LivingGLP1
Network meta-analysis

HbA1c change

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

weeks 20 to 36 (target week 26)Not stated by the trialsEach dose separatelyMean difference
14
Randomized trials
26
Treatments
4,530
Participants
43
Trial arms

In plain language

Across 14 trials with 4,530 participants, 11 of 25 treatments had a clearly better result than placebo on HbA1c change, and for 14 the evidence could not tell them apart from placebo. The most favorable estimate was for Ecnoglutide 1.2 mg injection once weekly: mean difference -1.79 percentage points (95% credible interval -2.52 to -0.94).

Lower 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_QWDULA_SC_1p5MG_QWECNO_SC_0p4MG_QWECNO_SC_0p8MG_QWECNO_SC_1p2MG_QWEFPE_SC_2MG_QWEFPE_SC_4MG_QWEFPE_SC_6MG_QWEXENER_SC_2MG_QWEXEN_SC_10UG_BIDGLIBENCLAMIDEGLICLAZIDEGLIMEPIRIDEINS_NPHLIRAMETF_SC_1p2-1500MG_QDLIRA_SC_0p9MG_QDLIRA_SC_1p8MG_QDLIRA_SC_FLEX_0p6-1p2-1p8_QDMETFORMINPIOGLITAZONEPLACEBOSEMA_SC_0p5MG_QWSEMA_SC_1p0MG_QWSITAGLIPTIN
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

Mean difference in percentage points. Lower values favor the treatment.
-3-2-1012← favors treatmentfavors reference →Ecnoglutide 1.2 mg injection onc…Dulaglutide 1.5 mg subcutaneous …Semaglutide 1.0 mg subcutaneous …Liraglutide 1.8 mg subcutaneous …Dulaglutide 0.75 mg subcutaneous…Albiglutide 50 mg subcutaneous o…Semaglutide 0.5 mg subcutaneous …Liraglutide and metformin 1.2 to…Liraglutide flexible dose inject…Liraglutide 0.9 mg injection onc…Ecnoglutide 0.8 mg injection onc…PioglitazoneAlbiglutide 30 mg subcutaneous o…Ecnoglutide 0.4 mg injection onc…Exenatide extended release 2 mg …MetforminGlimepirideNPH insulinExenatide 10 ug subcutaneous twi…GliclazideGlibenclamideSitagliptinEfpeglenatide 6 mg subcutaneous …Efpeglenatide 4 mg subcutaneous …Efpeglenatide 2 mg subcutaneous …
Versus Placebo. 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 MD (95% CrI)95% prediction intervalFrequentist MD (95% CI)Verdict
Ecnoglutide 1.2 mg injection once weekly
ECNO_SC_1p2MG_QW
-1.79 (-2.52 to -0.94)-2.75 to -0.67-1.84 (-2.29 to -1.39)Better
Dulaglutide 1.5 mg subcutaneous once weekly
DULA_SC_1p5MG_QW
-1.73 (-2.33 to -0.52)-2.55 to -0.23-1.89 (-2.23 to -1.56)Better
Semaglutide 1.0 mg subcutaneous once weekly
SEMA_SC_1p0MG_QW
-1.54 (-2.21 to -0.74)-2.52 to -0.44-1.56 (-1.87 to -1.25)Better
Liraglutide 1.8 mg subcutaneous once daily
LIRA_SC_1p8MG_QD
-1.51 (-1.98 to -0.27)-2.18 to -0.02-1.78 (-2.06 to -1.49)Better
Dulaglutide 0.75 mg subcutaneous once weekly
DULA_SC_0p75MG_QW
-1.48 (-1.91 to -0.58)-2.20 to -0.30-1.60 (-1.83 to -1.36)Better
Albiglutide 50 mg subcutaneous once weekly
ALBI_SC_50MG_QW
-1.47 (-2.00 to -0.63)-2.31 to -0.38-1.55 (-1.77 to -1.33)Better
Semaglutide 0.5 mg subcutaneous once weekly
SEMA_SC_0p5MG_QW
-1.44 (-2.09 to -0.66)-2.41 to -0.35-1.47 (-1.76 to -1.18)Better
Liraglutide and metformin 1.2 to 1500 mg injection once daily
LIRAMETF_SC_1p2-1500MG_QD
-1.43 (-2.12 to 0.05)-2.27 to 0.29-1.77 (-2.23 to -1.31)Unclear
Liraglutide flexible dose injection once daily
LIRA_SC_FLEX_0p6-1p2-1p8_QD
-1.34 (-2.04 to 0.12)-2.19 to 0.36-1.67 (-2.15 to -1.19)Unclear
Liraglutide 0.9 mg injection once daily
LIRA_SC_0p9MG_QD
-1.31 (-1.63 to -0.54)-1.95 to -0.22-1.44 (-1.62 to -1.25)Better
Ecnoglutide 0.8 mg injection once weekly
ECNO_SC_0p8MG_QW
-1.31 (-2.03 to -0.45)-2.28 to -0.20-1.35 (-1.80 to -0.90)Better
Pioglitazone
PIOGLITAZONE
-1.28 (-1.95 to 0.18)-2.11 to 0.46-1.62 (-2.03 to -1.21)Unclear
Albiglutide 30 mg subcutaneous once weekly
ALBI_SC_30MG_QW
-1.28 (-1.76 to -0.47)-2.07 to -0.19-1.35 (-1.56 to -1.13)Better
