LivingGLP1
Network meta-analysis

Body weight change in kilograms (diabetes)

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
10
Randomized trials
20
Treatments
3,238
Participants
31
Trial arms

In plain language

Across 10 trials with 3,238 participants, 0 of 19 treatments had a clearly better result than placebo on body weight change in kilograms (diabetes), and for 19 the evidence could not tell them apart from placebo. The most favorable estimate was for Metformin: mean difference -5.02 kg (95% credible interval -10.60 to 2.91).

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_QWECNO_SC_0p4MG_QWEFPE_SC_2MG_QWEFPE_SC_4MG_QWEFPE_SC_6MG_QWEXENER_SC_2MG_QWGLIBENCLAMIDEGLICLAZIDELIRA_SC_0p9MG_QDLIRA_SC_1p8MG_QDMETFORMINPIOGLITAZONEPLACEBOSEMA_PO_14MG_QDSEMA_PO_3MG_QDSEMA_PO_7MG_QDSEMA_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 kg. Lower values favor the treatment.
-15-10-5051015← favors treatmentfavors reference →MetforminExenatide extended release 2 mg …SitagliptinSemaglutide 1.0 mg subcutaneous …Semaglutide 0.5 mg subcutaneous …Efpeglenatide 4 mg subcutaneous …Efpeglenatide 6 mg subcutaneous …Ecnoglutide 0.4 mg injection onc…PioglitazoneSemaglutide 14 mg oral once dail…Semaglutide 7 mg oral once daily…Efpeglenatide 2 mg subcutaneous …Semaglutide 3 mg oral once daily…Albiglutide 50 mg subcutaneous o…Liraglutide 0.9 mg injection onc…Albiglutide 30 mg subcutaneous o…Liraglutide 1.8 mg subcutaneous …GlibenclamideGliclazide
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
Metformin
METFORMIN
-5.02 (-10.60 to 2.91)-11.74 to 4.65-7.87 (-13.19 to -2.56)Unclear
Exenatide extended release 2 mg subcutaneous once weekly
EXENER_SC_2MG_QW
-4.99 (-11.33 to 4.22)-12.11 to 5.65-7.87 (-13.41 to -2.34)Unclear
Sitagliptin
SITAGLIPTIN
-3.80 (-10.17 to 5.35)-11.05 to 6.63-6.67 (-12.23 to -1.12)Unclear
Semaglutide 1.0 mg subcutaneous once weekly
SEMA_SC_1p0MG_QW
-3.69 (-7.99 to 1.27)-9.75 to 3.15-3.78 (-5.58 to -1.98)Unclear
Semaglutide 0.5 mg subcutaneous once weekly
SEMA_SC_0p5MG_QW
-2.73 (-6.95 to 2.16)-9.02 to 4.06-2.79 (-4.50 to -1.08)Unclear
Efpeglenatide 4 mg subcutaneous once weekly
EFPE_SC_4MG_QW
-2.22 (-6.60 to 2.37)-8.21 to 4.67-2.30 (-4.40 to -0.20)Unclear
Efpeglenatide 6 mg subcutaneous once weekly
EFPE_SC_6MG_QW
-2.14 (-6.59 to 2.64)-8.46 to 4.57-2.20 (-4.20 to -0.20)Unclear
Ecnoglutide 0.4 mg injection once weekly
ECNO_SC_0p4MG_QW
-2.03 (-6.44 to 2.58)-8.37 to 4.51-2.07 (-3.75 to -0.39)Unclear
Pioglitazone
PIOGLITAZONE
-1.53 (-7.83 to 7.48)-8.79 to 8.84-4.37 (-9.93 to 1.18)Unclear
Semaglutide 14 mg oral once daily (original tablet)
SEMA_PO_14MG_QD
