Network meta-analysis

Weight loss of 5 percent or more

Overweight or obesity without diabetes (adults)

weeks 104 to 182 (target week 104)Treatment policyEach dose separatelyOdds ratio

Randomized trials

Treatments

272

Participants

155

Events

In plain language

Across 2 trials with 272 participants, 1 of 2 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 Semaglutide 2.4 mg subcutaneous once weekly: odds ratio 6.13 (95% credible interval 1.80 to 16.00).

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	Frequentist OR (95% CI)	Verdict
Semaglutide 2.4 mg subcutaneous once weekly SEMA_SC_2p4MG_QW	6.13 (1.80 to 16.00)	1.11 to 23.99	6.42 (3.77 to 10.94)	Better
Liraglutide 3.0 mg subcutaneous once daily LIRA_SC_3p0MG_QD	0.36 (0.12 to 1.30)	0.08 to 1.97		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	SEMA_SC_2p4MG_QW	LIRA_SC_3p0MG_QD
PLACEBO	PLACEBO	0.16 0.06 to 0.56	2.75 0.77 to 8.54
SEMA_SC_2p4MG_QW	6.13 1.80 to 16.00	SEMA_SC_2p4MG_QW	16.70 2.79 to 74.54
LIRA_SC_3p0MG_QD	0.36 0.12 to 1.30	0.06 0.01 to 0.36	LIRA_SC_3p0MG_QD

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.312 (95% CrI 0.071 to 1.334), log scale
Residual deviance: 2.9 for 3 data points
DIC: 5.9 (pD 2.9)
Largest R-hat: 1.001
Smallest ESS: bulk 2,980, tail 2,528
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)

Frequentist check (netmeta)

Method: inverse variance, REML, OR
Q (total): 0.00 on 0 df

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
STEP 5 S000214	38.55	0 population codes	77.6	104	standard
S-LITE S000371	32.62	0 population codes	64.51	52	intensive

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 32.6 (LIRA_SC_3p0MG_QD vs PLACEBO) to 38.6 (PLACEBO vs SEMA_SC_2p4MG_QW) kg/m2; threshold 3
FlagBaseline, Treatment duration: design means range from 52.0 (LIRA_SC_3p0MG_QD vs PLACEBO) to 104.0 (PLACEBO vs SEMA_SC_2p4MG_QW) weeks; threshold 26
FlagBaseline, Lifestyle co-intervention intensity: each design has a different category: LIRA_SC_3p0MG_QD vs PLACEBO = intensive; PLACEBO vs SEMA_SC_2p4MG_QW = standard
FlagOutcome assessment, analysis set: confounded with design: full_analysis 1, other 1
FlagOutcome assessment, definition: confounded with design: not stated 1, weight loss of at least 5 percent of initial weight before the diet (week -8), assessed at week 104 1
FlagOutcome assessment, intercurrent events (discontinuation): confounded with design: not stated 1, treatment_policy 1
FlagOutcome assessment, intercurrent events (rescue): confounded with design: not stated 1, treatment_policy 1
FlagRisk of bias, funding: confounded with design: industry 1, mixed 1

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
STEP 5	104	full_analysis	not stated	not stated	not stated	not stated	treatment_policy	treatment_policy	double_blind	industry	2018	age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c below 6.5 percent
S-LITE	104	other	weight loss of at least 5 percent of initial weight before the diet (week -8), assessed at week 104	not stated	not stated	not stated	not stated	not stated	double_blind	mixed	2016	age 18 to 65; BMI 32 to 43; no diabetes; at least 5 percent loss on 8 week low calorie diet

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	Value	SE	Events / N	Source
STEP 5	A1	SEMA_SC_2p4MG_QW	104	arm, responders			111 / 144	R0021896:Table 2
STEP 5	A2	PLACEBO	104	arm, responders			44 / 128	R0021896:Table 2
S-LITE	A2	PLACEBO	104	contrast, or	1.065	0.414		R0014026:Results
S-LITE	A3	LIRA_SC_3p0MG_QD	104	contrast, or				R0014026: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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