Ecnoglutide 0.4 mg injection once weekly
ECNO_SC_0p4MG_QW
-1.22 (-1.95 to -0.38)-2.21 to -0.11-1.26 (-1.71 to -0.81)Better
Exenatide extended release 2 mg subcutaneous once weekly
EXENER_SC_2MG_QW
-1.19 (-1.82 to 0.27)-2.01 to 0.49-1.52 (-1.92 to -1.11)Unclear
Metformin
METFORMIN
-1.17 (-1.71 to 0.13)-1.86 to 0.39-1.50 (-1.84 to -1.16)Unclear
Glimepiride
GLIMEPIRIDE
-1.16 (-1.68 to 0.01)-1.95 to 0.28-1.35 (-1.67 to -1.03)Unclear
NPH insulin
INS_NPH
-1.10 (-2.13 to 0.60)-2.25 to 0.75-1.51 (-2.27 to -0.75)Unclear
Exenatide 10 ug subcutaneous twice daily
EXEN_SC_10UG_BID
-0.90 (-1.58 to 0.57)-1.74 to 0.79-1.23 (-1.68 to -0.78)Unclear
Gliclazide
GLICLAZIDE
-0.81 (-1.53 to 0.66)-1.69 to 0.91-1.12 (-1.61 to -0.64)Unclear
Glibenclamide
GLIBENCLAMIDE
-0.79 (-1.40 to 0.39)-1.65 to 0.59-0.93 (-1.26 to -0.59)Unclear
Sitagliptin
SITAGLIPTIN
-0.76 (-1.36 to 0.55)-1.50 to 0.79-1.09 (-1.47 to -0.72)Unclear
Efpeglenatide 6 mg subcutaneous once weekly
EFPE_SC_6MG_QW
-0.72 (-2.55 to 1.12)-2.63 to 1.22-1.00 (-3.37 to 1.37)Unclear
Efpeglenatide 4 mg subcutaneous once weekly
EFPE_SC_4MG_QW
-0.52 (-2.33 to 1.31)-2.42 to 1.41-0.80 (-3.17 to 1.57)Unclear
Efpeglenatide 2 mg subcutaneous once weekly
EFPE_SC_2MG_QW
-0.21 (-2.07 to 1.60)-2.15 to 1.71-0.50 (-2.87 to 1.87)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: mean difference 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 columnPLACEBOECNO_SC_1p2MG_QWDULA_SC_1p5MG_QWSEMA_SC_1p0MG_QWLIRA_SC_1p8MG_QDDULA_SC_0p75MG_QWALBI_SC_50MG_QWSEMA_SC_0p5MG_QWLIRAMETF_SC_1p2-1500MG_QDLIRA_SC_FLEX_0p6-1p2-1p8_QDLIRA_SC_0p9MG_QDECNO_SC_0p8MG_QWPIOGLITAZONEALBI_SC_30MG_QWECNO_SC_0p4MG_QWEXENER_SC_2MG_QWMETFORMINGLIMEPIRIDEINS_NPHEXEN_SC_10UG_BIDGLICLAZIDEGLIBENCLAMIDESITAGLIPTINEFPE_SC_6MG_QWEFPE_SC_4MG_QWEFPE_SC_2MG_QW
PLACEBOPLACEBO1.79
0.94 to 2.52
1.73
0.52 to 2.33
1.54
0.74 to 2.21
1.51
0.27 to 1.98
1.48
0.58 to 1.91
1.47
0.63 to 2.00
1.44
0.66 to 2.09
1.43
-0.05 to 2.12
1.34
-0.12 to 2.04
1.31
0.54 to 1.63
1.31
0.45 to 2.03
1.28
-0.18 to 1.95
1.28
0.47 to 1.76
1.22
0.38 to 1.95
1.19
-0.27 to 1.82
1.17
-0.13 to 1.71
1.16
-0.01 to 1.68
1.10
-0.60 to 2.13
0.90
-0.57 to 1.58
0.81
-0.66 to 1.53
0.79
-0.39 to 1.40
0.76
-0.55 to 1.36
0.72
-1.12 to 2.55
0.52
-1.31 to 2.33
0.21
-1.60 to 2.07
ECNO_SC_1p2MG_QW-1.79
-2.52 to -0.94
ECNO_SC_1p2MG_QW-0.07
-1.44 to 0.89
-0.26
-1.29 to 0.83
-0.29
-1.75 to 0.50
-0.33
-1.46 to 0.53
-0.33
-1.39 to 0.64
-0.36
-1.37 to 0.71
-0.36
-1.97 to 0.58
-0.45
-2.06 to 0.51
-0.49
-1.55 to 0.31
-0.48
-1.27 to 0.30
-0.53
-2.14 to 0.42
-0.53
-1.60 to 0.41
-0.57
-1.37 to 0.19
-0.62
-2.21 to 0.28
-0.62
-2.13 to 0.18
-0.65
-1.97 to 0.21
-0.68
-2.49 to 0.52
-0.91
-2.49 to 0.04
-0.98
-2.60 to -0.03
-1.02
-2.36 to -0.02
-1.04
-2.51 to -0.17
-1.06
-3.05 to 0.93
-1.26
-3.20 to 0.72
-1.56
-3.54 to 0.43
DULA_SC_1p5MG_QW-1.73
-2.33 to -0.52
0.07
-0.89 to 1.44
DULA_SC_1p5MG_QW-0.19
-1.08 to 1.19
-0.20
-1.27 to 0.61
-0.25
-0.86 to 0.53
-0.26
-1.13 to 0.99
-0.28
-1.14 to 1.11
-0.27
-1.56 to 0.68
-0.37
-1.62 to 0.60
-0.41
-1.17 to 0.54
-0.40
-1.36 to 0.98
-0.42
-1.63 to 0.47
-0.45
-1.29 to 0.70
-0.49
-1.46 to 0.90
-0.52
-1.74 to 0.34
-0.53
-1.63 to 0.23
-0.56
-1.30 to 0.10
-0.59
-2.04 to 0.54
-0.81
-1.98 to 0.04
-0.89
-2.15 to 0.10
-0.94
-2.02 to 0.20
-0.94
-2.00 to -0.18
-0.95
-2.91 to 1.15
-1.15
-3.10 to 0.92
-1.45
-3.40 to 0.66
SEMA_SC_1p0MG_QW-1.54
-2.21 to -0.74
0.26
-0.83 to 1.29
0.19
-1.19 to 1.08
SEMA_SC_1p0MG_QW-0.02
-1.47 to 0.71
-0.06
-1.19 to 0.72
-0.06
-1.13 to 0.81
-0.09
-0.81 to 0.63
-0.09
-1.72 to 0.77
-0.18
-1.80 to 0.72
-0.22
-1.29 to 0.50
-0.21
-1.28 to 0.83
-0.24
-1.85 to 0.61