-1.38 (-5.12 to 3.27)-7.18 to 5.39-1.56 (-3.20 to 0.08)Unclear
Semaglutide 7 mg oral once daily (original tablet)
SEMA_PO_7MG_QD
-0.22 (-3.99 to 4.35)-5.92 to 6.65-0.36 (-1.86 to 1.14)Unclear
Efpeglenatide 2 mg subcutaneous once weekly
EFPE_SC_2MG_QW
0.44 (-3.91 to 4.94)-5.74 to 7.370.40 (-1.60 to 2.40)Unclear
Semaglutide 3 mg oral once daily (original tablet)
SEMA_PO_3MG_QD
0.60 (-3.10 to 5.16)-5.02 to 7.370.44 (-1.06 to 1.94)Unclear
Albiglutide 50 mg subcutaneous once weekly
ALBI_SC_50MG_QW
0.85 (-2.91 to 5.34)-4.85 to 7.680.71 (-0.72 to 2.13)Unclear
Liraglutide 0.9 mg injection once daily
LIRA_SC_0p9MG_QD
1.04 (-1.13 to 5.23)-3.51 to 7.900.68 (-0.43 to 1.79)Unclear
Albiglutide 30 mg subcutaneous once weekly
ALBI_SC_30MG_QW
1.22 (-2.39 to 5.88)-4.68 to 8.161.07 (-0.35 to 2.49)Unclear
Liraglutide 1.8 mg subcutaneous once daily
LIRA_SC_1p8MG_QD
1.84 (-1.19 to 9.55)-2.70 to 11.400.86 (-1.00 to 2.72)Unclear
Glibenclamide
GLIBENCLAMIDE
2.94 (-1.23 to 9.93)-2.61 to 11.672.59 (0.71 to 4.47)Unclear
Gliclazide
GLICLAZIDE
3.21 (-4.05 to 12.50)-4.90 to 13.961.18 (-5.42 to 7.79)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 columnPLACEBOMETFORMINEXENER_SC_2MG_QWSITAGLIPTINSEMA_SC_1p0MG_QWSEMA_SC_0p5MG_QWEFPE_SC_4MG_QWEFPE_SC_6MG_QWECNO_SC_0p4MG_QWPIOGLITAZONESEMA_PO_14MG_QDSEMA_PO_7MG_QDEFPE_SC_2MG_QWSEMA_PO_3MG_QDALBI_SC_50MG_QWLIRA_SC_0p9MG_QDALBI_SC_30MG_QWLIRA_SC_1p8MG_QDGLIBENCLAMIDEGLICLAZIDE
PLACEBOPLACEBO5.02
-2.91 to 10.60
4.99
-4.22 to 11.33
3.80
-5.35 to 10.17
3.69
-1.27 to 7.99
2.73
-2.16 to 6.95
2.22
-2.37 to 6.60
2.14
-2.64 to 6.59
2.03
-2.58 to 6.44
1.53
-7.48 to 7.83
1.38
-3.27 to 5.12
0.22
-4.35 to 3.99
-0.44
-4.94 to 3.91
-0.60
-5.16 to 3.10
-0.85
-5.34 to 2.91
-1.04
-5.23 to 1.13
-1.22
-5.88 to 2.39
-1.84
-9.55 to 1.19
-2.94
-9.93 to 1.23
-3.21
-12.50 to 4.05
METFORMIN-5.02
-10.60 to 2.91
METFORMIN-0.07
-4.74 to 4.32
-1.25
-5.77 to 3.21
-1.48
-8.12 to 8.33
-2.39
-9.15 to 6.94
-2.93
-9.60 to 6.68
-3.01
-9.74 to 6.64
-3.09
-9.79 to 6.22
-3.55
-8.11 to 0.91
-3.78
-10.29 to 4.67
-4.91
-11.37 to 3.82
-5.53
-12.13 to 3.74
-5.76
-12.30 to 2.96
-6.04
-12.37 to 2.64
-6.23
-11.88 to 0.73
-6.42
-12.63 to 2.12
-7.28
-12.68 to -2.01
-8.30
-15.04 to 0.16
-8.19
-15.58 to -0.64
EXENER_SC_2MG_QW-4.99
-11.33 to 4.22
0.07
-4.32 to 4.74
EXENER_SC_2MG_QW-1.19
-5.53 to 3.26
-1.42
-8.85 to 9.14
-2.31
-9.67 to 8.15
-2.82
-10.24 to 7.74
-2.92
-10.20 to 7.52
-3.01
-10.40 to 7.29
-3.50
-7.93 to 1.35
-3.71
-10.77 to 5.92
-4.85
-11.93 to 4.85
-5.52
-12.72 to 4.89
-5.75
-12.71 to 3.97
-5.98
-13.13 to 3.71
-6.15
-12.67 to 1.91
-6.30
-13.40 to 3.30
-7.13
-14.03 to -0.57
