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 40 to 104 (target week 68)Not stated by the trialsEach dose separatelyOdds ratio
5
Randomized trials
11
Treatments
3,426
Participants
1,531
Events

In plain language

Across 5 trials with 3,426 participants, 4 of 10 treatments had a clearly better result than placebo on weight loss of 5 percent or more, and for 6 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 2.0 mg subcutaneous once weekly: odds ratio 8.47 (95% credible interval 1.05 to 29.37).

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.
CANAGLIFLOZINCOTA_SC_100UG_QDCOTA_SC_200UG_QDCOTA_SC_300UG_QDDULA_SC_0p75MG_QWDULA_SC_1p5MG_QWLIRA_SC_1p8MG_QDPLACEBOSEMA_SC_0p5MG_QWSEMA_SC_1p0MG_QWSEMA_SC_2p0MG_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.
0.10.20.250.51245102050← favors referencefavors treatment →Semaglutide 2.0 mg subcutaneous …Semaglutide 1.0 mg subcutaneous …Cotadutide 300 ug subcutaneous o…CanagliflozinCotadutide 100 ug subcutaneous o…Semaglutide 0.5 mg subcutaneous …Cotadutide 200 ug subcutaneous o…Liraglutide 1.8 mg subcutaneous …Dulaglutide 1.5 mg subcutaneous …Dulaglutide 0.75 mg 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
Semaglutide 2.0 mg subcutaneous once weekly
SEMA_SC_2p0MG_QW
8.47 (1.05 to 29.37)0.80 to 36.30Better
Semaglutide 1.0 mg subcutaneous once weekly
SEMA_SC_1p0MG_QW
6.41 (1.34 to 18.73)0.86 to 23.39Better
Cotadutide 300 ug subcutaneous once daily
COTA_SC_300UG_QD
5.59 (1.51 to 14.81)1.05 to 20.68Better
Canagliflozin
CANAGLIFLOZIN
5.01 (0.66 to 17.46)0.46 to 21.07Unclear
Cotadutide 100 ug subcutaneous once daily
COTA_SC_100UG_QD
4.21 (1.18 to 11.53)0.73 to 16.56Better
Semaglutide 0.5 mg subcutaneous once weekly
SEMA_SC_0p5MG_QW
2.91 (0.44 to 10.05)0.31 to 12.35Unclear
Cotadutide 200 ug subcutaneous once daily
COTA_SC_200UG_QD
2.71 (0.74 to 7.28)0.51 to 10.32Unclear
Liraglutide 1.8 mg subcutaneous once daily
LIRA_SC_1p8MG_QD
2.44 (0.71 to 5.97)0.44 to 8.32Unclear
Dulaglutide 1.5 mg subcutaneous once weekly
DULA_SC_1p5MG_QW
1.62 (0.25 to 5.80)0.18 to 7.06Unclear
Dulaglutide 0.75 mg subcutaneous once weekly
DULA_SC_0p75MG_QW
1.12 (0.18 to 3.94)0.13 to 4.78Unclear