-0.26
-1.30 to 0.61
-0.31
-1.40 to 0.77
-0.34
-1.99 to 0.51
-0.35
-1.88 to 0.41
-0.38
-1.75 to 0.43
-0.41
-2.28 to 0.77
-0.63
-2.28 to 0.26
-0.72
-2.38 to 0.20
-0.75
-2.07 to 0.15
-0.76
-2.30 to 0.04
-0.80
-2.77 to 1.18
-1.00
-2.95 to 0.94
-1.29
-3.27 to 0.69
LIRA_SC_1p8MG_QD-1.51
-1.98 to -0.27
0.29
-0.50 to 1.75
0.20
-0.61 to 1.27
0.02
-0.71 to 1.47
LIRA_SC_1p8MG_QD-0.05
-0.61 to 0.97
-0.06
-0.65 to 1.17
-0.07
-0.77 to 1.36
-0.06
-0.80 to 0.58
-0.16
-0.90 to 0.51
-0.21
-0.64 to 0.66
-0.19
-0.98 to 1.21
-0.22
-1.07 to 0.54
-0.26
-0.87 to 0.94
-0.28
-1.07 to 1.15
-0.32
-1.13 to 0.41
-0.33
-0.81 to 0.09
-0.36
-1.08 to 0.55
-0.37
-1.64 to 0.79
-0.60
-1.54 to 0.28
-0.69
-1.37 to -0.00
-0.74
-1.49 to 0.39
-0.73
-1.48 to -0.02
-0.70
-2.61 to 1.39
-0.90
-2.82 to 1.20
-1.20
-3.11 to 0.91
DULA_SC_0p75MG_QW-1.48
-1.91 to -0.58
0.33
-0.53 to 1.46
0.25
-0.53 to 0.86
0.06
-0.72 to 1.19
0.05
-0.97 to 0.61
DULA_SC_0p75MG_QW-0.00
-0.77 to 0.93
-0.02
-0.79 to 1.09
-0.02
-1.29 to 0.73
-0.11
-1.36 to 0.66
-0.16
-0.76 to 0.44
-0.15
-1.01 to 0.96
-0.17
-1.39 to 0.53
-0.20
-0.93 to 0.68
-0.24
-1.10 to 0.91
-0.27
-1.47 to 0.41
-0.28
-1.36 to 0.30
-0.31
-1.06 to 0.20
-0.35
-1.78 to 0.71
-0.56
-1.72 to 0.15
-0.65
-1.89 to 0.17
-0.69
-1.65 to 0.20
-0.69
-1.74 to -0.09
-0.71
-2.63 to 1.27
-0.90
-2.80 to 1.06
-1.20
-3.09 to 0.79
ALBI_SC_50MG_QW-1.47
-2.00 to -0.63
0.33
-0.64 to 1.39
0.26
-0.99 to 1.13
0.06
-0.81 to 1.13
0.06
-1.17 to 0.65
0.00
-0.93 to 0.77
ALBI_SC_50MG_QW-0.03
-0.90 to 1.04
-0.02
-1.46 to 0.78
-0.12
-1.55 to 0.69
-0.15
-0.94 to 0.44
-0.15
-1.10 to 0.94
-0.17
-1.66 to 0.60
-0.20
-0.92 to 0.52
-0.24
-1.21 to 0.86
-0.26
-1.71 to 0.49
-0.27
-1.59 to 0.36
-0.30
-1.54 to 0.46
-0.35
-2.02 to 0.77
-0.55
-2.03 to 0.27
-0.65
-2.06 to 0.17
-0.68
-1.82 to 0.15
-0.68
-2.03 to 0.04
-0.73
-2.62 to 1.26
-0.91
-2.81 to 1.04
-1.22
-3.11 to 0.76
SEMA_SC_0p5MG_QW-1.44
-2.09 to -0.66
0.36
-0.71 to 1.37
0.28
-1.11 to 1.14
0.09
-0.63 to 0.81
0.07
-1.36 to 0.77
0.02
-1.09 to 0.79
0.03
-1.04 to 0.90
SEMA_SC_0p5MG_QW-0.00
-1.66 to 0.85
-0.09
-1.72 to 0.79
-0.13
-1.17 to 0.57
-0.13
-1.19 to 0.91
-0.16
-1.80 to 0.70
-0.17
-1.18 to 0.66
-0.22
-1.29 to 0.80
-0.25
-1.88 to 0.59
-0.26
-1.78 to 0.48
-0.28
-1.63 to 0.49
-0.32
-2.20 to 0.85
-0.54
-2.13 to 0.32
-0.62
-2.24 to 0.27
-0.66
-2.02 to 0.27
-0.67
-2.19 to 0.13
-0.71
-2.68 to 1.22
-0.90
-2.87 to 1.01
-1.22
-3.16 to 0.73
LIRAMETF_SC_1p2-1500MG_QD-1.43
-2.12 to 0.05
0.36
-0.58 to 1.97
0.27
-0.68 to 1.56
0.09
-0.77 to 1.72
0.06
-0.58 to 0.80
0.02
-0.73 to 1.29
0.02
-0.78 to 1.46
0.00
-0.85 to 1.66
LIRAMETF_SC_1p2-1500MG_QD-0.10
-0.86 to 0.70
-0.14
-0.80 to 1.04
-0.13
-1.05 to 1.49
-0.16
-1.11 to 0.82
-0.18
-0.96 to 1.25
-0.21
-1.14 to 1.41
-0.26
-1.15 to 0.67
-0.27
-0.94 to 0.45
-0.29
-1.13 to 0.88
-0.31
-1.64 to 1.05
-0.55
-1.60 to 0.58
-0.63
-1.52 to 0.34
-0.68
-1.60 to 0.71
-0.67
-1.53 to 0.30
-0.64
-2.66 to 1.61
-0.84
-2.83 to 1.40
-1.14
-3.14 to 1.13
LIRA_SC_FLEX_0p6-1p2-1p8_QD-1.34
-2.04 to 0.12
0.45
-0.51 to 2.06
0.37
-0.60 to 1.62
0.18
-0.72 to 1.80
0.16
-0.51 to 0.90
0.11
-0.66 to 1.36
0.12
-0.69 to 1.55
0.09
-0.79 to 1.72
0.10
-0.70 to 0.86
LIRA_SC_FLEX_0p6-1p2-1p8_QD-0.04
-0.72 to 1.08
-0.03
-0.96 to 1.58
-0.06
-1.05 to 0.88
-0.09
-0.89 to 1.33
-0.11
-1.07 to 1.43
-0.16
-1.08 to 0.75
-0.17
-0.88 to 0.54
-0.20
-1.07 to 0.94
-0.22
-1.52 to 1.10
-0.45
-1.51 to 0.66
-0.53
-1.43 to 0.44
-0.58
-1.52 to 0.78
-0.58
-1.48 to 0.38
-0.55
-2.54 to 1.75
-0.74
-2.70 to 1.51
-1.05
-3.04 to 1.21
LIRA_SC_0p9MG_QD-1.31
-1.63 to -0.54
0.49
-0.31 to 1.55
0.41
-0.54 to 1.17
0.22
-0.50 to 1.29
0.21
-0.66 to 0.64
0.16
-0.44 to 0.76
0.15
-0.44 to 0.94
