LivingGLP1
Network meta-analysis

HbA1c below 7 percent

Type 2 diabetes (adults); background therapy: no glucose lowering drug (lifestyle only)

weeks 36 to 64 (target week 52)Not stated by the trialsEach dose separatelyOdds ratio
4
Randomized trials
11
Treatments
1,443
Participants
796
Events

In plain language

Across 4 trials with 1,443 participants, 2 of 10 treatments had a clearly better result than placebo on HbA1c below 7 percent, and for 8 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 14 mg oral once daily (original tablet): odds ratio 13.00 (95% credible interval 2.23 to 46.88).

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.
ALBI_SC_30MG_QWALBI_SC_50MG_QWDULA_SC_0p75MG_QWEFPE_SC_2MG_QWEFPE_SC_4MG_QWEFPE_SC_6MG_QWLIRA_SC_0p9MG_QDPLACEBOSEMA_PO_14MG_QDSEMA_PO_3MG_QDSEMA_PO_7MG_QD
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 →Semaglutide 14 mg oral once dail…Semaglutide 7 mg oral once daily…Dulaglutide 0.75 mg subcutaneous…Albiglutide 50 mg subcutaneous o…Efpeglenatide 4 mg subcutaneous …Efpeglenatide 6 mg subcutaneous …Semaglutide 3 mg oral once daily…Liraglutide 0.9 mg injection onc…Efpeglenatide 2 mg subcutaneous …Albiglutide 30 mg subcutaneous o…
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 14 mg oral once daily (original tablet)
SEMA_PO_14MG_QD
13.00 (2.23 to 46.88)1.31 to 66.8324.75 (7.52 to 81.43)Better
Semaglutide 7 mg oral once daily (original tablet)
SEMA_PO_7MG_QD
8.60 (1.55 to 30.22)0.89 to 45.7216.31 (5.06 to 52.59)Better
Dulaglutide 0.75 mg subcutaneous once weekly
DULA_SC_0p75MG_QW
5.03 (0.59 to 21.59)0.34 to 31.0511.17 (3.21 to 38.89)Unclear
Albiglutide 50 mg subcutaneous once weekly
ALBI_SC_50MG_QW
4.00 (0.49 to 17.14)0.31 to 23.269.11 (2.51 to 33.10)Unclear
Efpeglenatide 4 mg subcutaneous once weekly
EFPE_SC_4MG_QW
3.87 (0.96 to 11.38)0.50 to 19.384.38 (2.40 to 8.02)Unclear
Efpeglenatide 6 mg subcutaneous once weekly
EFPE_SC_6MG_QW
3.86 (0.82 to 11.49)0.45 to 19.694.36 (2.39 to 7.95)Unclear
Semaglutide 3 mg oral once daily (original tablet)
SEMA_PO_3MG_QD
3.80 (0.71 to 13.36)0.42 to 20.047.13 (2.20 to 23.03)Unclear
Liraglutide 0.9 mg injection once daily
LIRA_SC_0p9MG_QD
3.80 (0.77 to 12.07)0.41 to 18.358.04 (2.49 to 25.96)Unclear
Efpeglenatide 2 mg subcutaneous once weekly
EFPE_SC_2MG_QW
3.41 (0.76 to 10.09)0.44 to 17.173.82 (2.09 to 6.97)Unclear
Albiglutide 30 mg subcutaneous once weekly
ALBI_SC_30MG_QW
2.94 (0.34 to 12.47)0.20 to 16.806.66 (1.84 to 24.03)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 columnPLACEBOSEMA_PO_14MG_QDSEMA_PO_7MG_QDDULA_SC_0p75MG_QWALBI_SC_50MG_QWEFPE_SC_4MG_QWEFPE_SC_6MG_QWSEMA_PO_3MG_QDLIRA_SC_0p9MG_QDEFPE_SC_2MG_QWALBI_SC_30MG_QW
PLACEBOPLACEBO0.08
0.02 to 0.45		0.12
0.03 to 0.65		0.20
0.05 to 1.70		0.25
