LivingGLP1
Network meta-analysis

HbA1c below 7 percent

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

weeks 20 to 36 (target week 26)Hypothetical (as if everyone stayed on treatment)Doses of a drug pooledOdds ratio
10
Randomized trials
10
Treatments
5,345
Participants
2,874
Events

In plain language

Across 10 trials with 5,345 participants, 7 of 9 treatments had a clearly better result than placebo on HbA1c below 7 percent, and for 2 the evidence could not tell them apart from placebo. The most favorable estimate was for Tirzepatide injection: odds ratio 18.80 (95% credible interval 5.15 to 47.94).

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.
DULA_SCIGLARLIXI_SCINS_GLARGINELIRA_SCLIXI_SCPLACEBOSEMA_POSEMA_SCSITAGLIPTINTIRZ_SC
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.
0.51245102050← favors referencefavors treatment →Tirzepatide injectionSemaglutide injectionDulaglutide injectionSemaglutide tabletInsulin glargine with lixisenati…Liraglutide injectionInsulin glargineSitagliptinLixisenatide injection
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
Tirzepatide injection
TIRZ_SC
18.80 (5.15 to 47.94)3.75 to 63.7324.85 (11.79 to 52.39)Better
Semaglutide injection
SEMA_SC
14.58 (4.66 to 37.39)3.61 to 51.8115.64 (8.09 to 30.25)Better
Dulaglutide injection
DULA_SC
11.88 (3.89 to 24.98)2.79 to 33.0516.19 (8.88 to 29.53)Better
Semaglutide tablet
SEMA_PO
10.57 (3.78 to 21.20)2.48 to 29.0613.42 (7.63 to 23.60)Better
Insulin glargine with lixisenatide injection
IGLARLIXI_SC
10.55 (2.71 to 24.87)1.91 to 32.3813.51 (7.11 to 25.66)Better
Liraglutide injection
LIRA_SC
8.20 (2.71 to 18.56)1.94 to 25.529.74 (5.27 to 18.00)Better
Insulin glargine
INS_GLARGINE
5.08 (1.50 to 11.62)1.01 to 15.106.96 (3.68 to 13.14)Better
Sitagliptin
SITAGLIPTIN
3.70 (0.86 to 9.76)0.63 to 12.794.76 (2.34 to 9.68)Unclear
Lixisenatide injection
LIXI_SC
1.91 (0.67 to 3.92)0.47 to 5.282.16 (1.32 to 3.53)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 columnPLACEBOTIRZ_SCSEMA_SCDULA_SCSEMA_POIGLARLIXI_SCLIRA_SCINS_GLARGINESITAGLIPTINLIXI_SC
PLACEBOPLACEBO0.05
0.02 to 0.19		0.07
0.03 to 0.21		0.08
0.04 to 0.26		0.09
0.05 to 0.26		0.09