0.13
-0.57 to 1.17
0.14
-1.04 to 0.80
0.04
-1.08 to 0.72
LIRA_SC_0p9MG_QD0.01
-0.77 to 1.05
-0.01
-1.22 to 0.66
-0.05
-0.60 to 0.72
-0.08
-0.85 to 1.00
-0.11
-1.25 to 0.53
-0.12
-1.10 to 0.36
-0.15
-1.04 to 0.48
-0.19
-1.69 to 0.87
-0.40
-1.60 to 0.32
-0.49
-1.63 to 0.22
-0.53
-1.28 to 0.12
-0.53
-1.59 to 0.06
-0.55
-2.43 to 1.36
-0.74
-2.61 to 1.15
-1.04
-2.90 to 0.88
ECNO_SC_0p8MG_QW-1.31
-2.03 to -0.45
0.48
-0.30 to 1.27
0.40
-0.98 to 1.36
0.21
-0.83 to 1.28
0.19
-1.21 to 0.98
0.15
-0.96 to 1.01
0.15
-0.94 to 1.10
0.13
-0.91 to 1.19
0.13
-1.49 to 1.05
0.03
-1.58 to 0.96
-0.01
-1.05 to 0.77
ECNO_SC_0p8MG_QW-0.03
-1.68 to 0.91
-0.05
-1.13 to 0.88
-0.08
-0.89 to 0.71
-0.13
-1.71 to 0.76
-0.14
-1.63 to 0.67
-0.16
-1.52 to 0.72
-0.19
-2.03 to 0.99
-0.42
-2.02 to 0.53
-0.51
-2.08 to 0.45
-0.54
-1.88 to 0.44
-0.55
-2.06 to 0.31
-0.58
-2.58 to 1.34
-0.79
-2.75 to 1.20
-1.10
-3.04 to 0.87
PIOGLITAZONE-1.28
-1.95 to 0.18
0.53
-0.42 to 2.14
0.42
-0.47 to 1.63
0.24
-0.61 to 1.85
0.22
-0.54 to 1.07
0.17
-0.53 to 1.39
0.17
-0.60 to 1.66
0.16
-0.70 to 1.80
0.16
-0.82 to 1.11
0.06
-0.88 to 1.05
0.01
-0.66 to 1.22
0.03
-0.91 to 1.68
PIOGLITAZONE-0.03
-0.79 to 1.38
-0.05
-1.00 to 1.57
-0.10
-0.82 to 0.63
-0.11
-0.81 to 0.59
-0.14
-0.91 to 0.91
-0.15
-1.38 to 1.06
-0.38
-1.30 to 0.58
-0.47
-1.40 to 0.54
-0.53
-1.43 to 0.85
-0.51
-1.18 to 0.21
-0.48
-2.50 to 1.79
-0.67
-2.69 to 1.55
-0.98
-2.96 to 1.26
ALBI_SC_30MG_QW-1.28
-1.76 to -0.47
0.53
-0.41 to 1.60
0.45
-0.70 to 1.29
0.26
-0.61 to 1.30
0.26
-0.94 to 0.87
0.20
-0.68 to 0.93
0.20
-0.52 to 0.92
0.17
-0.66 to 1.18
0.18
-1.25 to 0.96
0.09
-1.33 to 0.89
0.05
-0.72 to 0.60
0.05
-0.88 to 1.13
0.03
-1.38 to 0.79
ALBI_SC_30MG_QW-0.04
-0.96 to 1.03
-0.06
-1.48 to 0.69
-0.08
-1.36 to 0.56
-0.11
-1.25 to 0.65
-0.15
-1.84 to 0.97
-0.35
-1.79 to 0.45
-0.44
-1.84 to 0.36
-0.49
-1.59 to 0.34
-0.48
-1.83 to 0.20
-0.53
-2.42 to 1.45
-0.72
-2.59 to 1.23
-1.03
-2.90 to 0.93
ECNO_SC_0p4MG_QW-1.22
-1.95 to -0.38
0.57
-0.19 to 1.37
0.49
-0.90 to 1.46
0.31
-0.77 to 1.40
0.28
-1.15 to 1.07
0.24
-0.91 to 1.10
0.24
-0.86 to 1.21
0.22
-0.80 to 1.29
0.21
-1.41 to 1.14
0.11
-1.43 to 1.07
0.08
-1.00 to 0.85
0.08
-0.71 to 0.89
0.05
-1.57 to 1.00
0.04
-1.03 to 0.96
ECNO_SC_0p4MG_QW-0.04
-1.65 to 0.87
-0.05
-1.54 to 0.77
-0.08
-1.40 to 0.81
-0.10
-1.92 to 1.11
-0.32
-1.93 to 0.62
-0.42
-2.04 to 0.56
-0.45
-1.78 to 0.54
-0.46
-2.00 to 0.42
-0.50
-2.47 to 1.46
-0.71
-2.64 to 1.24
-1.01
-2.96 to 1.01
EXENER_SC_2MG_QW-1.19
-1.82 to 0.27
0.62
-0.28 to 2.21
0.52
-0.34 to 1.74
0.34
-0.51 to 1.99
0.32
-0.41 to 1.13
0.27
-0.41 to 1.47
0.26
-0.49 to 1.71
0.25
-0.59 to 1.88
0.26
-0.67 to 1.15
0.16
-0.75 to 1.08
0.11
-0.53 to 1.25
0.13
-0.76 to 1.71
0.10
-0.63 to 0.82
0.06
-0.69 to 1.48
0.04
-0.87 to 1.65
EXENER_SC_2MG_QW-0.01
-0.69 to 0.65
-0.03
-0.78 to 0.97
-0.05
-1.26 to 1.17
-0.28
-1.21 to 0.69
-0.37
-1.31 to 0.62
-0.42
-1.33 to 0.91
-0.41
-1.06 to 0.26
-0.39
-2.38 to 1.85
-0.58
-2.58 to 1.67
-0.88
-2.85 to 1.37
METFORMIN-1.17
-1.71 to 0.13
0.62
-0.18 to 2.13
0.53
-0.23 to 1.63
0.35
-0.41 to 1.88
0.33
-0.09 to 0.81
0.28
-0.30 to 1.36
0.27
-0.36 to 1.59
0.26
-0.48 to 1.78
0.27
-0.45 to 0.94
0.17
-0.54 to 0.88
0.12
-0.36 to 1.10
0.14
-0.67 to 1.63
0.11
-0.59 to 0.81
0.08
-0.56 to 1.36
0.05
-0.77 to 1.54
0.01
-0.65 to 0.69
METFORMIN-0.03
-0.68 to 0.91
-0.04
-1.22 to 1.14
-0.28
-1.18 to 0.63
-0.36
-1.03 to 0.35
-0.42
-1.21 to 0.80
-0.41
-1.04 to 0.27
-0.37
-2.33 to 1.78
-0.56
-2.50 to 1.55
-0.87
-2.79 to 1.26
GLIMEPIRIDE-1.16
-1.68 to 0.01
0.65
-0.21 to 1.97
0.56
-0.10 to 1.30
0.38
-0.43 to 1.75
0.36
-0.55 to 1.08
0.31
-0.20 to 1.06
0.30
-0.46 to 1.54
