LivingGLP1
Network meta-analysis

Weight loss of 5 percent or more

Type 2 diabetes (adults); background therapy: one or more non insulin glucose lowering drugs

weeks 20 to 40 (target week 26)Not stated by the trialsEach dose separatelyOdds ratio
5
Randomized trials
9
Treatments
2,126
Participants
689
Events

In plain language

Across 5 trials with 2,126 participants, 5 of 8 treatments had a clearly better result than placebo on weight loss of 5 percent or more, and for 3 the evidence could not tell them apart from placebo. The most favorable estimate was for Polyethylene glycol loxenatide 400 µg injection once weekly: odds ratio 19.62 (95% credible interval 3.03 to 176).

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.
COTA_SC_100UG_QDCOTA_SC_200UG_QDCOTA_SC_300UG_QDLIRA_SC_1p2MG_QDLIXI_SC_20UG_QDPEGLOX_SC_300UG_QWPEGLOX_SC_400UG_QWPLACEBOSEMA_SC_1p0MG_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

Odds ratio. Higher values favor the treatment.
0.20.250.51245102050100← favors referencefavors treatment →Polyethylene glycol loxenatide 4…Semaglutide 1.0 mg subcutaneous …Polyethylene glycol loxenatide 3…Cotadutide 300 ug subcutaneous o…Cotadutide 200 ug subcutaneous o…Cotadutide 100 ug subcutaneous o…Liraglutide 1.2 mg subcutaneous …Lixisenatide 20 ug subcutaneous …
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
Polyethylene glycol loxenatide 400 µg injection once weekly
PEGLOX_SC_400UG_QW
19.62 (3.03 to 176)2.46 to 21228.63 (3.52 to 233)Better
Semaglutide 1.0 mg subcutaneous once weekly
SEMA_SC_1p0MG_QW
10.67 (2.99 to 29.84)2.00 to 40.6812.00 (5.74 to 25.08)Better
Polyethylene glycol loxenatide 300 µg injection once weekly
PEGLOX_SC_300UG_QW
7.22 (1.47 to 37.35)1.04 to 46.598.98 (2.31 to 34.91)Better
Cotadutide 300 ug subcutaneous once daily
COTA_SC_300UG_QD
6.22 (1.85 to 16.82)1.21 to 23.666.92 (3.54 to 13.51)Better
Cotadutide 200 ug subcutaneous once daily
COTA_SC_200UG_QD
3.52 (1.00 to 9.40)0.68 to 13.323.88 (1.97 to 7.63)Better
Cotadutide 100 ug subcutaneous once daily
COTA_SC_100UG_QD
3.18 (0.91 to 9.04)0.62 to 12.313.57 (1.67 to 7.64)Unclear
Liraglutide 1.2 mg subcutaneous once daily
LIRA_SC_1p2MG_QD
1.78 (0.37 to 6.62)0.26 to 8.842.05 (0.89 to 4.70)Unclear
Lixisenatide 20 ug subcutaneous once daily
LIXI_SC_20UG_QD
1.61 (0.55 to 4.57)0.36 to 6.611.64 (0.99 to 2.72)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 columnPLACEBOPEGLOX_SC_400UG_QWSEMA_SC_1p0MG_QWPEGLOX_SC_300UG_QWCOTA_SC_300UG_QDCOTA_SC_200UG_QDCOTA_SC_100UG_QDLIRA_SC_1p2MG_QDLIXI_SC_20UG_QD
PLACEBOPLACEBO0.05
0.01 to 0.33		0.09
0.03 to 0.33		0.14
0.03 to 0.68		0.16
0.06 to 0.54		0.28
0.11 to 1.00		0.31
0.11 to 1.10		0.56
0.15 to 2.72		0.62
0.22 to 1.83
PEGLOX_SC_400UG_QW19.62
3.03 to 176		PEGLOX_SC_400UG_QW1.89
0.23 to 20.86		2.68
0.34 to 30.75		3.24
0.40 to 38.34		5.68
0.74 to 65.47		6.30
0.77 to 74.72		11.36
1.16 to 154		12.29
1.45 to 138
SEMA_SC_1p0MG_QW10.67
2.99 to 29.84		0.53
0.05 to 4.34		SEMA_SC_1p0MG_QW1.45
0.18 to 9.32		1.71
0.33 to 8.09		3.05
0.62 to 13.95		3.33
0.69 to 16.50		6.00
2.25 to 16.32		6.62
1.24 to 30.06
PEGLOX_SC_300UG_QW7.22
1.47 to 37.35		0.37
0.03 to 2.97		0.69
0.11 to 5.48		PEGLOX_SC_300UG_QW1.16
0.19 to 8.43		2.08
0.34 to 15.09		2.27
0.36 to 17.32		4.14
0.55 to 38.25		4.50
0.68 to 30.50
COTA_SC_300UG_QD6.22
1.85 to 16.82		0.31
0.03 to 2.48		0.58
0.12 to 2.99		0.86
0.12 to 5.38		COTA_SC_300UG_QD1.78
0.65 to 4.79		1.96
0.67 to 5.50		3.53
0.60 to 21.87		3.87
0.72 to 16.00
COTA_SC_200UG_QD3.52
1.00 to 9.40		0.18
0.02 to 1.36		0.33
0.07 to 1.61		0.48
0.07 to 2.93		0.56
0.21 to 1.54		COTA_SC_200UG_QD1.09
0.38 to 3.27		1.96
0.34 to 12.02		2.20
0.42 to 8.75
COTA_SC_100UG_QD3.18
0.91 to 9.04		0.16
0.01 to 1.30		0.30
0.06 to 1.45		0.44
0.06 to 2.77		0.51
0.18 to 1.50		0.91
0.31 to 2.64		COTA_SC_100UG_QD1.79
0.30 to 10.87		1.97
0.38 to 8.93
LIRA_SC_1p2MG_QD1.78
0.37 to 6.62		0.09
0.01 to 0.86		0.17
0.06 to 0.44		0.24
0.03 to 1.83		0.28
0.05 to 1.67		0.51
0.08 to 2.90		0.56
0.09 to 3.31		LIRA_SC_1p2MG_QD1.10
0.16 to 6.08
LIXI_SC_20UG_QD1.61
0.55 to 4.57		0.08
0.01 to 0.69		0.15
0.03 to 0.80		0.22
0.03 to 1.46		0.26
0.06 to 1.39		0.45
0.11 to 2.36		0.51
0.11 to 2.60		0.91
0.16 to 6.45		LIXI_SC_20UG_QD