-8.21
-15.69 to 1.20
-8.11
-16.41 to 0.25
SITAGLIPTIN-3.80
-10.17 to 5.35
1.25
-3.21 to 5.77
1.19
-3.26 to 5.53
SITAGLIPTIN-0.22
-7.69 to 10.26
-1.16
-8.61 to 9.20
-1.66
-9.02 to 8.72
-1.79
-8.94 to 8.71
-1.83
-9.06 to 8.42
-2.28
-6.83 to 2.30
-2.53
-9.65 to 7.27
-3.65
-10.60 to 5.85
-4.33
-11.54 to 6.11
-4.53
-11.47 to 5.03
-4.77
-11.73 to 4.88
-4.98
-11.34 to 3.06
-5.11
-12.04 to 4.41
-6.03
-12.62 to 0.56
-6.97
-14.41 to 2.09
-6.92
-15.18 to 1.36
SEMA_SC_1p0MG_QW-3.69
-7.99 to 1.27
1.48
-8.33 to 8.12
1.42
-9.14 to 8.85
0.22
-10.26 to 7.69
SEMA_SC_1p0MG_QW-0.96
-5.60 to 3.63
-1.46
-7.75 to 4.99
-1.54
-8.01 to 5.12
-1.65
-7.77 to 4.76
-2.05
-12.42 to 5.36
-2.30
-8.61 to 3.47
-3.49
-9.79 to 2.64
-4.09
-10.63 to 2.30
-4.33
-10.48 to 1.74
-4.54
-11.07 to 1.51
-4.73
-11.17 to 0.08
-4.92
-11.32 to 0.86
-5.48
-14.63 to -0.70
-6.67
-14.90 to -0.36
-6.80
-17.42 to 1.53
SEMA_SC_0p5MG_QW-2.73
-6.95 to 2.16
2.39
-6.94 to 9.15
2.31
-8.15 to 9.67
1.16
-9.20 to 8.61
0.96
-3.63 to 5.60
SEMA_SC_0p5MG_QW-0.52
-6.88 to 5.95
-0.56
-7.17 to 6.02
-0.70
-6.98 to 5.96
-1.11
-11.47 to 6.30
-1.37
-7.76 to 4.73
-2.52
-8.78 to 3.52
-3.14
-9.52 to 3.33
-3.34
-9.66 to 2.58
-3.61
-10.06 to 2.52
-3.77
-9.85 to 0.99
-3.95
-10.17 to 1.93
-4.54
-13.59 to 0.13
-5.71
-13.61 to 0.45
-5.87
-16.55 to 2.43
EFPE_SC_4MG_QW-2.22
-6.60 to 2.37
2.93
-6.68 to 9.60
2.82
-7.74 to 10.24
1.66
-8.72 to 9.02
1.46
-4.99 to 7.75
0.52
-5.95 to 6.88
EFPE_SC_4MG_QW-0.08
-4.85 to 4.67
-0.21
-6.60 to 6.65
-0.67
-10.90 to 6.69
-0.88
-7.13 to 5.03
-2.02
-8.19 to 3.84
-2.65
-7.29 to 2.14
-2.85
-9.03 to 2.87
-3.13
-9.61 to 2.79
-3.29
-9.58 to 1.43
-3.50
-9.74 to 2.52
-4.09
-13.14 to 0.71
-5.22
-13.51 to 0.73
-5.33
-15.81 to 2.65
EFPE_SC_6MG_QW-2.14
-6.59 to 2.64
3.01
-6.64 to 9.74
2.92
-7.52 to 10.20
1.79
-8.71 to 8.94
1.54
-5.12 to 8.01
0.56
-6.02 to 7.17
0.08
-4.67 to 4.85
EFPE_SC_6MG_QW-0.11
-6.51 to 6.59
-0.54
-10.94 to 6.78
-0.78
-7.32 to 5.11
-1.96
-8.25 to 4.03
-2.57
-7.34 to 2.20
-2.77
-9.11 to 2.96
-3.00
-9.57 to 2.70
-3.18
-9.62 to 1.42
-3.35
-9.90 to 2.54
-3.97
-13.38 to 0.58
-5.15
-13.38 to 0.61
-5.25
-15.91 to 2.84
ECNO_SC_0p4MG_QW-2.03
-6.44 to 2.58
3.09
-6.22 to 9.79
3.01
-7.29 to 10.40
1.83
-8.42 to 9.06
1.65
-4.76 to 7.77
0.70
-5.96 to 6.98
0.21
-6.65 to 6.60
0.11
-6.59 to 6.51
ECNO_SC_0p4MG_QW-0.44
-10.81 to 6.80
-0.66
-7.24 to 5.02
-1.83
-8.26 to 4.15
-2.49
-8.87 to 3.76
-2.66
-9.22 to 3.14
-2.90
-9.30 to 2.71
-3.07
-9.62 to 1.45
-3.26
-9.75 to 2.57
-3.84
-13.19 to 0.69
-5.00
-13.22 to 0.56
-5.17
-15.70 to 2.90
PIOGLITAZONE-1.53
-7.83 to 7.48
3.55
-0.91 to 8.11
3.50
-1.35 to 7.93
2.28
-2.30 to 6.83
2.05