0.28
-0.49 to 1.63
0.29
-0.88 to 1.13
0.20
-0.94 to 1.07
0.15
-0.48 to 1.04
0.16
-0.72 to 1.52
0.14
-0.91 to 0.91
0.11
-0.65 to 1.25
0.08
-0.81 to 1.40
0.03
-0.97 to 0.78
0.03
-0.91 to 0.68
GLIMEPIRIDE-0.03
-1.26 to 0.98
-0.25
-1.13 to 0.41
-0.34
-1.46 to 0.59
-0.38
-1.33 to 0.74
-0.38
-1.20 to 0.20
-0.38
-2.29 to 1.71
-0.58
-2.49 to 1.51
-0.87
-2.82 to 1.25
INS_NPH-1.10
-2.13 to 0.60
0.68
-0.52 to 2.49
0.59
-0.54 to 2.04
0.41
-0.77 to 2.28
0.37
-0.79 to 1.64
0.35
-0.71 to 1.78
0.35
-0.77 to 2.02
0.32
-0.85 to 2.20
0.31
-1.05 to 1.64
0.22
-1.10 to 1.52
0.19
-0.87 to 1.69
0.19
-0.99 to 2.03
0.15
-1.06 to 1.38
0.15
-0.97 to 1.84
0.10
-1.11 to 1.92
0.05
-1.17 to 1.26
0.04
-1.14 to 1.22
0.03
-0.98 to 1.26
INS_NPH-0.23
-1.08 to 0.65
-0.31
-1.64 to 1.06
-0.35
-1.59 to 1.24
-0.36
-1.41 to 0.74
-0.35
-2.44 to 2.10
-0.55
-2.64 to 1.89
-0.85
-2.96 to 1.62
EXEN_SC_10UG_BID-0.90
-1.58 to 0.57
0.91
-0.04 to 2.49
0.81
-0.04 to 1.98
0.63
-0.26 to 2.28
0.60
-0.28 to 1.54
0.56
-0.15 to 1.72
0.55
-0.27 to 2.03
0.54
-0.32 to 2.13
0.55
-0.58 to 1.60
0.45
-0.66 to 1.51
0.40
-0.32 to 1.60
0.42
-0.53 to 2.02
0.38
-0.58 to 1.30
0.35
-0.45 to 1.79
0.32
-0.62 to 1.93
0.28
-0.69 to 1.21
0.28
-0.63 to 1.18
0.25
-0.41 to 1.13
0.23
-0.65 to 1.08
EXEN_SC_10UG_BID-0.08
-1.17 to 1.06
-0.13
-1.11 to 1.21
-0.13
-0.84 to 0.59
-0.10
-2.10 to 2.13
-0.30
-2.30 to 1.95
-0.61
-2.60 to 1.68
GLICLAZIDE-0.81
-1.53 to 0.66
0.98
0.03 to 2.60
0.89
-0.10 to 2.15
0.72
-0.20 to 2.38
0.69
0.00 to 1.37
0.65
-0.17 to 1.89
0.65
-0.17 to 2.06
0.62
-0.27 to 2.24
0.63
-0.34 to 1.52
0.53
-0.44 to 1.43
0.49
-0.22 to 1.63
0.51
-0.45 to 2.08
0.47
-0.54 to 1.40
0.44
-0.36 to 1.84
0.42
-0.56 to 2.04
0.37
-0.62 to 1.31
0.36
-0.35 to 1.03
0.34
-0.59 to 1.46
0.31
-1.06 to 1.64
0.08
-1.06 to 1.17
GLICLAZIDE-0.05
-1.03 to 1.28
-0.04
-0.99 to 0.88
-0.03
-2.02 to 2.21
-0.22
-2.22 to 1.96
-0.52
-2.54 to 1.70
GLIBENCLAMIDE-0.79
-1.40 to 0.39
1.02
0.02 to 2.36
0.94
-0.20 to 2.02
0.75
-0.15 to 2.07
0.74
-0.39 to 1.49
0.69
-0.20 to 1.65
0.68
-0.15 to 1.82
0.66
-0.27 to 2.02
0.68
-0.71 to 1.60
0.58
-0.78 to 1.52
0.53
-0.12 to 1.28
0.54
-0.44 to 1.88
0.53
-0.85 to 1.43
0.49
-0.34 to 1.59
0.45
-0.54 to 1.78
0.42
-0.91 to 1.33
0.42
-0.80 to 1.21
0.38
-0.74 to 1.33
0.35
-1.24 to 1.59
0.13
-1.21 to 1.11
0.05
-1.28 to 1.03
GLIBENCLAMIDE0.01
-1.24 to 0.86
-0.02
-1.97 to 2.09
-0.21
-2.18 to 1.89
-0.50
-2.47 to 1.59
SITAGLIPTIN-0.76
-1.36 to 0.55
1.04
0.17 to 2.51
0.94
0.18 to 2.00
0.76
-0.04 to 2.30
0.73
0.02 to 1.48
0.69
0.09 to 1.74
0.68
-0.04 to 2.03
0.67
-0.13 to 2.19
0.67
-0.30 to 1.53
0.58
-0.38 to 1.48
0.53
-0.06 to 1.59
0.55
-0.31 to 2.06
0.51
-0.21 to 1.18
0.48
-0.20 to 1.83
0.46
-0.42 to 2.00
0.41
-0.26 to 1.06
0.41
-0.27 to 1.04
0.38
-0.20 to 1.20
0.36
-0.74 to 1.41
0.13
-0.59 to 0.84
0.04
-0.88 to 0.99
-0.01
-0.86 to 1.24
SITAGLIPTIN0.03
-1.96 to 2.23
-0.17
-2.12 to 1.96
-0.48
-2.42 to 1.71
EFPE_SC_6MG_QW-0.72
-2.55 to 1.12
1.06
-0.93 to 3.05
0.95
-1.15 to 2.91
0.80
-1.18 to 2.77
0.70
-1.39 to 2.61
0.71
-1.27 to 2.63
0.73
-1.26 to 2.62
0.71
-1.22 to 2.68
0.64
-1.61 to 2.66
0.55
-1.75 to 2.54
0.55
-1.36 to 2.43
0.58
-1.34 to 2.58
0.48
-1.79 to 2.50
0.53
-1.45 to 2.42
0.50
-1.46 to 2.47
0.39
-1.85 to 2.38
0.37
-1.78 to 2.33
0.38
-1.71 to 2.29
0.35
-2.10 to 2.44
0.10
-2.13 to 2.10
0.03
-2.21 to 2.02
0.02
-2.09 to 1.97
-0.03
-2.23 to 1.96
EFPE_SC_6MG_QW-0.19
-0.95 to 0.57
-0.50
-1.23 to 0.27
EFPE_SC_4MG_QW-0.52
-2.33 to 1.31
1.26
-0.72 to 3.20
1.15
-0.92 to 3.10
1.00
-0.94 to 2.95
0.90
-1.20 to 2.82
0.90
-1.06 to 2.80
0.91
-1.04 to 2.81
0.90
-1.01 to 2.87
0.84
-1.40 to 2.83
0.74
-1.51 to 2.70
0.74
-1.15 to 2.61
0.79
