LivingGLP1
Network meta-analysis

Weight loss of 10 percent or more

Overweight or obesity without diabetes (adults)

weeks 20 to 40 (target week 26)Not stated by the trialsEach dose separatelyOdds ratio
6
Randomized trials
12
Treatments
1,265
Participants
310
Events

In plain language

Across 6 trials with 1,265 participants, 6 of 11 treatments had a clearly better result than placebo on weight loss of 10 percent or more, and for 5 the evidence could not tell them apart from placebo. The most favorable estimate was for Mazdutide 6 mg subcutaneous once weekly: odds ratio 34.09 (95% credible interval 3.72 to 218).

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.
EFPE_SC_4MG_QWEFPE_SC_6MG_Q2WEFPE_SC_6MG_QWEFPE_SC_8MG_Q2WEXENER_SC_2-10MG_QWLIRA_SC_3p0MG_QDMAZD_SC_16MG_QWMAZD_SC_3MG_QWMAZD_SC_4p5MG_QWMAZD_SC_6MG_QWPLACEBOSTANDARD_CARE
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.
0.20.250.51245102050100← favors referencefavors treatment →Mazdutide 6 mg subcutaneous once…Mazdutide 4.5 mg subcutaneous on…Mazdutide 16 mg injection once w…Liraglutide 3.0 mg subcutaneous …Efpeglenatide 6 mg subcutaneous …Mazdutide 3 mg subcutaneous once…Exenatide extended release and d…Efpeglenatide 6 mg injection eve…Efpeglenatide 8 mg injection eve…Efpeglenatide 4 mg subcutaneous …Standard 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
Mazdutide 6 mg subcutaneous once weekly
MAZD_SC_6MG_QW
34.09 (3.72 to 218)2.34 to 287Better
Mazdutide 4.5 mg subcutaneous once weekly
MAZD_SC_4p5MG_QW
31.82 (3.99 to 207)2.05 to 289Better
Mazdutide 16 mg injection once weekly
MAZD_SC_16MG_QW
17.83 (1.40 to 409)0.93 to 557Better
Liraglutide 3.0 mg subcutaneous once daily
LIRA_SC_3p0MG_QD
13.05 (2.47 to 55.36)1.24 to 89.35Better
Efpeglenatide 6 mg subcutaneous once weekly
EFPE_SC_6MG_QW
8.25 (1.22 to 42.60)0.69 to 61.74Better
Mazdutide 3 mg subcutaneous once weekly
MAZD_SC_3MG_QW
8.00 (1.04 to 52.62)0.59 to 70.29Better
Exenatide extended release and dapagliflozin 2 to 10 mg injection once weekly
EXENER_SC_2-10MG_QW
7.23 (0.51 to 188)0.39 to 223Unclear
Efpeglenatide 6 mg injection every 2 weeks
EFPE_SC_6MG_Q2W
5.67 (0.88 to 29.64)0.46 to 45.58Unclear
Efpeglenatide 8 mg injection every 2 weeks
EFPE_SC_8MG_Q2W
5.16 (0.76 to 26.59)0.42 to 38.78Unclear
Efpeglenatide 4 mg subcutaneous once weekly
EFPE_SC_4MG_QW
5.07 (0.75 to 26.15)0.44 to 39.48Unclear
Standard care or no added treatment
STANDARD_CARE
2.34 (0.28 to 13.63)0.17 to 19.88Unclear

