LivingGLP1
Network meta-analysis

Weight loss of 15 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
12
Randomized trials
8
Treatments
4,205
Participants
1,484
Events

In plain language

Across 12 trials with 4,205 participants, 5 of 7 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 Tirzepatide injection: odds ratio 28.56 (95% credible interval 9.11 to 62.51).

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_SCLIRA_SCOTHER_ACTIVE_bimagrumabPLACEBOSEMA_POSEMA_SCSTANDARD_CARETIRZ_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.
0.050.10.20.250.51245102050100← favors referencefavors treatment →Tirzepatide injectionBimasema scSemaglutide tabletSemaglutide injectionBimagrumabLiraglutide injectionStandard care or no added treatm…
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
Tirzepatide injection
TIRZ_SC
28.56 (9.11 to 62.51)6.24 to 83.9526.27 (11.33 to 60.93)Better
Bimasema sc
BIMASEMA_SC
22.13 (7.93 to 55.90)5.76 to 80.0924.82 (9.41 to 65.46)Better
Semaglutide tablet
SEMA_PO
17.47 (6.04 to 44.04)4.32 to 61.2018.91 (7.28 to 49.14)Better
Semaglutide injection
SEMA_SC
12.25 (8.06 to 19.67)4.85 to 33.1812.26 (7.85 to 19.14)Better
Bimagrumab
OTHER_ACTIVE_bimagrumab
5.02 (1.73 to 13.37)1.23 to 18.025.68 (1.95 to 16.58)Better
Liraglutide injection
LIRA_SC
1.47 (0.56 to 4.07)0.42 to 5.951.49 (0.54 to 4.15)Unclear
Standard care or no added treatment
STANDARD_CARE
0.30 (0.07 to 1.34)0.06 to 1.630.30 (0.06 to 1.45)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 columnPLACEBOTIRZ_SCBIMASEMA_SCSEMA_POSEMA_SCOTHER_ACTIVE_bimagrumabLIRA_SCSTANDARD_CARE
PLACEBOPLACEBO0.04
0.02 to 0.11		0.05
0.02 to 0.13		0.06
0.02 to 0.17		0.08
0.05 to 0.12		0.20
0.07 to 0.58		0.68
0.25 to 1.78		3.30
0.75 to 14.44
TIRZ_SC28.56
9.11 to 62.51		TIRZ_SC1.28
0.32 to 3.83		1.62
0.38 to 5.44		2.35
0.75 to 4.62		5.65
1.31 to 18.48		19.30
4.19 to 58.56		95.16
14.74 to 449
BIMASEMA_SC22.13
7.93 to 55.90		0.78
0.26 to 3.09		BIMASEMA_SC1.26
0.32 to 5.08		1.82
0.65 to 4.19		4.40
1.54 to 12.30		15.04
3.63 to 54.04		73.81
11.75 to 405
SEMA_PO17.47
6.04 to 44.04		0.62
0.18 to 2.63		0.79
0.20 to 3.11		SEMA_PO1.42
0.44 to 3.88		3.44
0.79 to 14.63		11.89
2.61 to 43.63		57.76
9.17 to 329
SEMA_SC12.25
8.06 to 19.67		0.43
0.22 to 1.34		0.55
0.24 to 1.53		0.70
0.26 to 2.29		SEMA_SC2.44
0.96 to 6.93		8.32
3.14 to 21.69		40.96
9.52 to 177
OTHER_ACTIVE_bimagrumab5.02
1.73 to 13.37		0.18
0.05 to 0.76		0.23
0.08 to 0.65		0.29
0.07 to 1.27		0.41
0.14 to 1.04		OTHER_ACTIVE_bimagrumab3.43
0.81 to 12.85		16.78
2.73 to 95.88
LIRA_SC1.47
0.56 to 4.07		0.05
0.02 to 0.24		0.07
0.02 to 0.28		0.08
0.02 to 0.38		0.12
0.05 to 0.32		0.29
0.08 to 1.24		LIRA_SC4.90
1.57 to 16.29
STANDARD_CARE0.30
0.07 to 1.34		0.01
0.00 to 0.07		0.01
0.00 to 0.09		0.02
0.00 to 0.11		0.02
0.01 to 0.10		0.06
0.01 to 0.37		0.20
0.06 to 0.64		STANDARD_CARE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.330 (95% CrI 0.085 to 0.850), log scale
Residual deviance
28.3 for 27 data points
DIC
49.9 (pD 21.6)
Largest R-hat
1.007
Smallest ESS
bulk 1,751, tail 2,636
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
0.403
I squared
41%
Q (total)
13.55 on 8 df, P = 0.094
Q (between designs)
5.79, P = 0.122