0.04 to 0.37		0.12
0.05 to 0.37		0.20
0.09 to 0.67		0.27
0.10 to 1.17		0.52
0.25 to 1.48
TIRZ_SC18.80
5.15 to 47.94		TIRZ_SC1.30
0.26 to 5.04		1.58
0.59 to 4.23		1.79
0.53 to 5.38		1.81
0.51 to 6.53		2.30
0.58 to 7.72		3.73
1.26 to 11.66		5.24
1.19 to 20.69		10.06
2.60 to 32.67
SEMA_SC14.58
4.66 to 37.39		0.77
0.20 to 3.86		SEMA_SC1.21
0.37 to 5.48		1.37
0.41 to 5.46		1.38
0.38 to 7.12		1.79
0.47 to 7.11		2.84
0.82 to 13.54		4.01
0.96 to 21.01		7.69
2.24 to 30.88
DULA_SC11.88
3.89 to 24.98		0.63
0.24 to 1.70		0.82
0.18 to 2.71		DULA_SC1.13
0.46 to 2.44		1.13
0.43 to 3.16		1.48
0.45 to 4.08		2.34
1.25 to 4.53		3.28
1.03 to 10.33		6.35
2.10 to 16.39
SEMA_PO10.57
3.78 to 21.20		0.56
0.19 to 1.87		0.73
0.18 to 2.45		0.88
0.41 to 2.16		SEMA_PO1.00
0.34 to 3.40		1.30
0.51 to 3.01		2.08
0.82 to 6.02		2.91
1.24 to 7.36		5.60
1.80 to 16.29
IGLARLIXI_SC10.55
2.71 to 24.87		0.55
0.15 to 1.98		0.73
0.14 to 2.64		0.88
0.32 to 2.32		1.00
0.29 to 2.92		IGLARLIXI_SC1.28
0.30 to 4.23		2.06
0.83 to 5.15		2.89
0.67 to 11.49		5.59
2.07 to 12.45
LIRA_SC8.20
2.71 to 18.56		0.44
0.13 to 1.72		0.56
0.14 to 2.13		0.68
0.25 to 2.25		0.77
0.33 to 1.98		0.78
0.24 to 3.31		LIRA_SC1.59
0.53 to 5.93		2.24
0.70 to 8.51		4.34
1.29 to 14.69
INS_GLARGINE5.08
1.50 to 11.62		0.27
0.09 to 0.80		0.35
0.07 to 1.22		0.43
0.22 to 0.80		0.48
0.17 to 1.21		0.48
0.19 to 1.21		0.63
0.17 to 1.87		INS_GLARGINE1.41
0.37 to 4.96		2.71
0.87 to 6.94
SITAGLIPTIN3.70
0.86 to 9.76		0.19
0.05 to 0.84		0.25
0.05 to 1.05		0.30
0.10 to 0.97		0.34
0.14 to 0.81		0.35
0.09 to 1.49		0.45
0.12 to 1.44		0.71
0.20 to 2.72		SITAGLIPTIN1.93
0.44 to 7.08
LIXI_SC1.91
0.67 to 3.92		0.10
0.03 to 0.38		0.13
0.03 to 0.45		0.16
0.06 to 0.48		0.18
0.06 to 0.56		0.18
0.08 to 0.48		0.23
0.07 to 0.77		0.37
0.14 to 1.15		0.52
0.14 to 2.25		LIXI_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.318 (95% CrI 0.081 to 0.949), log scale
Residual deviance
22.1 for 22 data points
DIC
42.9 (pD 20.8)
Largest R-hat
1.003
Smallest ESS
bulk 1,566, tail 1,778
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
0.176
I squared
41%
Q (total)
5.11 on 3 df, P = 0.164
Q (between designs)
4.12, P = 0.128

