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 trialsDoses of a drug pooledOdds ratio
6
Randomized trials
7
Treatments
2,126
Participants
689
Events

In plain language

Across 6 trials with 2,126 participants, 3 of 6 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 injection: odds ratio 12.20 (95% credible interval 2.82 to 49.50).

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_SCLIRA_SCLIXI_SCPEGLOX_SCPLACEBOSEMA_SCSITAGLIPTIN
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.
0.050.10.20.250.51245102050ā† favors referencefavors treatment ā†’Polyethylene glycol loxenatide iā€¦Semaglutide injectionCotadutide injectionLiraglutide injectionLixisenatide injectionSitagliptin
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 injection
PEGLOX_SC
12.20 (2.82 to 49.50)1.99 to 62.6713.89 (4.15 to 46.53)Better
Semaglutide injection
SEMA_SC
10.93 (3.32 to 29.03)2.39 to 40.9912.00 (5.74 to 25.08)Better
Cotadutide injection
COTA_SC
4.74 (1.48 to 13.64)1.06 to 18.934.94 (2.59 to 9.40)Better
Liraglutide injection
LIRA_SC
1.86 (0.46 to 6.41)0.33 to 8.532.05 (0.89 to 4.70)Unclear
Lixisenatide injection
LIXI_SC
1.63 (0.59 to 4.47)0.39 to 6.691.64 (0.99 to 2.72)Unclear
Sitagliptin
SITAGLIPTIN
0.43 (0.08 to 2.05)0.06 to 2.58Unclear

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_SCSEMA_SCCOTA_SCLIRA_SCLIXI_SCSITAGLIPTIN
PLACEBOPLACEBO0.08
0.02 to 0.35		0.09
0.03 to 0.30		0.21
0.07 to 0.67		0.54
0.16 to 2.20		0.61
0.22 to 1.71		2.34
0.49 to 11.81
PEGLOX_SC12.20
2.82 to 49.50		PEGLOX_SC1.13
0.20 to 6.52		2.58
0.40 to 15.31		6.67
0.91 to 44.92		7.61
1.18 to 40.70		28.92
2.87 to 229
SEMA_SC10.93
3.32 to 29.03		0.89
0.15 to 5.11		SEMA_SC2.28
0.48 to 9.84		5.87
2.19 to 15.24		6.72
1.45 to 27.07		25.72
6.04 to 98.25
COTA_SC4.74
1.48 to 13.64		0.39
0.07 to 2.52		0.44
0.10 to 2.08		COTA_SC2.57
0.48 to 14.31		2.94
0.64 to 12.70		11.11
1.69 to 76.31
LIRA_SC1.86
0.46 to 6.41		0.15
0.02 to 1.10		0.17
0.07 to 0.46		0.39
0.07 to 2.07		LIRA_SC1.16
0.21 to 5.71		4.37
1.52 to 11.35
LIXI_SC1.63
0.59 to 4.47		0.13
0.02 to 0.85		0.15
0.04 to 0.69		0.34
0.08 to 1.57		0.86
0.18 to 4.71		LIXI_SC3.81
0.60 to 25.78
SITAGLIPTIN0.43
0.08 to 2.05		0.03
0.00 to 0.35		0.04
0.01 to 0.17		0.09
0.01 to 0.59		0.23
0.09 to 0.66		0.26
0.04 to 1.67		SITAGLIPTIN

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.294 (95% CrI 0.068 to 1.139), log scale
Residual deviance
10.9 for 11 data points
DIC
21.6 (pD 10.8)
Largest R-hat
1.001
Smallest ESS
bulk 3,128, tail 2,580
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; 4 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
NCT03235050
S000257
not reported53.7254not_reported
SUSTAIN 9
S000483
31.941.7230not_reported
SUSTAIN 10
S000584
body weight 96.9 kg
43.3330not_reported
NCT02008682
S000650
27.2540.3526not_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 6 trials
  • FlagBaseline, Baseline BMI or body weight: design means range from 27.2 (LIRA_SC vs SITAGLIPTIN) to 53.8 (PEGLOX_SC vs PLACEBO) kg/m2; threshold 3
  • FlagBaseline, Sex: design means range from 32.4 (PEGLOX_SC vs PLACEBO) to 55.6 (LIXI_SC vs PLACEBO) percent female; threshold 15
  • FlagBaseline, Treatment duration: design means range from 24.0 (LIXI_SC vs PLACEBO) to 54.0 (COTA_SC 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 4, modified_itt 1
  • NoteOutcome assessment, definition: mixed: HbA1c below 7 percent at week 24 1, not stated 5
  • NoteOutcome assessment, proportion method: mixed: not stated 2, not_stated 3, observed 1
  • NoteRisk of bias, blinding: mixed: double_blind 3, open_label 2, single_blind 1
  • NoteRisk of bias, funding: mixed: industry 5, non_industry 1
  • NoteData handling, input conversions: arms_combined 3, count_from_percent 8
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
NCT0200868226full_analysisnot statednot statednot statednot statednot statednot statedopen_labelindustry2013Chinese adults 18 to 80; HbA1c 7.0 to 10.0 on metformin; BMI 45 or lower
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
NCT03235050A3+A4+A5COTA_SC26arm, responders214 / 612arms_combinedregistry:outcomes
SUSTAIN 9A1SEMA_SC30arm, responders61 / 121count_from_percentregistry:outcomes
SUSTAIN 9A2PLACEBO30arm, responders10 / 128count_from_percentregistry:outcomes
SUSTAIN 10A1SEMA_SC30arm, responders162 / 290count_from_percentregistry:outcomes
SUSTAIN 10A2LIRA_SC30arm, responders51 / 287count_from_percentregistry:outcomes
NCT02008682A1LIRA_SC26contrast, or1.5040.264R0025836:Figure 3
NCT02008682A2SITAGLIPTIN26contrast, orR0025836:Figure 3
GETGOAL-F1A1PLACEBO24arm, responders24 / 158count_from_percentregistry:outcomes
GETGOAL-F1A2+A3LIXI_SC24arm, responders71 / 313count_from_percent;arms_combinedregistry:outcomes
S002928A1PLACEBO24arm, responders19 / 35count_from_percentR0007034:Results
S002928A2+A3PEGLOX_SC24arm, responders66 / 70count_from_percent;arms_combinedR0007034:Results

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