Network meta-analysis

Serious adverse events

Alcohol use disorder

longest follow-upRecorded harmsEach dose separatelyHazard ratio (from event counts)

Randomized trials

Treatments

175

Participants

Events

In plain language

Across 2 trials with 175 participants, 0 of 2 treatments had a clearly better result than placebo on serious adverse events, and for 2 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 0.5 mg subcutaneous once weekly: hazard ratio (from event counts) 0.55 (95% credible interval 0.01 to 41.43).

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

Hazard ratio (from event counts). Lower values favor the treatment.

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
Treatment	Bayesian HR (95% CrI)	95% prediction interval	Frequentist HR (95% CI)	Verdict
Semaglutide 0.5 mg subcutaneous once weekly SEMA_SC_0p5MG_QW	0.55 (0.01 to 41.43)	0.00 to 49.19		Unclear
Exenatide extended release 2 mg subcutaneous once weekly EXENER_SC_2MG_QW	1.35 (0.33 to 5.17)	0.21 to 8.58		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: 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 column	PLACEBO	SEMA_SC_0p5MG_QW	EXENER_SC_2MG_QW
PLACEBO	PLACEBO	1.81 0.02 to 200	0.74 0.19 to 3.03
SEMA_SC_0p5MG_QW	0.55 0.01 to 41.43	SEMA_SC_0p5MG_QW	0.41 0.00 to 37.02
EXENER_SC_2MG_QW	1.35 0.33 to 5.17	2.42 0.03 to 293	EXENER_SC_2MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.378 (95% CrI 0.088 to 1.586), log scale
Residual deviance: 2.4 for 4 data points
DIC: 4.4 (pD 2.0)
Largest R-hat: 1.001
Smallest ESS: bulk 3,302, tail 3,468
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.

FlagOutcome assessment, analysis set: confounded with design: randomized 1, safety 1
FlagOutcome assessment, proportion method: confounded with design: not stated 1, observed 1
NoteOutcome assessment, time point: selected time points span 10 to 36 weeks
NoteData handling, input conversions: count_from_percent 2

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
NCT05520775	10	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	non_industry	2022	age 21 to 65; current DSM-5 AUD not seeking treatment; BMI 23 or higher; no diabetes
EXALT	36	randomized	not stated	not stated	not stated	observed	not stated	not stated	double_blind	non_industry	2017	age 18 to 70; DSM-5 AUD and ICD-10 dependence; 5 or more heavy drinking days in past 30; 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
Trial	Arm	Treatment	Week	Data	Events / N	Flags	Source
NCT05520775	A1	PLACEBO	10	arm, events	0 / 24		R0005391:Supplement eTable 1
NCT05520775	A2	SEMA_SC_0p5MG_QW	10	arm, events	0 / 24		R0005391:Supplement eTable 1
EXALT	A1	PLACEBO	36	arm, events	12 / 65	count_from_percent	R0012402:Results
EXALT	A2	EXENER_SC_2MG_QW	36	arm, events	15 / 62	count_from_percent	R0012402:Results

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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