LivingGLP1
Network meta-analysis

Weight loss of 5 percent or more

Overweight or obesity without diabetes (adults)

weeks 40 to 104 (target week 68)Not stated by the trialsDoses of a drug pooledOdds ratio
8
Randomized trials
6
Treatments
2,402
Participants
1,588
Events

In plain language

Across 8 trials with 2,402 participants, 5 of 5 treatments had a clearly better result than placebo on weight loss of 5 percent or more. The most favorable estimate was for Bimasema sc: odds ratio 93.67 (95% credible interval 22.10 to 409).

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.
BIMASEMA_SCOTHER_ACTIVE_bimagrumabPLACEBOSEMA_POSEMA_SCTIRZ_SC
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.
1245102050100← favors referencefavors treatment →Bimasema scTirzepatide injectionSemaglutide injectionSemaglutide tabletBimagrumab
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
TreatmentBayesian OR (95% CrI)95% prediction intervalFrequentist OR (95% CI)Verdict
Bimasema sc
BIMASEMA_SC
93.67 (22.10 to 409)15.69 to 531121 (35.39 to 414)Better
Tirzepatide injection
TIRZ_SC
24.12 (6.74 to 78.43)4.49 to 11227.71 (12.36 to 62.11)Better
Semaglutide injection
SEMA_SC
17.23 (9.65 to 26.47)5.16 to 49.5014.14 (10.64 to 18.79)Better
Semaglutide tablet
SEMA_PO
14.70 (4.59 to 38.73)3.11 to 59.7216.15 (10.79 to 24.16)Better
Bimagrumab
OTHER_ACTIVE_bimagrumab
5.28 (1.56 to 15.12)1.05 to 21.395.71 (2.84 to 11.48)Better

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 columnPLACEBOBIMASEMA_SCTIRZ_SCSEMA_SCSEMA_POOTHER_ACTIVE_bimagrumab
PLACEBOPLACEBO0.01
0.00 to 0.05		0.04
0.01 to 0.15		0.06
0.04 to 0.10		0.07
0.03 to 0.22		0.19
0.07 to 0.64
BIMASEMA_SC93.67
22.10 to 409		BIMASEMA_SC3.98
0.61 to 25.21		5.51
1.41 to 24.36		6.53
1.12 to 40.60		17.87
4.02 to 90.70
TIRZ_SC24.12
6.74 to 78.43		0.25
0.04 to 1.64		TIRZ_SC1.41
0.38 to 5.39		1.65
0.34 to 8.38		4.55
0.94 to 24.61
SEMA_SC17.23
9.65 to 26.47		0.18
0.04 to 0.71		0.71
0.19 to 2.62		SEMA_SC1.16
0.37 to 3.88		3.22
1.10 to 10.32
SEMA_PO14.70
4.59 to 38.73		0.15
0.02 to 0.89		0.61
0.12 to 2.96		0.86
0.26 to 2.73		SEMA_PO2.77
0.59 to 13.30
OTHER_ACTIVE_bimagrumab5.28
1.56 to 15.12		0.06
0.01 to 0.25		0.22
0.04 to 1.07		0.31
0.10 to 0.91		0.36
0.08 to 1.69		OTHER_ACTIVE_bimagrumab

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.434 (95% CrI 0.203 to 0.912), log scale
Residual deviance
17.2 for 17 data points
DIC
32.9 (pD 15.6)
Largest R-hat
1.002
Smallest ESS
bulk 3,123, tail 4,081
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
Tau
0.000
I squared
0%
Q (total)
3.28 on 4 df, P = 0.512
Q (between designs)
2.32, P = 0.127

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; the between designs Q above is the global check.

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
TrialBaseline BMI or body weight (kg/m2)
effect modifier, prognostic factor; 4 of 8
Type 2 diabetes share in weight trials (percent of participants)
effect modifier; 8 of 8
Sex (percent female)
effect modifier, prognostic factor; 8 of 8
Treatment duration (weeks)
effect modifier; 8 of 8
Lifestyle co-intervention intensity (none standard intensive)
effect modifier, prognostic factor; 8 of 8
STEP 1
S000144
37.870
population codes
74.0768standard
STEP 5
S000214
38.550
population codes
77.6104standard
NCT05616013
S000715
37.30
population codes
57.3748standard
STEP 10
S000832
39.90
population codes
71.0152not_reported
SURMOUNT-CN
S001086
body weight 91.8 kg
0
population codes
49.0552standard
STEP7
S001288
not reported0
population codes
45.3344standard
OASIS 1
S001472
not reported0
population codes
72.7168not_reported
STEP 6
S002102
not reported0
population codes
36.9168not_reported