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 columnPLACEBOSEMA_SC_2p0MG_QWSEMA_SC_1p0MG_QWCOTA_SC_300UG_QDCANAGLIFLOZINCOTA_SC_100UG_QDSEMA_SC_0p5MG_QWCOTA_SC_200UG_QDLIRA_SC_1p8MG_QDDULA_SC_1p5MG_QWDULA_SC_0p75MG_QW
PLACEBOPLACEBO0.12
0.03 to 0.95		0.16
0.05 to 0.75		0.18
0.07 to 0.66		0.20
0.06 to 1.51		0.24
0.09 to 0.85		0.34
0.10 to 2.29		0.37
0.14 to 1.35		0.41
0.17 to 1.41		0.62
0.17 to 4.01		0.90
0.25 to 5.67
SEMA_SC_2p0MG_QW8.47
1.05 to 29.37		SEMA_SC_2p0MG_QW1.32
0.43 to 3.34		1.55
0.20 to 5.96		1.71
0.42 to 6.68		2.04
0.28 to 7.92		2.93
0.67 to 10.61		3.18
0.44 to 12.09		3.52
0.67 to 10.74		5.30
1.13 to 19.23		7.72
1.56 to 29.26
SEMA_SC_1p0MG_QW6.41
1.34 to 18.73		0.76
0.30 to 2.34		SEMA_SC_1p0MG_QW1.17
0.25 to 3.80		1.31
0.52 to 3.79		1.54
0.32 to 4.96		2.23
0.82 to 5.94		2.42
0.47 to 7.73		2.65
0.86 to 6.25		4.00
1.49 to 10.67		5.84
2.05 to 15.49
COTA_SC_300UG_QD5.59
1.51 to 14.81		0.65
0.17 to 4.88		0.85
0.26 to 3.98		COTA_SC_300UG_QD1.11
0.28 to 7.56		1.32
0.43 to 4.10		1.88
0.47 to 11.84		2.06
0.67 to 6.00		2.27
0.84 to 7.15		3.39
0.85 to 20.74		4.95
1.20 to 28.73
CANAGLIFLOZIN5.01
0.66 to 17.46		0.58
0.15 to 2.38		0.77
0.26 to 1.91		0.90
0.13 to 3.53		CANAGLIFLOZIN1.19
0.16 to 4.72		1.70
0.40 to 6.40		1.86
0.24 to 7.36		2.05
0.39 to 6.44		3.07
0.69 to 11.03		4.50
0.97 to 15.92
COTA_SC_100UG_QD4.21
1.18 to 11.53		0.49
0.13 to 3.51		0.65
0.20 to 3.17		0.76
0.24 to 2.32		0.84
0.21 to 6.06		COTA_SC_100UG_QD1.43
0.36 to 9.70		1.56
0.48 to 4.66		1.72
0.61 to 5.67		2.58
0.64 to 17.01		3.77
0.90 to 22.98
SEMA_SC_0p5MG_QW2.91
0.44 to 10.05		0.34
0.09 to 1.49		0.45
0.17 to 1.23		0.53
0.08 to 2.13		0.59
0.16 to 2.48		0.70
0.10 to 2.80		SEMA_SC_0p5MG_QW1.09
0.17 to 4.26		1.20
0.27 to 3.91		1.81
0.62 to 4.99		2.63
0.89 to 6.83
COTA_SC_200UG_QD2.71
0.74 to 7.28		0.31
0.08 to 2.25		0.41
0.13 to 2.14		0.49
0.17 to 1.48		0.54
0.14 to 4.23		0.64
0.21 to 2.07		0.92
0.23 to 5.84		COTA_SC_200UG_QD1.09
0.41 to 3.48		1.66
0.42 to 10.52		2.42
0.58 to 14.72
LIRA_SC_1p8MG_QD2.44
0.71 to 5.97		0.28
0.09 to 1.49		0.38
0.16 to 1.16		0.44
0.14 to 1.19		0.49
0.16 to 2.59		0.58
0.18 to 1.63		0.84
0.26 to 3.76		0.92
0.29 to 2.42		LIRA_SC_1p8MG_QD1.52
0.46 to 6.92		2.20
0.64 to 9.13
DULA_SC_1p5MG_QW1.62
0.25 to 5.80		0.19
0.05 to 0.89		0.25
0.09 to 0.67		0.29
0.05 to 1.18		0.33
0.09 to 1.46		0.39
0.06 to 1.57		0.55
0.20 to 1.62		0.60
0.10 to 2.36		0.66
0.14 to 2.15		DULA_SC_1p5MG_QW1.46
0.50 to 4.12
DULA_SC_0p75MG_QW1.12
0.18 to 3.94		0.13
0.03 to 0.64		0.17
0.06 to 0.49		0.20
0.03 to 0.83		0.22
0.06 to 1.03		0.27
0.04 to 1.11		0.38
0.15 to 1.12		0.41
0.07 to 1.73		0.45
0.11 to 1.56		0.69
0.24 to 1.99		DULA_SC_0p75MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.316 (95% CrI 0.066 to 1.148), log scale
Residual deviance
14.4 for 14 data points
DIC
28.2 (pD 13.7)
Largest R-hat
1.001
Smallest ESS
bulk 1,507, tail 2,030
Divergent transitions
0
Convergence
All criteria met
Priors
PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2.53, 1.58^2) on tau^2 (General physical health indicators, pharm vs pharm)

