Network meta-analysis

Weight loss of 5 percent or more

Overweight or obesity without diabetes (adults)

weeks 20 to 40 (target week 26)Not stated by the trialsDoses of a drug pooledOdds ratio

Randomized trials

Treatments

1,263

Participants

592

Events

In plain language

Across 6 trials with 1,263 participants, 4 of 5 treatments had a clearly better result than placebo on weight loss of 5 percent or more, and for 1 the evidence could not tell it apart from placebo. The most favorable estimate was for Mazdutide injection: odds ratio 49.66 (95% credible interval 13.63 to 199).

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 injection MAZD_SC	49.66 (13.63 to 199)	9.44 to 263	Better
Efpe sc EFPE_SC	21.85 (4.99 to 105)	3.48 to 138	Better
Exenatide extended release injection EXENER_SC	10.40 (1.61 to 97.45)	1.30 to 114	Better
Liraglutide injection LIRA_SC	3.66 (1.35 to 9.58)	0.90 to 14.10	Better
Standard care or no added treatment STANDARD_CARE	0.87 (0.21 to 3.39)	0.16 to 4.74	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	EFPE_SC	EXENER_SC	LIRA_SC	STANDARD_CARE
PLACEBO	PLACEBO	0.02 0.01 to 0.07	0.05 0.01 to 0.20	0.10 0.01 to 0.62	0.27 0.10 to 0.74	1.16 0.30 to 4.70
MAZD_SC	49.66 13.63 to 199	MAZD_SC	2.28 0.30 to 16.31	4.80 0.35 to 48.02	13.59 2.77 to 73.12	57.81 8.44 to 399
EFPE_SC	21.85 4.99 to 105	0.44 0.06 to 3.36	EFPE_SC	2.09 0.15 to 24.48	6.02 1.06 to 38.50	25.90 3.38 to 188
EXENER_SC	10.40 1.61 to 97.45	0.21 0.02 to 2.82	0.48 0.04 to 6.47	EXENER_SC	2.88 0.36 to 30.01	12.32 1.14 to 150
LIRA_SC	3.66 1.35 to 9.58	0.07 0.01 to 0.36	0.17 0.03 to 0.94	0.35 0.03 to 2.81	LIRA_SC	4.22 1.48 to 11.83
STANDARD_CARE	0.87 0.21 to 3.39	0.02 0.00 to 0.12	0.04 0.01 to 0.30	0.08 0.01 to 0.87	0.24 0.08 to 0.67	STANDARD_CARE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.296 (95% CrI 0.072 to 1.187), log scale
Residual deviance: 11.4 for 12 data points
DIC: 21.5 (pD 10.1)
Largest R-hat: 1.002
Smallest ESS: bulk 3,263, tail 2,731
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; 6 of 6	Type 2 diabetes share in weight trials (percent of participants) effect modifier; 6 of 6	Sex (percent female) effect modifier, prognostic factor; 6 of 6	Treatment duration (weeks) effect modifier; 6 of 6	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 6 of 6
NCT02075281 S000743	35.44	0 population codes	76.35	20	standard
NCT04904913 S001183	31.83	0 population codes	52.03	24	none
Dapalost S001235	35.4	0 population codes	61.25	24	standard
NCT05623839 S001559	32.5	0 population codes	50	20	none
STRIVE S001687	45.96	35.5	64.28	104	intensive
NCT01557166 S002315	39.15	0 population codes	28.1	32	standard

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, Baseline BMI or body weight: design means range from 32.2 (MAZD_SC vs PLACEBO) to 46.0 (LIRA_SC vs STANDARD_CARE) kg/m2; threshold 3
FlagBaseline, Type 2 diabetes share in weight trials: design means range from 0.0 (EFPE_SC vs PLACEBO) to 35.5 (LIRA_SC vs STANDARD_CARE) percent of participants; threshold 20
FlagBaseline, Sex: design means range from 28.1 (LIRA_SC vs PLACEBO) to 76.3 (EFPE_SC vs PLACEBO) percent female; threshold 15
FlagBaseline, Treatment duration: design means range from 20.0 (EFPE_SC vs PLACEBO) to 104.0 (LIRA_SC vs STANDARD_CARE) weeks; threshold 26
NoteOutcome assessment, time point: selected time points span 20 to 32 weeks
NoteOutcome assessment, analysis set: mixed: completers 2, full_analysis 3, modified_itt 1
NoteOutcome assessment, definition: mixed: body weight reduction of 5 percent or more 1, not stated 4, weight loss of 5% or more 1
NoteOutcome assessment, proportion method: mixed: not stated 3, not_stated 2, not_stated;observed 1
NoteRisk of bias, blinding: mixed: double_blind 5, open_label 1
NoteData handling, input conversions: arms_combined 3, count_from_percent 4

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
NCT02075281	20	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2014	age 18 to 64 years; BMI 30 to 42, or 27 to 30 with comorbidity; FPG below 7 mmol/L; HbA1c 6.5 percent or less; 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
Dapalost	24	full_analysis	body weight reduction of 5 percent or more	not stated	not stated	not_stated;observed	not stated	not stated	double_blind	industry	2014	age 18 to 70; BMI 30 to 45 kg/m2; no diabetes
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
STRIVE	32	completers	not stated	not stated	not stated	not stated	not stated	not stated	open_label	industry	2017	age 18 to 75; BMI 35 or more plus prediabetes, T2D, hypertension or sleep apnea; no insulin or GLP-1 RA
NCT01557166	32	full_analysis	weight loss of 5% or more	not stated	not stated	not_stated	not stated	not stated	double_blind	industry	2012	age 18 to 64; BMI 30 or more; AHI 15 or more; no diabetes; unable or unwilling to use CPAP

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
NCT02075281	A1	PLACEBO	20	arm, responders	2 / 60		R0011218:Figure 1
NCT02075281	A2+A3+A4+A5	EFPE_SC	20	arm, responders	116 / 235	arms_combined	R0011218:Figure 1
NCT04904913	A1+A2+A3	MAZD_SC	24	arm, responders	137 / 186	arms_combined	R0016107:Table 2
NCT04904913	A4	PLACEBO	24	arm, responders	3 / 62		R0016107:Table 2
Dapalost	A1	EXENER_SC	24	arm, responders	9 / 23		R0025222:Table 1
Dapalost	A2	PLACEBO	24	arm, responders	1 / 24		R0025627:Table 2
NCT05623839	A1	PLACEBO	27	arm, responders	0 / 6	count_from_percent	R0013210:Figure 2
NCT05623839	A2+A3	MAZD_SC	27	arm, responders	16 / 21	count_from_percent;arms_combined	R0013210:Figure 2
STRIVE	A1	STANDARD_CARE	32	arm, responders	34 / 79		R0020855:Supplement Table S4
STRIVE	A2	LIRA_SC	32	arm, responders	158 / 208		R0020855:Supplement Table S4
NCT01557166	A1	LIRA_SC	32	arm, responders	83 / 180	count_from_percent	R0026203:Results
NCT01557166	A2	PLACEBO	32	arm, responders	33 / 179	count_from_percent	R0026203:Results

Rerun this analysis yourself

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