-1.20 to 2.75
0.67
-1.55 to 2.69
0.72
-1.23 to 2.59
0.71
-1.24 to 2.64
0.58
-1.67 to 2.58
0.56
-1.55 to 2.50
0.58
-1.51 to 2.49
0.55
-1.89 to 2.64
0.30
-1.95 to 2.30
0.22
-1.96 to 2.22
0.21
-1.89 to 2.18
0.17
-1.96 to 2.12
0.19
-0.57 to 0.95
EFPE_SC_4MG_QW-0.29
-1.07 to 0.46
EFPE_SC_2MG_QW-0.21
-2.07 to 1.60
1.56
-0.43 to 3.54
1.45
-0.66 to 3.40
1.29
-0.69 to 3.27
1.20
-0.91 to 3.11
1.20
-0.79 to 3.09
1.22
-0.76 to 3.11
1.22
-0.73 to 3.16
1.14
-1.13 to 3.14
1.05
-1.21 to 3.04
1.04
-0.88 to 2.90
1.10
-0.87 to 3.04
0.98
-1.26 to 2.96
1.03
-0.93 to 2.90
1.01
-1.01 to 2.96
0.88
-1.37 to 2.85
0.87
-1.26 to 2.79
0.87
-1.25 to 2.82
0.85
-1.62 to 2.96
0.61
-1.68 to 2.60
0.52
-1.70 to 2.54
0.50
-1.59 to 2.47
0.48
-1.71 to 2.42
0.50
-0.27 to 1.23
0.29
-0.46 to 1.07
EFPE_SC_2MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.228 (95% CrI 0.016 to 0.706)
Residual deviance
43.1 for 43 data points
DIC
84.6 (pD 41.5)
Largest R-hat
1.006
Smallest ESS
bulk 578, tail 1,094
Divergent transitions
0
Convergence
All criteria met
Priors
PR01 N(0, 5^2); PR03 N(0, 2.5^2); PR07 half normal(0, 0.5^2) on tau

Frequentist check (netmeta)

Method
inverse variance, REML, MD
Tau
0.084
I squared
42%
Q (total)
6.94 on 4 df, P = 0.139
Q (between designs)
6.94, P = 0.139

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; 14 of 14
Background glucose lowering therapy (stratum S0 to S4)
effect modifier, prognostic factor; 14 of 14
Diabetes duration (years)
effect modifier, prognostic factor; 11 of 14
Asian ancestry or region (percent Asian)
effect modifier, prognostic factor; 10 of 14
Age (years)
prognostic factor; 14 of 14
Treatment duration (weeks)
effect modifier; 14 of 14
NCT03068065
S000048
9.12S0not reported100
region: all sites in Asia
47.1224
NCT00775684
S000051
6.54S03.89not reported55.1926.07
NCT00393718
S000330
9.27S08.24100
region: all sites in Asia
58.352
NCT03010683
S000389
8.5S0not reportednot reported50.526.07
NCT01558271
S000837
8.14S06.5998.9857.4752
SUSTAIN™1
S000878
8.05S04.221.453.7330
NCT01270191
S001002
12.35S0not reported100
region: all sites in Asia
53.1824
AWARD-CHN1
S001064
7.97S03.7797.6952.8426
NCT01733758
S001075
8.11S06.65not reported58.2552
NCT00676338
S001966
8.53S02.6712.44
Asian subgroup rows
53.826
AMPLITUDE-M
S002081
8.07S05.1not reported58.5156
NCT02505334
S002164
8.12S09.2810055.0126
S002947
S002947
8.55S047.4100
region: all sites in Asia
50.0420
S003108
S003108
9.2S08100
region: all sites in Asia
5824

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 HbA1c: design means range from 6.5 (EXEN_SC_10UG_BID vs GLIMEPIRIDE vs SITAGLIPTIN) to 12.3 (EXEN_SC_10UG_BID vs INS_NPH) percent; threshold 0.5
  • FlagBaseline, Diabetes duration: not reported by 3 of 14 trials
  • FlagBaseline, Diabetes duration: design means range from 2.7 (EXENER_SC_2MG_QW vs METFORMIN vs PIOGLITAZONE vs SITAGLIPTIN) to 47.4 (ECNO_SC_0p4MG_QW vs ECNO_SC_0p8MG_QW vs ECNO_SC_1p2MG_QW vs PLACEBO) years; threshold 3
  • FlagBaseline, Asian ancestry or region: not reported by 4 of 14 trials
  • FlagBaseline, Asian ancestry or region: design means range from 12.4 (EXENER_SC_2MG_QW vs METFORMIN vs PIOGLITAZONE vs SITAGLIPTIN) to 100.0 (ECNO_SC_0p4MG_QW vs ECNO_SC_0p8MG_QW vs ECNO_SC_1p2MG_QW vs PLACEBO) percent Asian; threshold 30
  • FlagBaseline, Age: design means range from 47.1 (GLICLAZIDE vs LIRA_SC_1p8MG_QD vs METFORMIN) to 58.5 (EFPE_SC_2MG_QW vs EFPE_SC_4MG_QW vs EFPE_SC_6MG_QW vs PLACEBO) years; threshold 10
  • FlagBaseline, Treatment duration: design means range from 20.0 (ECNO_SC_0p4MG_QW vs ECNO_SC_0p8MG_QW vs ECNO_SC_1p2MG_QW vs PLACEBO) to 56.0 (EFPE_SC_2MG_QW vs EFPE_SC_4MG_QW vs EFPE_SC_6MG_QW vs PLACEBO) weeks; threshold 26