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 columnPLACEBOMAZD_SC_6MG_QWMAZD_SC_4p5MG_QWMAZD_SC_16MG_QWLIRA_SC_3p0MG_QDEFPE_SC_6MG_QWMAZD_SC_3MG_QWEXENER_SC_2-10MG_QWEFPE_SC_6MG_Q2WEFPE_SC_8MG_Q2WEFPE_SC_4MG_QWSTANDARD_CARE
PLACEBOPLACEBO0.03
0.00 to 0.27		0.03
0.00 to 0.25		0.06
0.00 to 0.71		0.08
0.02 to 0.40		0.12
0.02 to 0.82		0.13
0.02 to 0.96		0.14
0.01 to 1.96		0.18
0.03 to 1.14		0.19
0.04 to 1.31		0.20
0.04 to 1.34		0.43
0.07 to 3.61
MAZD_SC_6MG_QW34.09
3.72 to 218		MAZD_SC_6MG_QW1.07
0.25 to 4.83		1.89
0.05 to 40.68		2.66
0.23 to 25.71		4.22
0.30 to 49.31		4.24
0.83 to 19.02		4.68
0.10 to 115		6.26
0.45 to 70.82		6.72
0.50 to 72.38		6.87
0.50 to 77.85		14.98
1.06 to 187
MAZD_SC_4p5MG_QW31.82
3.99 to 207		0.94
0.21 to 4.07		MAZD_SC_4p5MG_QW1.78
0.04 to 36.45		2.48
0.23 to 25.27		3.97
0.32 to 45.21		4.01
0.84 to 17.11		4.33
0.10 to 104		5.85
0.46 to 73.11		6.32
0.47 to 72.75		6.39
0.51 to 76.83		14.10
0.97 to 183
MAZD_SC_16MG_QW17.83
1.40 to 409		0.53
0.02 to 21.51		0.56
0.03 to 22.81		MAZD_SC_16MG_QW1.40
0.08 to 48.28		2.19
0.11 to 77.72		2.28
0.11 to 83.38		2.49
0.04 to 138		3.31
0.16 to 110		3.62
0.17 to 132		3.71
0.18 to 135		7.91
0.35 to 334
LIRA_SC_3p0MG_QD13.05
2.47 to 55.36		0.38
0.04 to 4.39		0.40
0.04 to 4.37		0.71
0.02 to 13.15		LIRA_SC_3p0MG_QD1.58
0.18 to 15.26		1.63
0.15 to 16.86		1.79
0.05 to 34.56		2.31
0.27 to 22.33		2.53
0.29 to 26.29		2.61
0.30 to 24.40		5.57
1.38 to 24.21
EFPE_SC_6MG_QW8.25
1.22 to 42.60		0.24
0.02 to 3.28		0.25
0.02 to 3.08		0.46
0.01 to 9.20		0.63
0.07 to 5.62		EFPE_SC_6MG_QW1.01
0.09 to 11.93		1.11
0.03 to 23.79		1.47
0.32 to 6.90		1.61
0.34 to 7.30		1.63
0.35 to 8.08		3.57
0.30 to 43.33
MAZD_SC_3MG_QW8.00
1.04 to 52.62		0.24
0.05 to 1.21		0.25
0.06 to 1.19		0.44
0.01 to 9.48		0.62
0.06 to 6.63		0.99
0.08 to 11.38		MAZD_SC_3MG_QW1.07
0.03 to 25.82		1.45
0.11 to 17.35		1.56
0.12 to 18.80		1.60
0.13 to 19.35		3.52
0.27 to 47.62
EXENER_SC_2-10MG_QW7.23
0.51 to 188		0.21
0.01 to 9.99		0.23
0.01 to 10.04		0.40
0.01 to 23.32		0.56
0.03 to 21.33		0.90
0.04 to 33.96		0.94
0.04 to 37.69		EXENER_SC_2-10MG_QW1.35
0.06 to 53.26		1.44
0.07 to 59.75		1.49
0.06 to 64.46		3.18
0.13 to 140
EFPE_SC_6MG_Q2W5.67
0.88 to 29.64		0.16
0.01 to 2.21		0.17
0.01 to 2.19		0.30
0.01 to 6.07		0.43
0.04 to 3.66		0.68
0.14 to 3.14		0.69
0.06 to 8.78		0.74
0.02 to 17.22		EFPE_SC_6MG_Q2W1.09
0.22 to 5.27		1.11
0.23 to 5.14		2.42
0.21 to 29.41
EFPE_SC_8MG_Q2W5.16
0.76 to 26.59		0.15
0.01 to 2.00		0.16
0.01 to 2.13		0.28
0.01 to 5.99		0.40
0.04 to 3.42		0.62
0.14 to 2.98		0.64
0.05 to 8.09		0.70
0.02 to 15.32		0.92
0.19 to 4.47		EFPE_SC_8MG_Q2W1.03
0.21 to 4.85		2.21
0.18 to 26.34
EFPE_SC_4MG_QW5.07
0.75 to 26.15		0.15
0.01 to 1.99		0.16
0.01 to 1.94		0.27
0.01 to 5.54		0.38
0.04 to 3.36		0.61
0.12 to 2.87		0.62
0.05 to 7.80		0.67
0.02 to 15.96		0.90
0.19 to 4.33		0.97
0.21 to 4.69		EFPE_SC_4MG_QW2.14
0.18 to 27.31
STANDARD_CARE2.34
0.28 to 13.63		0.07
0.01 to 0.94		0.07
0.01 to 1.03		0.13
0.00 to 2.84		0.18
0.04 to 0.73		0.28
0.02 to 3.32		0.28
0.02 to 3.69		0.31
0.01 to 7.75		0.41
0.03 to 4.79		0.45
0.04 to 5.57		0.47
0.04 to 5.56		STANDARD_CARE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.375 (95% CrI 0.076 to 1.810), log scale
Residual deviance
20.5 for 17 data points
DIC
34.0 (pD 13.5)
Largest R-hat
1.002
Smallest ESS
bulk 1,919, tail 1,721
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; 6 of 6
Type 2 diabetes share in weight trials (percent of participants)
effect modifier; 6 of 6
Sex (percent female)
effect modifier, prognostic factor; 6 of 6
Treatment duration (weeks)
effect modifier; 6 of 6
Lifestyle co-intervention intensity (none standard intensive)
effect modifier, prognostic factor; 6 of 6
NCT02075281
S000743
35.440
population codes
76.3520standard
NCT04904913
S001183
31.830
population codes
52.0324none
Dapalost
S001235
35.40
population codes
61.2524standard
NCT05623839
S001559
32.50
population codes
5020none
STRIVE
S001687
45.9635.564.28104intensive
NCT01557166
S002315
39.150
population codes
28.132standard

