Network meta-analysis

Weight loss of 15 percent or more

Overweight or obesity without diabetes (adults)

weeks 20 to 40 (target week 26)Not stated by the trialsEach dose separatelyOdds ratio

Randomized trials

Treatments

275

Participants

Events

In plain language

Across 2 trials with 275 participants, 2 of 4 treatments had a clearly better result than placebo on weight loss of 15 percent or more, and for 2 the evidence could not tell them apart from placebo. The most favorable estimate was for Mazdutide 6 mg subcutaneous once weekly: odds ratio 17.29 (95% credible interval 2.60 to 133).

Higher 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

Odds ratio. Higher 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 OR (95% CrI)	95% prediction interval	Verdict
Mazdutide 6 mg subcutaneous once weekly MAZD_SC_6MG_QW	17.29 (2.60 to 133)	1.73 to 175	Better
Mazdutide 16 mg injection once weekly MAZD_SC_16MG_QW	11.02 (0.96 to 272)	0.71 to 340	Unclear
Mazdutide 4.5 mg subcutaneous once weekly MAZD_SC_4p5MG_QW	9.08 (1.43 to 73.39)	0.96 to 94.14	Better
Mazdutide 3 mg subcutaneous once weekly MAZD_SC_3MG_QW	5.00 (0.73 to 42.06)	0.48 to 55.46	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: odds ratio 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	MAZD_SC_6MG_QW	MAZD_SC_16MG_QW	MAZD_SC_4p5MG_QW	MAZD_SC_3MG_QW
PLACEBO	PLACEBO	0.06 0.01 to 0.38	0.09 0.00 to 1.04	0.11 0.01 to 0.70	0.20 0.02 to 1.37
MAZD_SC_6MG_QW	17.29 2.60 to 133	MAZD_SC_6MG_QW	1.51 0.05 to 39.41	1.90 0.48 to 7.70	3.44 0.75 to 15.21
MAZD_SC_16MG_QW	11.02 0.96 to 272	0.66 0.03 to 22.09	MAZD_SC_16MG_QW	1.26 0.05 to 46.74	2.31 0.09 to 84.03
MAZD_SC_4p5MG_QW	9.08 1.43 to 73.39	0.53 0.13 to 2.07	0.79 0.02 to 19.43	MAZD_SC_4p5MG_QW	1.80 0.37 to 8.59
MAZD_SC_3MG_QW	5.00 0.73 to 42.06	0.29 0.07 to 1.33	0.43 0.01 to 10.93	0.56 0.12 to 2.69	MAZD_SC_3MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.336 (95% CrI 0.070 to 1.533), log scale
Residual deviance: 7.8 for 6 data points
DIC: 12.0 (pD 4.2)
Largest R-hat: 1.001
Smallest ESS: bulk 3,109, tail 3,413
Divergent transitions: 0
Convergence: All criteria met
Priors: PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2.29, 1.53^2) on tau^2 (General physical health indicators, 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	Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 2 of 2	Type 2 diabetes share in weight trials (percent of participants) effect modifier; 2 of 2	Sex (percent female) effect modifier, prognostic factor; 2 of 2	Treatment duration (weeks) effect modifier; 2 of 2	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 2 of 2
NCT05623839 S001559	32.5	0 population codes	50	20	none
NCT04904913 S001183	31.83	0 population codes	52.03	24	none

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: completers 1, modified_itt 1
FlagOutcome assessment, proportion method: confounded with design: not stated 1, not_stated 1
NoteOutcome assessment, time point: selected time points span 24 to 27 weeks
NoteData handling, input conversions: arms_combined 1, 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
NCT05623839	27	completers	not stated	not stated	not stated	not_stated	not stated	not stated	double_blind	industry	2022	age 18 to 70; BMI 27 to 50; HbA1c below 6.5 percent; no diabetes
NCT04904913	24	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2021	Chinese adults 18 to 75; BMI 28 or more, or 24 or more with comorbidity or hyperphagia; no diabetes, HbA1c below 6.5

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the odds ratio 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
NCT04904913	A1	MAZD_SC_3MG_QW	24	arm, responders	6 / 62		R0016107:Table 2
NCT04904913	A2	MAZD_SC_4p5MG_QW	24	arm, responders	10 / 63		R0016107:Table 2
NCT04904913	A3	MAZD_SC_6MG_QW	24	arm, responders	16 / 61		R0016107:Table 2
NCT04904913	A4	PLACEBO	24	arm, responders	0 / 62		R0016107:Table 2
NCT05623839	A1	PLACEBO	27	arm, responders	0 / 6	count_from_percent	R0013210:Figure 2
NCT05623839	A2+A3	MAZD_SC_16MG_QW	27	arm, responders	9 / 21	count_from_percent;arms_combined	R0013210:Figure 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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