Network meta-analysis

Constipation

Weight maintenance after a GLP-1 receptor agonist containing run in

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

Randomized trials

Treatments

429

Participants

Events

In plain language

Across 2 trials with 429 participants, 0 of 2 treatments had a clearly better result than placebo on constipation, and for 2 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 2.4 mg subcutaneous once weekly: hazard ratio (from event counts) 2.50 (95% credible interval 0.11 to 33.07).

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 2.4 mg subcutaneous once weekly SEMA_SC_2p4MG_QW	2.50 (0.11 to 33.07)	0.09 to 44.54		Unclear
Orforglipron maximum tolerated dose tablet once daily ORFO_PO_MTD_24-36_QD	3.18 (0.75 to 12.53)	0.47 to 19.95		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_2p4MG_QW	ORFO_PO_MTD_24-36_QD
PLACEBO	PLACEBO	0.40 0.03 to 8.76	0.31 0.08 to 1.33
SEMA_SC_2p4MG_QW	2.50 0.11 to 33.07	SEMA_SC_2p4MG_QW	0.78 0.03 to 14.01
ORFO_PO_MTD_24-36_QD	3.18 0.75 to 12.53	1.28 0.07 to 33.68	ORFO_PO_MTD_24-36_QD

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.378 (95% CrI 0.086 to 1.500), log scale
Residual deviance: 3.9 for 4 data points
DIC: 7.8 (pD 3.8)
Largest R-hat: 1.002
Smallest ESS: bulk 3,791, tail 3,179
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, intercurrent events (rescue): confounded with design: hypothetical 1, not stated 1
NoteOutcome assessment, time point: selected time points span 12 to 52 weeks
NoteData handling, input conversions: arms_combined 2, nonserious_only 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
STABLE Wt Loss	12	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2022	age 18 to 70; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c 6.5 percent or less
NCT06584916	52	safety	not stated	not stated	not stated	not stated	not stated	hypothetical	double_blind	industry	2024	adults without diabetes who completed SURMOUNT-5 on treatment with at least 5 percent weight loss; BMI above 22

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
STABLE Wt Loss	A3	SEMA_SC_2p4MG_QW	12	arm, events	1 / 10	nonserious_only	registry:adverse_events
STABLE Wt Loss	A4	PLACEBO	12	arm, events	1 / 43	nonserious_only	registry:adverse_events
NCT06584916	A1+A3	ORFO_PO_MTD_24-36_QD	52	arm, events	30 / 230	arms_combined	R0004461:Table 2
NCT06584916	A2+A4	PLACEBO	52	arm, events	6 / 146	arms_combined	R0004461:Table 2

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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