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: not reported by 4 of 8 trials
  • FlagBaseline, Sex: design means range from 49.0 (PLACEBO vs TIRZ_SC) to 72.7 (PLACEBO vs SEMA_PO) percent female; threshold 15
  • NoteOutcome assessment, time point: selected time points span 44 to 68 weeks
  • NoteOutcome assessment, analysis set: mixed: completers 1, full_analysis 6, modified_itt 1
  • NoteOutcome assessment, proportion method: mixed: not stated 6, not_stated 1, observed 1
  • NoteRisk of bias, blinding: mixed: double_blind 7, open_label 1
  • NoteData handling, input conversions: arms_combined 5, count_from_percent 6
Comparability items per trial
Trialinstrumenttime weeksanalysis setdefinitionadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
STEP 1not stated68full_analysisnot statednot statednot statednot statednot stateddouble_blindindustry2018adults; BMI 30 or more, or 27 or more with a weight related condition; no diabetes; HbA1c below 6.5 percent
STEP 5not stated52full_analysisnot statednot statednot statednot statednot stateddouble_blindindustry2018age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c below 6.5 percent
NCT05616013not stated48completersnot statednot statedobservednot statednot statedopen_labelindustry2022adults 18 to 80; BMI 30 or more, or 27 or more with comorbidity; no diabetes (HbA1c below 6.5 percent); weight below 150 kg
STEP 10not stated52full_analysisnot statednot statednot statednot statednot stateddouble_blindindustry2021Adults with obesity and prediabetes; diabetes excluded
SURMOUNT-CNnot stated52modified_ittnot statednot statednot_statednot statednot stateddouble_blindindustry2021Chinese adults; BMI 28 or more, or 24 or more with a weight related comorbidity; no diabetes
STEP7not stated44full_analysisnot statednot statednot statednot statednot stateddouble_blindindustry2020age 18 or older; BMI 30 or more, or 27 or more with a weight related comorbidity including T2D
OASIS 1not stated68full_analysisnot statednot statednot statednot statednot stateddouble_blindindustry2021overweight or obesity
STEP 6not stated68full_analysisnot statednot statednot statednot statednot stateddouble_blindindustry2019

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
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
STEP 1A1SEMA_SC68contrast, or3.6120.142registry:outcomes
STEP 1A2PLACEBO68contrast, orregistry:outcomes
STEP 5A1SEMA_SC52arm, responders132 / 149registry:outcomes
STEP 5A2PLACEBO52arm, responders38 / 129registry:outcomes
NCT05616013A1PLACEBO48arm, responders14 / 35count_from_percentregistry:outcomes
NCT05616013A2+A3OTHER_ACTIVE_bimagrumab48arm, responders49 / 68count_from_percent;arms_combinedregistry:outcomes
NCT05616013A4+A5SEMA_SC48arm, responders80 / 96count_from_percent;arms_combinedregistry:outcomes
NCT05616013A6+A7+A8+A9BIMASEMA_SC48arm, responders164 / 167count_from_percent;arms_combinedregistry:outcomes
STEP 10A1SEMA_SC52arm, responders111 / 129registry:outcomes
STEP 10A2PLACEBO52arm, responders17 / 66registry:outcomes
SURMOUNT-CNA1+A2TIRZ_SC52arm, responders127 / 138count_from_percent;arms_combinedregistry:outcomes
SURMOUNT-CNA3PLACEBO52arm, responders20 / 68count_from_percentregistry:outcomes
STEP7A1SEMA_SC44arm, responders203 / 238registry:outcomes
STEP7A2PLACEBO44arm, responders36 / 116registry:outcomes
OASIS 1A1SEMA_PO68arm, responders269 / 317registry:outcomes
OASIS 1A2PLACEBO68arm, responders76 / 295registry:outcomes
STEP 6A1+A2SEMA_SC68arm, responders231 / 291arms_combinedregistry:outcomes
STEP 6A3PLACEBO68arm, responders21 / 100registry:outcomes

Rerun this analysis yourself

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