-5.36 to 12.42
1.11
-6.30 to 11.47
0.67
-6.69 to 10.90
0.54
-6.78 to 10.94
0.44
-6.80 to 10.81
PIOGLITAZONE-0.24
-7.27 to 9.24
-1.43
-8.31 to 7.92
-2.01
-9.26 to 8.30
-2.23
-9.17 to 7.22
-2.48
-9.52 to 6.91
-2.71
-9.08 to 5.21
-2.85
-9.80 to 6.63
-3.70
-10.39 to 2.68
-4.72
-12.29 to 4.45
-4.62
-13.09 to 3.89
SEMA_PO_14MG_QD-1.38
-5.12 to 3.27
3.78
-4.67 to 10.29
3.71
-5.92 to 10.77
2.53
-7.27 to 9.65
2.30
-3.47 to 8.61
1.37
-4.73 to 7.76
0.88
-5.03 to 7.13
0.78
-5.11 to 7.32
0.66
-5.02 to 7.24
0.24
-9.24 to 7.27
SEMA_PO_14MG_QD-1.18
-5.87 to 3.57
-1.79
-7.47 to 4.69
-2.00
-6.73 to 2.67
-2.24
-7.96 to 3.67
-2.42
-7.26 to 1.36
-2.59
-8.09 to 3.04
-3.16
-11.08 to 0.99
-4.36
-11.77 to 1.49
-4.43
-14.25 to 3.53
SEMA_PO_7MG_QD-0.22
-3.99 to 4.35
4.91
-3.82 to 11.37
4.85
-4.85 to 11.93
3.65
-5.85 to 10.60
3.49
-2.64 to 9.79
2.52
-3.52 to 8.78
2.02
-3.84 to 8.19
1.96
-4.03 to 8.25
1.83
-4.15 to 8.26
1.43
-7.92 to 8.31
1.18
-3.57 to 5.87
SEMA_PO_7MG_QD-0.62
-6.41 to 5.55
-0.81
-5.62 to 3.71
-1.08
-6.94 to 4.63
-1.22
-6.23 to 2.43
-1.43
-6.85 to 4.13
-2.00
-10.29 to 2.02
-3.16
-10.68 to 2.34
-3.28
-13.38 to 4.48
EFPE_SC_2MG_QW0.44
-3.91 to 4.94
5.53
-3.74 to 12.13
5.52
-4.89 to 12.72
4.33
-6.11 to 11.54
4.09
-2.30 to 10.63
3.14
-3.33 to 9.52
2.65
-2.14 to 7.29
2.57
-2.20 to 7.34
2.49
-3.76 to 8.87
2.01
-8.30 to 9.26
1.79
-4.69 to 7.47
0.62
-5.55 to 6.41
EFPE_SC_2MG_QW-0.20
-6.59 to 5.36
-0.45
-6.85 to 5.44
-0.63
-6.72 to 3.92
-0.82
-7.24 to 5.08
-1.43
-10.47 to 3.06
-2.53
-10.68 to 3.20
-2.66
-13.27 to 5.34
SEMA_PO_3MG_QD0.60
-3.10 to 5.16
5.76
-2.96 to 12.30
5.75
-3.97 to 12.71
4.53
-5.03 to 11.47
4.33
-1.74 to 10.48
3.34
-2.58 to 9.66
2.85
-2.87 to 9.03
2.77
-2.96 to 9.11
2.66
-3.14 to 9.22
2.23
-7.22 to 9.17
2.00
-2.67 to 6.73
0.81
-3.71 to 5.62
0.20
-5.36 to 6.59
SEMA_PO_3MG_QD-0.26
-5.96 to 5.48
-0.42
-5.43 to 3.36
-0.60
-6.20 to 4.81
-1.14
-9.31 to 3.06
-2.34
-9.42 to 3.21
-2.43
-12.28 to 5.33
ALBI_SC_50MG_QW0.85
-2.91 to 5.34
6.04
-2.64 to 12.37
5.98
-3.71 to 13.13
4.77
-4.88 to 11.73
4.54
-1.51 to 11.07
3.61
-2.52 to 10.06
3.13
-2.79 to 9.61
3.00
-2.70 to 9.57
2.90
-2.71 to 9.30
2.48
-6.91 to 9.52
2.24
-3.67 to 7.96
1.08
-4.63 to 6.94
0.45
-5.44 to 6.85
0.26
-5.48 to 5.96
ALBI_SC_50MG_QW-0.16
-5.07 to 3.52
-0.35
-4.89 to 4.17
-0.89
-9.00 to 2.99
-2.09
-9.17 to 3.31
-2.21
-12.20 to 5.68
LIRA_SC_0p9MG_QD1.04
-1.13 to 5.23
6.23
-0.73 to 11.88
6.15
-1.91 to 12.67
4.98
-3.06 to 11.34
4.73
-0.08 to 11.17
3.77
-0.99 to 9.85
3.29
-1.43 to 9.58
3.18
-1.42 to 9.62
3.07
-1.45 to 9.62
2.71
-5.21 to 9.08
2.42
-1.36 to 7.26
1.22
-2.43 to 6.23
0.63
-3.92 to 6.72
0.42
-3.36 to 5.43