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
TrialType 2 diabetes share in weight trials (percent of participants)
effect modifier; 12 of 12
Baseline BMI or body weight (kg/m2)
effect modifier, prognostic factor; 7 of 12
Sex (percent female)
effect modifier, prognostic factor; 12 of 12
Treatment duration (weeks)
effect modifier; 12 of 12
Lifestyle co-intervention intensity (none standard intensive)
effect modifier, prognostic factor; 12 of 12
SURMOUNT-CN
S001086
0
population codes
body weight 91.8 kg
49.0552standard
SURMOUNT-5
S000093
0
population codes
39.464.6572standard
STEP 5
S000214
0
population codes
38.5577.6104standard
BARI-STEP
S000434
1041.582.8568standard
NCT05616013
S000715
0
population codes
37.357.3748standard
STEP 10
S000832
0
population codes
39.971.0152not_reported
STEP 3
S000988
0
population codes
3881.0168intensive
STEP7
S001288
0
population codes
not reported45.3344standard
OASIS 1
S001472
0
population codes
not reported72.7168not_reported
STEP 8
S001600
0
population codes
not reported78.468standard
STRIVE
S001687
35.545.9664.28104intensive
STEP 6
S002102
0
population codes
not reported36.9168not_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 5 of 12 trials
  • FlagBaseline, Baseline BMI or body weight: design means range from 37.3 (BIMASEMA_SC vs OTHER_ACTIVE_bimagrumab vs PLACEBO vs SEMA_SC) 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 (BIMASEMA_SC vs OTHER_ACTIVE_bimagrumab vs PLACEBO vs SEMA_SC) to 35.5 (LIRA_SC vs STANDARD_CARE) percent of participants; threshold 20
  • FlagBaseline, Sex: design means range from 49.0 (PLACEBO vs TIRZ_SC) to 78.4 (LIRA_SC vs PLACEBO vs SEMA_SC) percent female; threshold 15
  • FlagBaseline, Treatment duration: design means range from 48.0 (BIMASEMA_SC vs OTHER_ACTIVE_bimagrumab vs PLACEBO vs SEMA_SC) to 104.0 (LIRA_SC vs STANDARD_CARE) weeks; threshold 26
  • NoteOutcome assessment, time point: selected time points span 44 to 78 weeks
  • NoteOutcome assessment, analysis set: mixed: completers 3, full_analysis 7, modified_itt 1, other 1
  • NoteOutcome assessment, proportion method: mixed: not stated 9, observed 3
  • NoteRisk of bias, blinding: mixed: double_blind 9, open_label 3
  • NoteRisk of bias, funding: mixed: industry 11, mixed 1
  • NoteData handling, input conversions: arms_combined 5, count_from_percent 8
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
SURMOUNT-CN78completersnot statednot statednot statedobservednot statednot stateddouble_blindindustry2021Chinese adults; BMI 28 or more, or 24 or more with a weight related comorbidity; no diabetes
SURMOUNT-572othernot statednot statednot statedobservednot statednot statedopen_labelindustry2023adults; BMI 30 or more, or 27 with complication; no diabetes
STEP 552full_analysisnot statednot 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
BARI-STEP68modified_ittnot statednot statednot statednot statednot statednot stateddouble_blindmixed2022age 18 to 65; at least 1 year after primary bypass or sleeve; less than 20 percent weight loss from surgery
NCT0561601348completersnot statednot 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 1052full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2021Adults with obesity and prediabetes; diabetes excluded
STEP 368full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2018BMI 30 or more, or 27 with comorbidity; no type 2 diabetes
STEP744full_analysisnot statednot 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 168full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2021overweight or obesity
STEP 868full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2019age 18 or older; BMI 30 or higher, or 27 with a weight related comorbidity; no type 2 diabetes
STRIVE52completersnot statednot statednot statednot statednot statednot statedopen_labelindustry2017age 18 to 75; BMI 35 or more plus prediabetes, T2D, hypertension or sleep apnea; no insulin or GLP-1 RA
STEP 668full_analysisnot statednot 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
SURMOUNT-5A1TIRZ_SC72arm, responders228 / 318count_from_percentregistry:outcomes
SURMOUNT-5A2SEMA_SC72arm, responders143 / 318count_from_percentregistry:outcomes
STEP 5A1SEMA_SC52arm, responders78 / 149registry:outcomes
STEP 5A2PLACEBO52arm, responders7 / 129registry:outcomes
BARI-STEPA1PLACEBO68arm, responders2 / 29R0014003:Results
BARI-STEPA2SEMA_SC68arm, responders21 / 34R0014003:Results
NCT05616013A1PLACEBO48arm, responders2 / 35count_from_percentregistry:outcomes
NCT05616013A2+A3OTHER_ACTIVE_bimagrumab48arm, responders17 / 68count_from_percent;arms_combinedregistry:outcomes
NCT05616013A4+A5SEMA_SC48arm, responders40 / 96count_from_percent;arms_combinedregistry:outcomes
NCT05616013A6+A7+A8+A9BIMASEMA_SC48arm, responders99 / 167count_from_percent;arms_combinedregistry:outcomes
STEP 10A1SEMA_SC52arm, responders62 / 129registry:outcomes
STEP 10A2PLACEBO52arm, responders1 / 66registry:outcomes
STEP 3A1SEMA_SC68arm, responders208 / 373registry:outcomes
STEP 3A2PLACEBO68arm, responders25 / 189registry:outcomes
SURMOUNT-CNA1+A2TIRZ_SC78arm, responders26 / 103count_from_percent;arms_combinedR0007857:Results
SURMOUNT-CNA3PLACEBO78arm, responders2 / 39count_from_percentR0007857:Results
STEP7A1SEMA_SC44arm, responders82 / 238registry:outcomes
STEP7A2PLACEBO44arm, responders7 / 116registry:outcomes
OASIS 1A1SEMA_PO68arm, responders170 / 317registry:outcomes
OASIS 1A2PLACEBO68arm, responders17 / 295registry:outcomes
STEP 8A1SEMA_SC68arm, responders65 / 117registry:outcomes
STEP 8A2LIRA_SC68arm, responders14 / 117registry:outcomes
STEP 8A3PLACEBO68arm, responders5 / 78registry:outcomes
STRIVEA1STANDARD_CARE52arm, responders6 / 93R0020855:Table 2
STRIVEA2LIRA_SC52arm, responders51 / 201R0020855:Table 2
STEP 6A1+A2SEMA_SC68arm, responders103 / 291arms_combinedregistry:outcomes
STEP 6A3PLACEBO68arm, responders3 / 100registry:outcomes

Rerun this analysis yourself

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