LivingGLP1
Network meta-analysis

SF-36 physical component summary change

Overweight or obesity without diabetes (adults)

weeks 20 to 130 (target week 52)Not stated by the trialsEach dose separatelyMean differenceConvergence criteria not all met
5
Randomized trials
9
Treatments
4,091
Participants
16
Trial arms

In plain language

Across 5 trials with 4,091 participants, 2 of 8 treatments had a clearly better result than placebo on SF-36 physical component summary change, and for 6 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 0.4 mg injection once daily: mean difference 3.82 points (95% credible interval 0.70 to 7.28).

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_SC_3p0MG_QDPLACEBOSEMA_SC_0p05MG_QDSEMA_SC_0p1MG_QDSEMA_SC_0p2MG_QDSEMA_SC_0p3MG_QDSEMA_SC_0p4MG_QDSEMA_SC_1p7MG_QWSEMA_SC_2p4MG_QW
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

Mean difference in points. Higher values favor the treatment.
-4-202468← favors referencefavors treatment →Semaglutide 0.4 mg injection onc…Semaglutide 0.2 mg injection onc…Semaglutide 0.3 mg injection onc…Liraglutide 3.0 mg subcutaneous …Semaglutide 0.1 mg injection onc…Semaglutide 2.4 mg subcutaneous …Semaglutide 0.05 mg injection on…Semaglutide 1.7 mg injection onc…
Versus Placebo. 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 MD (95% CrI)95% prediction intervalFrequentist MD (95% CI)Verdict
Semaglutide 0.4 mg injection once daily
SEMA_SC_0p4MG_QD
3.82 (0.70 to 7.28)0.22 to 7.903.73 (1.13 to 6.33)Better
Semaglutide 0.2 mg injection once daily
SEMA_SC_0p2MG_QD
3.45 (-0.33 to 7.46)-0.72 to 8.063.36 (0.09 to 6.63)Unclear
Semaglutide 0.3 mg injection once daily
SEMA_SC_0p3MG_QD
2.23 (-0.81 to 5.65)-1.36 to 6.212.10 (-0.34 to 4.54)Unclear
Liraglutide 3.0 mg subcutaneous once daily
LIRA_SC_3p0MG_QD
1.88 (0.46 to 4.11)-0.54 to 5.131.77 (1.27 to 2.27)Better
Semaglutide 0.1 mg injection once daily
SEMA_SC_0p1MG_QD
1.82 (-2.20 to 6.19)-2.60 to 6.611.73 (-1.97 to 5.43)Unclear
Semaglutide 2.4 mg subcutaneous once weekly
SEMA_SC_2p4MG_QW
0.73 (-0.64 to 2.07)-1.82 to 3.340.72 (0.06 to 1.39)Unclear
Semaglutide 0.05 mg injection once daily
SEMA_SC_0p05MG_QD
0.49 (-3.32 to 4.55)-3.70 to 5.100.38 (-2.98 to 3.75)Unclear
Semaglutide 1.7 mg injection once weekly
SEMA_SC_1p7MG_QW
-0.81 (-3.06 to 1.50)-3.81 to 2.40-0.81 (-2.20 to 0.58)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: mean difference 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 columnPLACEBOSEMA_SC_0p4MG_QDSEMA_SC_0p2MG_QDSEMA_SC_0p3MG_QDLIRA_SC_3p0MG_QDSEMA_SC_0p1MG_QDSEMA_SC_2p4MG_QWSEMA_SC_0p05MG_QDSEMA_SC_1p7MG_QW
PLACEBOPLACEBO-3.82
-7.28 to -0.70		-3.45
-7.46 to 0.33		-2.23
-5.65 to 0.81		-1.88
-4.11 to -0.46		-1.82
-6.19 to 2.20		-0.73
-2.07 to 0.64		-0.49
-4.55 to 3.32		0.81
-1.50 to 3.06
SEMA_SC_0p4MG_QD3.82
0.70 to 7.28		SEMA_SC_0p4MG_QD0.38
-3.64 to 4.37		1.59
-1.64 to 4.93		1.88
-1.32 to 5.07		2.01
-2.24 to 6.27		3.08
-0.11 to 6.96		3.34
-0.49 to 7.36		4.59
0.81 to 8.72
SEMA_SC_0p2MG_QD3.45
-0.33 to 7.46		-0.38
-4.37 to 3.64		SEMA_SC_0p2MG_QD1.22
-2.60 to 5.10		1.50
-2.25 to 5.27		1.60
-3.32 to 6.60		2.72
-1.25 to 7.09		2.99
-1.54 to 7.42		4.22
-0.11 to 8.97
SEMA_SC_0p3MG_QD2.23
-0.81 to 5.65		-1.59
-4.93 to 1.64		-1.22
-5.10 to 2.60		SEMA_SC_0p3MG_QD0.29
-2.83 to 3.38		0.39
-3.85 to 4.60		1.47
-1.73 to 5.37		1.74
-2.18 to 5.76		3.03
-0.74 to 7.12
LIRA_SC_3p0MG_QD1.88
0.46 to 4.11		-1.88
-5.07 to 1.32		-1.50
-5.27 to 2.25		-0.29
-3.38 to 2.83		LIRA_SC_3p0MG_QD0.11
-4.05 to 4.26		1.15
-0.64 to 4.01		1.44
-2.29 to 5.24		2.72
0.16 to 5.81
SEMA_SC_0p1MG_QD1.82
-2.20 to 6.19		-2.01
-6.27 to 2.24		-1.60
-6.60 to 3.32		-0.39
-4.60 to 3.85		-0.11
-4.26 to 4.05		SEMA_SC_0p1MG_QD1.11
-3.09 to 5.70		1.34
-3.51 to 6.24		2.63
-1.95 to 7.40
SEMA_SC_2p4MG_QW0.73
-0.64 to 2.07		-3.08
-6.96 to 0.11		-2.72
-7.09 to 1.25		-1.47
-5.37 to 1.73		-1.15
-4.01 to 0.64		-1.11
-5.70 to 3.09		SEMA_SC_2p4MG_QW0.25
-4.01 to 4.10		1.53
-0.76 to 3.70
SEMA_SC_0p05MG_QD0.49
-3.32 to 4.55		-3.34
-7.36 to 0.49		-2.99
-7.42 to 1.54		-1.74
-5.76 to 2.18		-1.44
-5.24 to 2.29		-1.34
-6.24 to 3.51		-0.25
-4.10 to 4.01		SEMA_SC_0p05MG_QD1.28
-2.93 to 6.00
SEMA_SC_1p7MG_QW-0.81
-3.06 to 1.50		-4.59
-8.72 to -0.81		-4.22
-8.97 to 0.11		-3.03
-7.12 to 0.74		-2.72
-5.81 to -0.16		-2.63
-7.40 to 1.95		-1.53
-3.70 to 0.76		-1.28
-6.00 to 2.93		SEMA_SC_1p7MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.488 (95% CrI 0.021 to 2.843)
Residual deviance
15.2 for 16 data points
DIC
29.5 (pD 14.2)
Largest R-hat
1.003
Smallest ESS
bulk 1,310, tail 1,676
Divergent transitions
1
Convergence
Not all met; read with caution
Priors
PR01 N(0, 40^2); PR03 N(0, 20^2); PR07 half normal(0, 4^2) on tau

