Network meta-analysis

Nausea

Polycystic ovary syndrome

longest follow-upRecorded harmsEach dose separatelyHazard ratio (from event counts)Separate part 2 of a disconnected network

Randomized trials

Treatments

118

Participants

Events

In plain language

Across 2 trials with 118 participants, 0 of 2 treatments had a clearly better result than standard care or no added treatment on nausea, 1 a clearly worse one, and for 1 the evidence could not tell it apart from standard care or no added treatment. The most favorable estimate was for Exenatide extended release 2 mg subcutaneous once weekly: hazard ratio (from event counts) 1.12 (95% credible interval 0.28 to 4.40).

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 Standard care or no added treatment

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

Versus Standard care or no added treatment, 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 Standard care or no added treatment
Treatment	Bayesian HR (95% CrI)	95% prediction interval	Frequentist HR (95% CI)	Verdict
Exenatide extended release 2 mg subcutaneous once weekly EXENER_SC_2MG_QW	1.12 (0.28 to 4.40)	0.15 to 7.87		Unclear
Dulaglutide 1.5 mg subcutaneous once weekly DULA_SC_1p5MG_QW	17.26 (1.78 to 401)	1.26 to 478		Worse

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	STANDARD_CARE	EXENER_SC_2MG_QW	DULA_SC_1p5MG_QW
STANDARD_CARE	STANDARD_CARE	0.89 0.23 to 3.61	0.06 0.00 to 0.56
EXENER_SC_2MG_QW	1.12 0.28 to 4.40	EXENER_SC_2MG_QW	0.06 0.00 to 0.94
DULA_SC_1p5MG_QW	17.26 1.78 to 401	15.75 1.06 to 496	DULA_SC_1p5MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.386 (95% CrI 0.085 to 1.664), log scale
Residual deviance: 4.3 for 4 data points
DIC: 7.4 (pD 3.1)
Largest R-hat: 1.001
Smallest ESS: bulk 3,886, tail 3,670
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.

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	Sex (percent female) effect modifier, prognostic factor; 1 of 2
NCT04876027 S000699	not reported
NCT04029272 S000952	100

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, Sex: not reported by 1 of 2 trials
NoteOutcome assessment, time point: selected time points span 12 to 26.07 weeks

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
NCT04876027	26.07	randomized	not stated	not stated	not stated	not stated	not stated	not stated	open_label	non_industry	2021	women 18 to 45, BMI 24 or higher, PCOS by Rotterdam criteria
NCT04029272	12	randomized	not stated	not stated	not stated	not stated	not stated	not stated	open_label	non_industry	2019	women 18 to 40 years; Rotterdam PCOS; BMI 25 or more; 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	Source
NCT04876027	A1	DULA_SC_1p5MG_QW	26.07	arm, events	8 / 35	R0009547:Table 3
NCT04876027	A2	STANDARD_CARE	26.07	arm, events	0 / 33	R0009547:Table 3
NCT04029272	A1	STANDARD_CARE	12	arm, events	10 / 25	R0011463:Table 4
NCT04029272	A2	EXENER_SC_2MG_QW	12	arm, events	11 / 25	R0011463:Table 4

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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