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.304 (95% CrI 0.075 to 1.172), log scale
Residual deviance
12.8 for 13 data points
DIC
25.2 (pD 12.4)
Largest R-hat
1.001
Smallest ESS
bulk 2,952, tail 2,634
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
Q (total)
0.00 on 0 df
Q (between designs)
0.00

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; 3 of 5
Sex (percent female)
effect modifier, prognostic factor; 5 of 5
Treatment duration (weeks)
effect modifier; 5 of 5
Lifestyle co-intervention intensity (none standard intensive)
effect modifier, prognostic factor; 5 of 5
NCT03235050
S000257
not reported53.7254not_reported
SUSTAIN 9
S000483
31.941.7230not_reported
SUSTAIN 10
S000584
body weight 96.9 kg
43.3330not_reported
GETGOAL-F1
S001563
32.5355.5924not_reported
S002928
S002928
53.83
median
32.3724standard

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 2 of 5 trials
  • FlagBaseline, Baseline BMI or body weight: design means range from 31.9 (PLACEBO vs SEMA_SC_1p0MG_QW) to 53.8 (PEGLOX_SC_300UG_QW vs PEGLOX_SC_400UG_QW vs PLACEBO) kg/m2; threshold 3
  • FlagBaseline, Sex: design means range from 32.4 (PEGLOX_SC_300UG_QW vs PEGLOX_SC_400UG_QW vs PLACEBO) to 55.6 (LIXI_SC_20UG_QD vs PLACEBO) percent female; threshold 15
  • FlagBaseline, Treatment duration: design means range from 24.0 (LIXI_SC_20UG_QD vs PLACEBO) to 54.0 (COTA_SC_100UG_QD vs COTA_SC_200UG_QD vs COTA_SC_300UG_QD vs PLACEBO) weeks; threshold 26
  • NoteOutcome assessment, time point: selected time points span 24 to 30 weeks
  • NoteOutcome assessment, analysis set: mixed: completers 1, full_analysis 3, modified_itt 1
  • NoteOutcome assessment, definition: mixed: HbA1c below 7 percent at week 24 1, not stated 4
  • NoteOutcome assessment, proportion method: mixed: not stated 1, not_stated 3, observed 1
  • NoteRisk of bias, blinding: mixed: double_blind 3, open_label 1, single_blind 1
  • NoteRisk of bias, funding: mixed: industry 4, non_industry 1
  • NoteData handling, input conversions: arms_combined 1, count_from_percent 9
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
NCT0323505026full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2017age 18 or older; BMI 25 or higher; HbA1c 7.0 to 10.5 percent; on metformin
SUSTAIN 930full_analysisnot statednot statednot statedobservednot statednot stateddouble_blindindustry2017adults 18 or older (20 in Japan); HbA1c 7.0 to 10.5 percent; stable SGLT2i with or without metformin or SU
SUSTAIN 1030full_analysisnot statednot statednot statednot_statednot statednot statedopen_labelindustry2017adults with T2D, HbA1c 7.0 to 11.0 percent on 1 to 3 oral drugs
GETGOAL-F124modified_ittnot statednot statednot statednot_statednot statednot stateddouble_blindindustry2008adults with T2D on metformin
S00292824completersHbA1c below 7 percent at week 24not statednot statednot_statednot statednot statedsingle_blindnon_industry2022age 18 to 65; BMI 50 or more; type 2 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 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
NCT03235050A1PLACEBO26arm, responders11 / 112registry:outcomes
NCT03235050A3COTA_SC_100UG_QD26arm, responders28 / 100registry:outcomes
NCT03235050A4COTA_SC_200UG_QD26arm, responders76 / 256registry:outcomes
NCT03235050A5COTA_SC_300UG_QD26arm, responders110 / 256registry:outcomes
SUSTAIN 9A1SEMA_SC_1p0MG_QW30arm, responders61 / 121count_from_percentregistry:outcomes
SUSTAIN 9A2PLACEBO30arm, responders10 / 128count_from_percentregistry:outcomes
SUSTAIN 10A1SEMA_SC_1p0MG_QW30arm, responders162 / 290count_from_percentregistry:outcomes
SUSTAIN 10A2LIRA_SC_1p2MG_QD30arm, responders51 / 287count_from_percentregistry:outcomes
GETGOAL-F1A1PLACEBO24arm, responders24 / 158count_from_percentregistry:outcomes
GETGOAL-F1A2+A3LIXI_SC_20UG_QD24arm, responders71 / 313count_from_percent;arms_combinedregistry:outcomes
S002928A1PLACEBO24arm, responders19 / 35count_from_percentR0007034:Results
S002928A2PEGLOX_SC_300UG_QW24arm, responders32 / 35count_from_percentR0007034:Results
S002928A3PEGLOX_SC_400UG_QW24arm, responders34 / 35count_from_percentR0007034:Results

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