LivingGLP1
Network meta-analysis

Weight loss of 20 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
10
Randomized trials
5
Treatments
3,545
Participants
789
Events

In plain language

Across 10 trials with 3,545 participants, 3 of 4 treatments had a clearly better result than placebo on weight loss of 20 percent or more, and for 1 the evidence could not tell it apart from placebo. The most favorable estimate was for Tirzepatide injection: odds ratio 40.35 (95% credible interval 17.02 to 89.78).

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.
LIRA_SCPLACEBOSEMA_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.
0.51245102050100← favors referencefavors treatment →Tirzepatide injectionSemaglutide tabletSemaglutide injectionLiraglutide injection
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
40.35 (17.02 to 89.78)13.39 to 112Better
Semaglutide tablet
SEMA_PO
17.00 (6.62 to 43.47)5.37 to 54.02Better
Semaglutide injection
SEMA_SC
15.74 (9.52 to 27.58)7.22 to 38.07Better
Liraglutide injection
LIRA_SC
1.59 (0.52 to 4.72)0.44 to 5.74Unclear

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_SCSEMA_POSEMA_SCLIRA_SC
PLACEBOPLACEBO0.02
0.01 to 0.06		0.06
0.02 to 0.15		0.06
0.04 to 0.11		0.63
0.21 to 1.92
TIRZ_SC40.35
17.02 to 89.78		TIRZ_SC2.36
0.67 to 8.21		2.55
1.21 to 4.75		25.30
7.49 to 85.67
SEMA_PO17.00
6.62 to 43.47		0.42
0.12 to 1.50		SEMA_PO1.08
0.35 to 3.12		10.76
2.57 to 45.41
SEMA_SC15.74
9.52 to 27.58		0.39
0.21 to 0.82		0.93
0.32 to 2.86		SEMA_SC9.99
3.72 to 28.87
LIRA_SC1.59
0.52 to 4.72		0.04
0.01 to 0.13		0.09
0.02 to 0.39		0.10
0.03 to 0.27		LIRA_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.227 (95% CrI 0.060 to 0.681), log scale
Residual deviance
18.8 for 21 data points
DIC
33.3 (pD 14.4)
Largest R-hat
1.002
Smallest ESS
bulk 3,149, tail 4,050
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
TrialBaseline BMI or body weight (kg/m2)
effect modifier, prognostic factor; 5 of 10
Type 2 diabetes share in weight trials (percent of participants)
effect modifier; 10 of 10
Sex (percent female)
effect modifier, prognostic factor; 10 of 10
Treatment duration (weeks)
effect modifier; 10 of 10
Lifestyle co-intervention intensity (none standard intensive)
effect modifier, prognostic factor; 10 of 10
SURMOUNT-5
S000093
39.40
population codes
64.6572standard
STEP 5
S000214
38.550
population codes
77.6104standard
BARI-STEP
S000434
41.51082.8568standard
STEP 10
S000832
39.90
population codes
71.0152not_reported
STEP 3
S000988
380
population codes
81.0168intensive
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 8
S001600
not reported0
population codes
78.468standard
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 5 of 10 trials
  • 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
  • NoteOutcome assessment, time point: selected time points span 44 to 78 weeks
  • NoteOutcome assessment, analysis set: mixed: completers 1, full_analysis 7, modified_itt 1, other 1
  • NoteOutcome assessment, proportion method: mixed: not stated 9, observed 1
  • NoteRisk of bias, blinding: mixed: double_blind 9, open_label 1
  • NoteRisk of bias, funding: mixed: industry 9, mixed 1
  • NoteData handling, input conversions: arms_combined 2, count_from_percent 2
Comparability items per trial
Trialproportion methodtime weeksanalysis setdefinitioninstrumentadjudicatedintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
SURMOUNT-5observed72othernot statednot statednot statednot statednot statedopen_labelindustry2023adults; BMI 30 or more, or 27 with complication; no diabetes
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
BARI-STEPnot stated68modified_ittnot 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
STEP 10not stated52full_analysisnot statednot statednot statednot statednot stateddouble_blindindustry2021Adults with obesity and prediabetes; diabetes excluded
STEP 3not stated68full_analysisnot statednot statednot statednot statednot stateddouble_blindindustry2018BMI 30 or more, or 27 with comorbidity; no type 2 diabetes
SURMOUNT-CNnot stated78completersnot 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 8not stated68full_analysisnot statednot statednot statednot statednot stateddouble_blindindustry2019age 18 or older; BMI 30 or higher, or 27 with a weight related comorbidity; no type 2 diabetes
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
SURMOUNT-5A1TIRZ_SC72arm, responders175 / 318count_from_percentregistry:outcomes
SURMOUNT-5A2SEMA_SC72arm, responders99 / 318count_from_percentregistry:outcomes
STEP 5A1SEMA_SC52arm, responders52 / 149registry:outcomes
STEP 5A2PLACEBO52arm, responders3 / 129registry:outcomes
BARI-STEPA1PLACEBO68arm, responders1 / 29R0014003:Results
BARI-STEPA2SEMA_SC68arm, responders16 / 34R0014003:Results
STEP 10A1SEMA_SC52arm, responders32 / 129registry:outcomes
STEP 10A2PLACEBO52arm, responders0 / 66registry:outcomes
STEP 3A1SEMA_SC68arm, responders133 / 373registry:outcomes
STEP 3A2PLACEBO68arm, responders7 / 189registry:outcomes
SURMOUNT-CNA1+A2TIRZ_SC78arm, responders15 / 103arms_combinedR0007857:Supplement Table S2
SURMOUNT-CNA3PLACEBO78arm, responders0 / 39R0007857:Supplement Table S2
STEP7A1SEMA_SC44arm, responders34 / 238registry:outcomes
STEP7A2PLACEBO44arm, responders2 / 116registry:outcomes
OASIS 1A1SEMA_PO68arm, responders107 / 317registry:outcomes
OASIS 1A2PLACEBO68arm, responders8 / 295registry:outcomes
STEP 8A1SEMA_SC68arm, responders45 / 117registry:outcomes
STEP 8A2LIRA_SC68arm, responders7 / 117registry:outcomes
STEP 8A3PLACEBO68arm, responders2 / 78registry:outcomes
STEP 6A1+A2SEMA_SC68arm, responders49 / 291arms_combinedregistry:outcomes
STEP 6A3PLACEBO68arm, responders2 / 100registry:outcomes

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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