  • NoteOutcome assessment, time point: selected time points span 20 to 30 weeks
  • NoteOutcome assessment, analysis set: mixed: completers 3, full_analysis 5, modified_itt 2, randomized 4
  • NoteRisk of bias, blinding: mixed: double_blind 8, open_label 4, single_blind 2
  • NoteRisk of bias, funding: mixed: industry 9, non_industry 3, not_reported 2
  • NoteData handling, input conversions: n_randomized 1
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)start yearblindingfundingEligibility
NCT0306806524completersnot statednot statednot statednot statednot statednot stated2014open_labelnot_reportedage 18 to 70; drug naive 3 months; HbA1c 7 to 14 percent; BMI 20 to 38; NAFLD on ultrasound
NCT0077568426.07completersnot statednot statednot statednot statednot statednot stated2008open_labelnon_industryage 18 to 70; fasting glucose 110 to 159 mg/dL off glucose lowering drugs; early T2D or impaired fasting glucose
NCT0039371824full_analysisnot statednot statednot statednot statednot statednot stated2006double_blindindustryage 20 or older; HbA1c 7.4 to 10.4 percent NGSP; with or without prior oral agents
NCT0301068326.07randomizednot statednot statednot statednot statednot statednot stated2015single_blindnot_reportednewly diagnosed treatment naive type 2 diabetes; no cardiovascular, liver or kidney disease
NCT0155827126full_analysisnot statednot statednot statednot statednot statednot stated2012double_blindindustryJapanese; age 20 or more; BMI 18.5 to 35; HbA1c 7.0 to 10.0 percent; OAM naive or OAM stopped
SUSTAIN™130full_analysisnot statednot statednot statednot statednot statednot stated2014double_blindindustryage 18 or older (20 in Japan); HbA1c 7.0 to 10.0 percent; drug naive on diet and exercise; eGFR 30 or more
NCT0127019126.07completersnot statednot statednot statednot statednot statednot stated2010open_labelnon_industryNewly diagnosed drug naive T2D, age 30 to 70, FPG above 300 mg/dL or HbA1c above 9
AWARD-CHN126modified_ittnot statednot statednot statednot statednot statednot stated2012double_blindindustryage 18 or older; BMI 19 to 35 kg/m2; HbA1c 7.0 to 10.5 percent OAM naive or 6.5 to 10.0 percent on OAM monotherapy
NCT0173375824modified_ittnot statednot statednot statednot statednot statednot stated2013double_blindindustryJapanese adults; diet and exercise with or without one oral drug; HbA1c 7 to 10 percent after washout
NCT0067633826full_analysisnot statednot statednot statednot statednot statednot stated2008double_blindindustryadults, HbA1c 7.1 to 11.0 percent, BMI 23 to 45 kg/m2, drug naive
AMPLITUDE-M30randomizednot statednot statednot statednot statednot statednot stated2017double_blindindustrytype 2 diabetes on diet and exercise, HbA1c 7 to 10 percent, no glucose lowering drug in prior 3 months
NCT0250533426full_analysisnot statednot statednot statednot statednot statednot stated2015open_labelindustryJapanese adults on one oral drug, HbA1c 7.5 to 10.0 percent; randomized if HbA1c 7.0 or more after run in
S00294720randomizednot statednot statednot statednot statednot statednot stated2021double_blindindustryage 18 to 65; HbA1c 7.0 to 10.5 percent; BMI 20 to 35; diet or one oral agent washed out
S00310824randomizednot statednot statednot statednot statednot statednot stated2012single_blindnon_industryT2D with coronary artery disease; no severe heart failure; creatinine up to 150 umol/L

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the mean difference on the analysis scale against the trial's first row. Flags mark converted, combined or approximated inputs.