0.16
-3.52 to 5.07
LIRA_SC_0p9MG_QD-0.23
-3.90 to 4.70
-0.73
-6.66 to 2.19
-1.93
-6.87 to 2.35
-2.02
-10.68 to 5.35
ALBI_SC_30MG_QW1.22
-2.39 to 5.88
6.42
-2.12 to 12.63
6.30
-3.30 to 13.40
5.11
-4.41 to 12.04
4.92
-0.86 to 11.32
3.95
-1.93 to 10.17
3.50
-2.52 to 9.74
3.35
-2.54 to 9.90
3.26
-2.57 to 9.75
2.85
-6.63 to 9.80
2.59
-3.04 to 8.09
1.43
-4.13 to 6.85
0.82
-5.08 to 7.24
0.60
-4.81 to 6.20
0.35
-4.17 to 4.89
0.23
-4.70 to 3.90
ALBI_SC_30MG_QW-0.53
-8.75 to 3.40
-1.74
-8.91 to 3.55
-1.80
-11.85 to 5.85
LIRA_SC_1p8MG_QD1.84
-1.19 to 9.55
7.28
2.01 to 12.68
7.13
0.57 to 14.03
6.03
-0.56 to 12.62
5.48
0.70 to 14.63
4.54
-0.13 to 13.59
4.09
-0.71 to 13.14
3.97
-0.58 to 13.38
3.84
-0.69 to 13.19
3.70
-2.68 to 10.39
3.16
-0.99 to 11.08
2.00
-2.02 to 10.29
1.43
-3.06 to 10.47
1.14
-3.06 to 9.31
0.89
-2.99 to 9.00
0.73
-2.19 to 6.66
0.53
-3.40 to 8.75
LIRA_SC_1p8MG_QD-1.26
-6.01 to 6.54
-0.89
-7.95 to 6.10
GLIBENCLAMIDE2.94
-1.23 to 9.93
8.30
-0.16 to 15.04
8.21
-1.20 to 15.69
6.97
-2.09 to 14.41
6.67
0.36 to 14.90
5.71
-0.45 to 13.61
5.22
-0.73 to 13.51
5.15
-0.61 to 13.38
5.00
-0.56 to 13.22
4.72
-4.45 to 12.29
4.36
-1.49 to 11.77
3.16
-2.34 to 10.68
2.53
-3.20 to 10.68
2.34
-3.21 to 9.42
2.09
-3.31 to 9.17
1.93
-2.35 to 6.87
1.74
-3.55 to 8.91
1.26
-6.54 to 6.01
GLIBENCLAMIDE0.04
-9.77 to 8.45
GLICLAZIDE3.21
-4.05 to 12.50
8.19
0.64 to 15.58
8.11
-0.25 to 16.41
6.92
-1.36 to 15.18
6.80
-1.53 to 17.42
5.87
-2.43 to 16.55
5.33
-2.65 to 15.81
5.25
-2.84 to 15.91
5.17
-2.90 to 15.70
4.62
-3.89 to 13.09
4.43
-3.53 to 14.25
3.28
-4.48 to 13.38
2.66
-5.34 to 13.27
2.43
-5.33 to 12.28
2.21
-5.68 to 12.20
2.02
-5.35 to 10.68
1.80
-5.85 to 11.85
0.89
-6.10 to 7.95
-0.04
-8.45 to 9.77
GLICLAZIDE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
1.520 (95% CrI 0.164 to 4.690)
Residual deviance
32.4 for 30 data points
DIC
61.4 (pD 29.0)
Largest R-hat
1.003
Smallest ESS
bulk 893, tail 2,034
Divergent transitions
0
Convergence
All criteria met
Priors
PR01 N(0, 25^2); PR03 N(0, 12.5^2); PR07 half normal(0, 2.5^2) on tau

Frequentist check (netmeta)

Method
inverse variance, REML, MD
Tau
0.734
I squared
79%
Q (total)
9.68 on 2 df, P = 0.008
Q (between designs)
9.68, P = 0.008

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; 10 of 10
Sex (percent female)
effect modifier, prognostic factor; 9 of 10
Background glucose lowering therapy (stratum S0 to S4)
effect modifier, prognostic factor; 10 of 10
Asian ancestry or region (percent Asian)
effect modifier, prognostic factor; 7 of 10
Kidney function (eGFR) (mL/min/1.73 m2)
prognostic factor, effect modifier; 4 of 10
