03856047A6LIRA_SC_3p0MG_QD26arm, events1 / 99R0017871:Table 3
NCT03856047A7PLACEBO26arm, events0 / 101R0017871:Table 3
NCT05623839A1PLACEBO27arm, events0 / 8R0013210:Supplement Table S2
NCT05623839A2+A3MAZD_SC_16MG_QW27arm, events0 / 24arms_combinedR0013210:Supplement Table S2

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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