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; 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 7
S000372
33.555.1240not_reported
SUSTAIN FORTE
S001353
34.641.4240not_reported
SUSTAIN 8
S001847
not reported46.1952not_reported
S003432
S003432
34.4556.8552not_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 2 of 5 trials
  • FlagBaseline, Sex: design means range from 41.4 (SEMA_SC_1p0MG_QW vs SEMA_SC_2p0MG_QW) to 56.8 (LIRA_SC_1p8MG_QD vs SEMA_SC_1p0MG_QW) percent female; threshold 15
  • NoteOutcome assessment, time point: selected time points span 40 to 54 weeks
  • NoteOutcome assessment, analysis set: mixed: full_analysis 3, other 1, per_protocol 1
  • NoteOutcome assessment, proportion method: mixed: not stated 2, not_stated 3
  • NoteRisk of bias, blinding: mixed: double_blind 3, open_label 2
  • NoteRisk of bias, funding: mixed: industry 4, non_industry 1
  • NoteData handling, input conversions: count_from_percent 8
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
NCT0323505054per_protocolnot statednot statednot statednot statednot statednot stateddouble_blindindustry2017age 18 or older; BMI 25 or higher; HbA1c 7.0 to 10.5 percent; on metformin
SUSTAIN 740full_analysisnot statednot statednot statednot_statednot statednot statedopen_labelindustry2016age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin background
SUSTAIN FORTE40full_analysisnot statednot statednot statednot_statednot statednot stateddouble_blindindustry2019T2D on metformin with or without SU; HbA1c 8.0 to 10.0 percent; duration at least 6 months
SUSTAIN 852full_analysisnot statednot statednot statednot_statednot statednot stateddouble_blindindustry2017age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin 1500 mg or maximum tolerated
S00343252othernot statednot statednot statednot statednot statednot statedopen_labelnon_industry2020age 18 to 65; type 2 diabetes 1 year or more; HbA1c 7.0 to 10.5 percent; BMI 30 or higher; stable metformin

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
NCT03235050A1PLACEBO54arm, responders9 / 91R0016374:Results
NCT03235050A2LIRA_SC_1p8MG_QD54arm, responders32 / 104R0016374:Results
NCT03235050A3COTA_SC_100UG_QD54arm, responders30 / 75R0016374:Results
NCT03235050A4COTA_SC_200UG_QD54arm, responders59 / 199R0016374:Results
NCT03235050A5COTA_SC_300UG_QD54arm, responders87 / 187R0016374:Results
SUSTAIN 7A1SEMA_SC_0p5MG_QW40arm, responders132 / 301count_from_percentregistry:outcomes
SUSTAIN 7A2SEMA_SC_1p0MG_QW40arm, responders189 / 300count_from_percentregistry:outcomes
SUSTAIN 7A3DULA_SC_0p75MG_QW40arm, responders68 / 299count_from_percentregistry:outcomes
SUSTAIN 7A4DULA_SC_1p5MG_QW40arm, responders90 / 298count_from_percentregistry:outcomes
SUSTAIN FORTEA1SEMA_SC_1p0MG_QW40arm, responders247 / 481count_from_percentregistry:outcomes
SUSTAIN FORTEA2SEMA_SC_2p0MG_QW40arm, responders284 / 480count_from_percentregistry:outcomes
SUSTAIN 8A1SEMA_SC_1p0MG_QW52arm, responders157 / 298count_from_percentregistry:outcomes
SUSTAIN 8A2CANAGLIFLOZIN52arm, responders147 / 313count_from_percentregistry:outcomes
S003432A1SEMA_SC_1p0MG_QW52contrast, or1.2350.290R0053844:Table 1
S003432A2LIRA_SC_1p8MG_QD52contrast, orR0053844:Table 1

Rerun this analysis yourself

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