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 31.8 (MAZD_SC_3MG_QW vs MAZD_SC_4p5MG_QW vs MAZD_SC_6MG_QW vs PLACEBO) to 46.0 (LIRA_SC_3p0MG_QD vs STANDARD_CARE) kg/m2; threshold 3
  • FlagBaseline, Type 2 diabetes share in weight trials: design means range from 0.0 (EFPE_SC_4MG_QW vs EFPE_SC_6MG_Q2W vs EFPE_SC_6MG_QW vs EFPE_SC_8MG_Q2W vs PLACEBO) to 35.5 (LIRA_SC_3p0MG_QD vs STANDARD_CARE) percent of participants; threshold 20
  • FlagBaseline, Sex: design means range from 28.1 (LIRA_SC_3p0MG_QD vs PLACEBO) to 76.3 (EFPE_SC_4MG_QW vs EFPE_SC_6MG_Q2W vs EFPE_SC_6MG_QW vs EFPE_SC_8MG_Q2W vs PLACEBO) percent female; threshold 15
  • FlagBaseline, Treatment duration: design means range from 20.0 (EFPE_SC_4MG_QW vs EFPE_SC_6MG_Q2W vs EFPE_SC_6MG_QW vs EFPE_SC_8MG_Q2W vs PLACEBO) to 104.0 (LIRA_SC_3p0MG_QD vs STANDARD_CARE) weeks; threshold 26
  • NoteOutcome assessment, time point: selected time points span 20 to 32 weeks
  • NoteOutcome assessment, analysis set: mixed: completers 2, full_analysis 3, modified_itt 1
  • NoteOutcome assessment, definition: mixed: body weight reduction of 5 percent or more 1, not stated 4, weight loss of 5% or more 1
  • NoteOutcome assessment, proportion method: mixed: not stated 3, not_stated 3
  • NoteRisk of bias, blinding: mixed: double_blind 5, open_label 1
  • NoteData handling, input conversions: arms_combined 1, count_from_percent 4
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
NCT0207528120full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2014age 18 to 64 years; BMI 30 to 42, or 27 to 30 with comorbidity; FPG below 7 mmol/L; HbA1c 6.5 percent or less; no diabetes
NCT0490491324modified_ittnot statednot statednot statednot statednot statednot stateddouble_blindindustry2021Chinese adults 18 to 75; BMI 28 or more, or 24 or more with comorbidity or hyperphagia; no diabetes, HbA1c below 6.5
Dapalost24full_analysisbody weight reduction of 5 percent or morenot statednot statednot_statednot statednot stateddouble_blindindustry2014age 18 to 70; BMI 30 to 45 kg/m2; no diabetes
NCT0562383927completersnot statednot statednot statednot_statednot statednot stateddouble_blindindustry2022age 18 to 70; BMI 27 to 50; HbA1c below 6.5 percent; no diabetes
STRIVE32completersnot 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
NCT0155716632full_analysisweight loss of 5% or morenot statednot statednot_statednot statednot stateddouble_blindindustry2012age 18 to 64; BMI 30 or more; AHI 15 or more; no diabetes; unable or unwilling to use CPAP

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
NCT02075281A1PLACEBO20arm, responders1 / 60R0011218:Figure 1
NCT02075281A2EFPE_SC_4MG_QW20arm, responders11 / 59R0011218:Figure 1
NCT02075281A3EFPE_SC_6MG_QW20arm, responders16 / 59R0011218:Figure 1
NCT02075281A4EFPE_SC_6MG_Q2W20arm, responders12 / 59R0011218:Figure 1
NCT02075281A5EFPE_SC_8MG_Q2W20arm, responders11 / 58R0011218:Figure 1
NCT04904913A1MAZD_SC_3MG_QW24arm, responders12 / 62R0016107:Table 2
NCT04904913A2MAZD_SC_4p5MG_QW24arm, responders31 / 63R0016107:Table 2
NCT04904913A3MAZD_SC_6MG_QW24arm, responders31 / 61R0016107:Table 2
NCT04904913A4PLACEBO24arm, responders0 / 62R0016107:Table 2
DapalostA1EXENER_SC_2-10MG_QW24arm, responders3 / 25R0025627:Table 2
DapalostA2PLACEBO24arm, responders0 / 24R0025627:Table 2
NCT05623839A1PLACEBO27arm, responders0 / 6count_from_percentR0013210:Figure 2
NCT05623839A2+A3MAZD_SC_16MG_QW27arm, responders13 / 21count_from_percent;arms_combinedR0013210:Figure 2
STRIVEA1STANDARD_CARE32arm, responders14 / 79R0020855:Supplement Table S4
STRIVEA2LIRA_SC_3p0MG_QD32arm, responders110 / 208R0020855:Supplement Table S4
NCT01557166A1LIRA_SC_3p0MG_QD32arm, responders42 / 180count_from_percentR0026203:Results
NCT01557166A2PLACEBO32arm, responders3 / 179count_from_percentR0026203:Results

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