0.06 to 2.06		0.26
0.09 to 1.05		0.26
0.09 to 1.21		0.26
0.07 to 1.40		0.26
0.08 to 1.29		0.29
0.10 to 1.31		0.34
0.08 to 2.97
SEMA_PO_14MG_QD13.00
2.23 to 46.88		SEMA_PO_14MG_QD1.51
0.35 to 6.91		2.56
0.48 to 16.77		3.23
0.60 to 23.60		3.41
0.44 to 18.99		3.41
0.45 to 21.02		3.42
0.79 to 13.96		3.36
0.86 to 14.08		3.90
0.50 to 23.17		4.43
0.73 to 31.79
SEMA_PO_7MG_QD8.60
1.55 to 30.22		0.66
0.14 to 2.87		SEMA_PO_7MG_QD1.71
0.29 to 11.63		2.15
0.38 to 15.82		2.23
0.30 to 12.81		2.28
0.30 to 13.76		2.28
0.51 to 8.93		2.25
0.57 to 9.49		2.58
0.33 to 15.13		2.90
0.50 to 21.16
DULA_SC_0p75MG_QW5.03
0.59 to 21.59		0.39
0.06 to 2.06		0.58
0.09 to 3.47		DULA_SC_0p75MG_QW1.26
0.22 to 7.63		1.32
0.12 to 8.50		1.31
0.13 to 9.44		1.33
0.19 to 7.10		1.32
0.33 to 4.20		1.49
0.14 to 9.75		1.71
0.30 to 10.84
ALBI_SC_50MG_QW4.00
0.49 to 17.14		0.31
0.04 to 1.66		0.46
0.06 to 2.65		0.80
0.13 to 4.52		ALBI_SC_50MG_QW1.04
0.10 to 6.76		1.05
0.11 to 6.77		1.05
0.15 to 5.80		1.04
0.26 to 3.54		1.20
0.12 to 7.62		1.36
0.36 to 5.04
EFPE_SC_4MG_QW3.87
0.96 to 11.38		0.29
0.05 to 2.26		0.45
0.08 to 3.30		0.76
0.12 to 8.39		0.97
0.15 to 9.63		EFPE_SC_4MG_QW1.01
0.27 to 4.01		1.01
0.18 to 7.09		1.01
0.20 to 6.66		1.15
0.30 to 4.54		1.30
0.21 to 13.40
EFPE_SC_6MG_QW3.86
0.82 to 11.49		0.29
0.05 to 2.22		0.44
0.07 to 3.33		0.76
0.11 to 7.99		0.95
0.15 to 8.92		0.99
0.25 to 3.70		EFPE_SC_6MG_QW1.01
0.17 to 7.18		0.99
0.19 to 6.42		1.14
0.28 to 4.42		1.29
0.20 to 13.55
SEMA_PO_3MG_QD3.80
0.71 to 13.36		0.29
0.07 to 1.27		0.44
0.11 to 1.96		0.75
0.14 to 5.21		0.95
0.17 to 6.59		0.99
0.14 to 5.52		0.99
0.14 to 5.79		SEMA_PO_3MG_QD0.99
0.27 to 4.12		1.14
0.15 to 6.59		1.30
0.24 to 8.83
LIRA_SC_0p9MG_QD3.80
0.77 to 12.07		0.30
0.07 to 1.16		0.44
0.11 to 1.76		0.76
0.24 to 3.02		0.96
0.28 to 3.87		0.99
0.15 to 4.99		1.01
0.16 to 5.36		1.01
0.24 to 3.72		LIRA_SC_0p9MG_QD1.15
0.17 to 5.85		1.31
0.37 to 5.48
EFPE_SC_2MG_QW3.41
0.76 to 10.09		0.26
0.04 to 1.99		0.39
0.07 to 3.02		0.67
0.10 to 7.27		0.84
0.13 to 8.44		0.87
0.22 to 3.37		0.88
0.23 to 3.56		0.88
0.15 to 6.51		0.87
0.17 to 5.83		EFPE_SC_2MG_QW1.15
0.17 to 11.95
ALBI_SC_30MG_QW2.94
0.34 to 12.47		0.23
0.03 to 1.37		0.35
0.05 to 1.99		0.59
0.09 to 3.32		0.74
0.20 to 2.81		0.77
0.07 to 4.86		0.77
0.07 to 4.97		0.77
0.11 to 4.24		0.77
0.18 to 2.69		0.87
0.08 to 5.80		ALBI_SC_30MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.394 (95% CrI 0.080 to 1.446), log scale
Residual deviance
14.4 for 14 data points
DIC
27.8 (pD 13.5)
Largest R-hat
1.002
Smallest ESS
bulk 2,005, tail 2,442
Divergent transitions
0
Convergence
All criteria met
Priors
PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2, 1.58^2) on tau^2 (Biological markers (dichotomised), pharm vs pharm)