Frequentist check (netmeta)

Method
inverse variance, REML, MD
Tau
0.000
I squared
0%
Q (total)
1.68 on 3.00000000000001 df, P = 0.641
Q (between designs)
1.44, P = 0.486

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.

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.
  • NoteOutcome assessment, time point: selected time points span 44 to 68 weeks
  • NoteOutcome assessment, definition: mixed: change in systolic blood pressure 1, not stated 4
  • NoteOutcome assessment, instrument: mixed: not stated 4, SF-36v2 1
  • NoteData handling, input conversions: arms_combined 2
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
NCT0127221956full_analysisnot statedSF-36v2not statednot statednot statednot stateddouble_blindindustry2011age 18 or more; BMI 30 or more, or 27 or more with hypertension or dyslipidemia; no diabetes; prediabetes allowed
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
STEP 668full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2019
NCT0245371152full_analysischange in systolic blood pressurenot statednot statednot statednot statednot stateddouble_blindindustry2015BMI 30 or more without diabetes

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the mean difference on the analysis scale against the trial's first row. Flags mark converted, combined or approximated inputs.
Trial data entering this analysis
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
NCT01272219A1LIRA_SC_3p0MG_QD56arm, change3.6600.1501,690R0026099:Table 2
NCT01272219A2PLACEBO56arm, change1.9300.210799R0026099:Table 2
STEP 3A1SEMA_SC_2p4MG_QW68arm, change3.2000.297407registry:outcomes
STEP 3A2PLACEBO68arm, change2.6000.455204registry:outcomes
STEP7A1SEMA_SC_2p4MG_QW44arm, change1.4000.338237registry:outcomes
STEP7A2PLACEBO44arm, change0.4000.511116registry:outcomes
STEP 6A1SEMA_SC_1p7MG_QW68arm, change-0.8000.60698registry:outcomes
STEP 6A2SEMA_SC_2p4MG_QW68arm, change0.7000.318192registry:outcomes
STEP 6A3PLACEBO68arm, change0.1000.530100registry:outcomes
NCT02453711A1SEMA_SC_0p05MG_QD52arm, change4.1601.48227registry:outcomes
NCT02453711A2SEMA_SC_0p1MG_QD52arm, change5.5101.67623registry:outcomes
NCT02453711A3SEMA_SC_0p2MG_QD52arm, change7.1401.42720registry:outcomes
NCT02453711A4+A6SEMA_SC_0p3MG_QD52arm, change5.8790.89453arms_combinedregistry:outcomes
NCT02453711A5+A7SEMA_SC_0p4MG_QD52arm, change7.5061.00457arms_combinedregistry:outcomes
NCT02453711A8LIRA_SC_3p0MG_QD52arm, change6.2101.02031registry:outcomes
NCT02453711A9PLACEBO52arm, change2.2901.53437registry: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.

Open in the NMA lab