Trial data entering this analysis
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
NCT03068065A1LIRA_SC_1p8MG_QD24arm, final5.9000.11029R0025051:Table 2
NCT03068065A2METFORMIN24arm, final6.0300.09029R0025051:Table 2
NCT03068065A3GLICLAZIDE24arm, final6.4700.17027R0025051:Table 2
NCT00775684A1EXEN_SC_10UG_BID26.07arm, change-0.2000.10014R0023972:Table 1
NCT00775684A2SITAGLIPTIN26.07arm, change-0.0100.10012R0023972:Table 1
NCT00775684A3GLIMEPIRIDE26.07arm, change-0.5000.20014R0023972:Table 1
NCT00393718A1LIRA_SC_0p9MG_QD24arm, final6.9900.070263registry:outcomes
NCT00393718A2GLIBENCLAMIDE24arm, final7.5000.090130registry:outcomes
NCT03010683A1LIRA_SC_1p8MG_QD26.07arm, final7.0000.21930R0016601:Table 2
NCT03010683A2METFORMIN26.07arm, final7.7000.18330R0016601:Table 2
NCT01558271A1DULA_SC_0p75MG_QW26arm, change-1.4300.050280R0011901:Results
NCT01558271A2LIRA_SC_0p9MG_QD26arm, change-1.3300.070136R0011901:Results
NCT01558271A3PLACEBO26arm, change0.1400.10068R0011901:Results
SUSTAIN™1A1SEMA_SC_0p5MG_QW30arm, change-1.4700.090128registry:outcomes
SUSTAIN™1A2SEMA_SC_1p0MG_QW30arm, change-1.5600.111130registry:outcomes
SUSTAIN™1A3PLACEBO30arm, change0.0000.079129registry:outcomes
NCT01270191A1INS_NPH26.07arm, final6.6000.23517R0012661:Table 2
NCT01270191A2EXEN_SC_10UG_BID26.07arm, final6.8800.19016R0012661:Table 2
AWARD-CHN1A1DULA_SC_1p5MG_QW26arm, change-1.4800.070239R0014229:Results
AWARD-CHN1A2DULA_SC_0p75MG_QW26arm, change-1.2200.070239R0014229:Results
AWARD-CHN1A3GLIMEPIRIDE26arm, change-0.9000.070245n_randomizedR0014229:Results
NCT01733758A1PLACEBO24arm, change0.2500.06877registry:outcomes
NCT01733758A2ALBI_SC_30MG_QW24arm, change-1.1000.047159registry:outcomes
NCT01733758A3ALBI_SC_50MG_QW24arm, change-1.3000.049150registry:outcomes
NCT01733758A4LIRA_SC_0p9MG_QD24arm, change-1.1900.063103registry:outcomes
NCT00676338A1EXENER_SC_2MG_QW26arm, change-1.5300.070218R0027761:Results
NCT00676338A2METFORMIN26arm, change-1.4800.070218R0027761:Results
NCT00676338A3PIOGLITAZONE26arm, change-1.6300.080137R0027761:Results
NCT00676338A4SITAGLIPTIN26arm, change-1.1500.080142R0027761:Results
AMPLITUDE-MA1EFPE_SC_2MG_QW30arm, change-1.1000.100100R0007136:Results
AMPLITUDE-MA2EFPE_SC_4MG_QW30arm, change-1.4000.100101R0007136:Results
AMPLITUDE-MA3EFPE_SC_6MG_QW30arm, change-1.6000.100103R0007136:Results
AMPLITUDE-MA4PLACEBO30arm, change-0.6001.200102R0007136:Results
NCT02505334A1LIRA_SC_1p8MG_QD26arm, change-0.2300.060233registry:outcomes
NCT02505334A2LIRA_SC_0p9MG_QD26arm, change0.1700.060233registry:outcomes
S002947A1ECNO_SC_0p4MG_QW20arm, change-1.8100.15033R0006482:Results
S002947A2ECNO_SC_0p8MG_QW20arm, change-1.9000.15031R0006482:Results
S002947A3ECNO_SC_1p2MG_QW20arm, change-2.3900.15032R0006482:Results
S002947A4PLACEBO20arm, change-0.5500.15033R0006482:Results
S003108A1LIRA_SC_FLEX_0p6-1p2-1p8_QD24arm, final6.8000.14630R0025278:Table 2
S003108A2METFORMIN24arm, final6.9000.12830R0025278:Table 2
S003108A3LIRA_SC_1p8MG_QD24arm, final6.8000.16430R0025278:Table 2
S003108A4LIRAMETF_SC_1p2-1500MG_QD24arm, final6.7000.12830R0025278:Table 2

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