Frequentist check (netmeta)

Method
inverse variance, REML, OR
Tau
0.000
I squared
0%
Q (total)
0.00 on 1.77635683940025e-15 df, P = 0.000
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 HbA1c (percent)
effect modifier, prognostic factor; 4 of 4
Background glucose lowering therapy (stratum S0 to S4)
effect modifier, prognostic factor; 4 of 4
Diabetes duration (years)
effect modifier, prognostic factor; 4 of 4
NCT01558271
S000837
8.14S06.59
NCT01733758
S001075
8.11S06.65
PIONEER 9
S001943
8.2S07.6
AMPLITUDE-M
S002081
8.07S05.1

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 52 to 56 weeks
  • NoteOutcome assessment, analysis set: mixed: completers 1, full_analysis 2, randomized 1
  • NoteOutcome assessment, definition: mixed: HbA1c below 7.0 percent 1, not stated 3
  • NoteOutcome assessment, proportion method: mixed: not stated 3, not_stated 1
  • NoteData handling, input conversions: count_from_percent 4
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
NCT0155827152full_analysisHbA1c below 7.0 percentnot statednot statednot statednot statednot stateddouble_blindindustry2012Japanese; age 20 or more; BMI 18.5 to 35; HbA1c 7.0 to 10.0 percent; OAM naive or OAM stopped
NCT0173375852completersnot statednot statednot statednot statednot statednot stateddouble_blindindustry2013Japanese adults; diet and exercise with or without one oral drug; HbA1c 7 to 10 percent after washout
PIONEER 952full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2017Japanese adults 20 y or older; HbA1c 6.5 to 9.5 on one oral drug washed out, or 7.0 to 10.0 on diet and exercise
AMPLITUDE-M56randomizednot statednot statednot statednot_statednot statednot stateddouble_blindindustry2017type 2 diabetes on diet and exercise, HbA1c 7 to 10 percent, no glucose lowering drug in prior 3 months

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
NCT01558271A1DULA_SC_0p75MG_QW52arm, responders190 / 280R0011754:Results
NCT01558271A2LIRA_SC_0p9MG_QD52arm, responders82 / 136R0011754:Results
NCT01733758A2ALBI_SC_30MG_QW52arm, responders82 / 148registry:outcomes
NCT01733758A3ALBI_SC_50MG_QW52arm, responders85 / 135registry:outcomes
NCT01733758A4LIRA_SC_0p9MG_QD52arm, responders57 / 95registry:outcomes
PIONEER 9A1SEMA_PO_3MG_QD52arm, responders19 / 49registry:outcomes
PIONEER 9A2SEMA_PO_7MG_QD52arm, responders29 / 49registry:outcomes
PIONEER 9A3SEMA_PO_14MG_QD52arm, responders33 / 48registry:outcomes
PIONEER 9A4LIRA_SC_0p9MG_QD52arm, responders20 / 48registry:outcomes
PIONEER 9A5PLACEBO52arm, responders4 / 49registry:outcomes
AMPLITUDE-MA1EFPE_SC_2MG_QW56arm, responders54 / 100count_from_percentR0007136:Figure 2
AMPLITUDE-MA2EFPE_SC_4MG_QW56arm, responders58 / 101count_from_percentR0007136:Figure 2
AMPLITUDE-MA3EFPE_SC_6MG_QW56arm, responders59 / 103count_from_percentR0007136:Figure 2
AMPLITUDE-MA4PLACEBO56arm, responders24 / 102count_from_percentR0007136:Figure 2

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