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; 10 of 10
Background glucose lowering therapy (stratum S0 to S4)
effect modifier, prognostic factor; 10 of 10
Diabetes duration (years)
effect modifier, prognostic factor; 10 of 10
NCT03131687
S000010
8.13S18.51
PIONEER 4
S000133
7.98S17.6
NCT01476475
S000191
8.05S16.7
PIONEER 10
S000234
8.31S19.36
NCT01584232
S000246
8.05S18.85
SUSTAIN 9
S000483
8.05S19.7
PIONEER 12
S000522
8.12S15.63
AWARD-2
S001130
8.14S19.1
LIXILAN JP-O1
S002018
8.39S18.67
GETGOAL-M
S002188
8.05S16.2

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, Diabetes duration: design means range from 5.6 (SEMA_PO vs SITAGLIPTIN) to 9.7 (PLACEBO vs SEMA_SC) years; threshold 3
  • NoteOutcome assessment, time point: selected time points span 24 to 30 weeks
  • NoteOutcome assessment, analysis set: mixed: full_analysis 5, modified_itt 5
  • NoteOutcome assessment, definition: mixed: HbA1c below 7.0 percent 1, HbA1c below 7.0 percent, LOCF, mITT on treatment dataset 1, HbA1c below 7%; missing week 26 counted as nonresponder 1, not stated 7
  • NoteOutcome assessment, proportion method: mixed: imputed 1, not stated 5, not_stated 3, observed 1
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 7, not stated 3
  • NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 9, not stated 1
  • NoteRisk of bias, blinding: mixed: double_blind 5, open_label 4, single_blind 1
  • NoteData handling, input conversions: arms_combined 5, count_from_percent 9
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
NCT0313168726modified_ittHbA1c below 7.0 percent, LOCF, mITT on treatment datasetnot statednot statedimputedhypotheticalhypotheticaldouble_blindindustry2017age 18 to 75; T2D at least 6 months; HbA1c 7.0 to 10.5%; BMI 23 to 50; diet and exercise or metformin
PIONEER 426full_analysisnot statednot statednot statedobservedhypotheticalhypotheticaldouble_blindindustry2016Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more
NCT0147647524modified_ittnot statednot statednot statednot_statedhypotheticalhypotheticalopen_labelindustry2011Adults with T2D; HbA1c 7 to 10 percent on metformin at least 1.5 g/day; insulin naive
PIONEER 1026full_analysisHbA1c below 7.0 percentnot statednot statednot statedhypotheticalhypotheticalsingle_blindindustry2017Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
NCT0158423226full_analysisnot statednot statednot statednot statednot statedhypotheticalopen_labelindustry2012Japanese adults 20 years or older; BMI 18.5 to less than 35 kg/m2; HbA1c 7.0 to 10.0 percent; on sulfonylurea and/or biguanide
SUSTAIN 930full_analysisnot statednot statednot statednot_statednot statednot stateddouble_blindindustry2017adults 18 or older (20 in Japan); HbA1c 7.0 to 10.5 percent; stable SGLT2i with or without metformin or SU
PIONEER 1226full_analysisnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2019adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent
AWARD-226modified_ittnot statednot statednot statednot statednot statedhypotheticalopen_labelindustry2010type 2 diabetes on metformin and glimepiride
LIXILAN JP-O126modified_ittHbA1c below 7%; missing week 26 counted as nonrespondernot statednot statednot statedhypotheticalhypotheticalopen_labelindustry2016insulin naive Japanese adults; HbA1c 7.5 to 10%; FPG 13.8 mmol/L or less; one or two OADs
GETGOAL-M24modified_ittnot statednot statednot statednot_statedhypotheticalhypotheticaldouble_blindindustry2008type 2 diabetes on metformin 1.5 g/day or more for 3 months; HbA1c 7 to 10 percent; FPG 13.9 mmol/L or less

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
NCT03131687A1PLACEBO26arm, responders6 / 51R0016215:Supplement Table 4
NCT03131687A2+A3+A4+A5TIRZ_SC26arm, responders141 / 210arms_combinedR0016215:Supplement Table 4
NCT03131687A6DULA_SC26arm, responders28 / 54R0016215:Supplement Table 4
PIONEER 4A1SEMA_PO26arm, responders172 / 238count_from_percentR0015836:Figure 2C
PIONEER 4A2LIRA_SC26arm, responders160 / 245count_from_percentR0015836:Figure 2C
PIONEER 4A3PLACEBO26arm, responders18 / 112count_from_percentR0015836:Figure 2C
NCT01476475A1IGLARLIXI_SC24arm, responders135 / 160count_from_percentregistry:outcomes
NCT01476475A2INS_GLARGINE24arm, responders126 / 161count_from_percentregistry:outcomes
PIONEER 10A1+A2+A3SEMA_PO26arm, responders253 / 370arms_combinedR0018421:Table 4
PIONEER 10A4DULA_SC26arm, responders45 / 62R0018421:Table 4
NCT01584232A1DULA_SC26arm, responders127 / 178R0016159:Results
NCT01584232A2INS_GLARGINE26arm, responders82 / 179R0016159:Results
SUSTAIN 9A1SEMA_SC30arm, responders119 / 151count_from_percentR0021710:Figure 2
SUSTAIN 9A2PLACEBO30arm, responders29 / 151count_from_percentR0021710:Figure 2
PIONEER 12A1+A2+A3SEMA_PO26arm, responders578 / 934arms_combinedR0019776:Table 2
PIONEER 12A4SITAGLIPTIN26arm, responders122 / 334R0019776:Table 2
AWARD-2A1+A2DULA_SC26arm, responders275 / 529arms_combinedregistry:outcomes
AWARD-2A3INS_GLARGINE26arm, responders84 / 258registry:outcomes
LIXILAN JP-O1A1IGLARLIXI_SC26arm, responders105 / 161R0015751:Table 2
LIXILAN JP-O1A2LIXI_SC26arm, responders31 / 160R0015751:Table 2
GETGOAL-MA1+A2LIXI_SC24arm, responders202 / 483count_from_percent;arms_combinedR0025872:Results
GETGOAL-MA3PLACEBO24arm, responders36 / 164count_from_percentR0025872:Results

Rerun this analysis yourself

Remove treatments or trials and refit the frequentist and Bayesian models in your browser, with the same methods as the published analysis.

Open in the NMA lab