Treatment duration (weeks)
effect modifier; 10 of 10
Lifestyle co-intervention intensity (none standard intensive)
effect modifier, prognostic factor; 10 of 10
NCT03068065
S000048
27.4627.96S0100
region: all sites in Asia
not reported24standard
NCT00393718
S000330
24.832.75S0100
region: all sites in Asia
not reported52not_reported
NCT03010683
S000389
30.333.33S0not reported8426.07not_reported
SUSTAIN™1
S000878
33.245.62S021.495.630not_reported
NCT01733758
S001075
25.82not reportedS0not reportednot reported52not_reported
PIONEER 9
S001943
25.921.4S01009752not_reported
NCT00676338
S001966
31.2140.99S012.44
Asian subgroup rows
not reported26standard
AMPLITUDE-M
S002081
34.246.06S0not reported101.2456not_reported
NCT02505334
S002164
27.2731.1S0100not reported26not_reported
S002947
S002947
26.2535.85S0100
region: all sites in Asia
not reported20not_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: design means range from 24.8 (GLIBENCLAMIDE vs LIRA_SC_0p9MG_QD) to 34.2 (EFPE_SC_2MG_QW vs EFPE_SC_4MG_QW vs EFPE_SC_6MG_QW vs PLACEBO) kg/m2; threshold 3
  • FlagBaseline, Sex: design means range from 21.4 (LIRA_SC_0p9MG_QD vs PLACEBO vs SEMA_PO_14MG_QD vs SEMA_PO_3MG_QD vs SEMA_PO_7MG_QD) to 46.1 (EFPE_SC_2MG_QW vs EFPE_SC_4MG_QW vs EFPE_SC_6MG_QW vs PLACEBO) percent female; threshold 15
  • FlagBaseline, Asian ancestry or region: not reported by 3 of 10 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 PLACEBO) percent Asian; threshold 30
  • FlagBaseline, Kidney function (eGFR): not reported by 6 of 10 trials
  • FlagBaseline, Kidney function (eGFR): design means range from 84.0 (LIRA_SC_1p8MG_QD vs METFORMIN) to 101.2 (EFPE_SC_2MG_QW vs EFPE_SC_4MG_QW vs EFPE_SC_6MG_QW vs PLACEBO) mL/min/1.73 m2; threshold 15
  • FlagBaseline, Treatment duration: design means range from 20.0 (ECNO_SC_0p4MG_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 1, full_analysis 5, modified_itt 1, randomized 3
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 1, not stated 9
  • NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 1, not stated 9
  • NoteRisk of bias, blinding: mixed: double_blind 7, open_label 2, single_blind 1
  • NoteRisk of bias, funding: mixed: industry 8, not_reported 2
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
NCT0306806524completersnot statednot statednot statednot statednot statednot statedopen_labelnot_reported2014age 18 to 70; drug naive 3 months; HbA1c 7 to 14 percent; BMI 20 to 38; NAFLD on ultrasound
NCT0039371824full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2006age 20 or older; HbA1c 7.4 to 10.4 percent NGSP; with or without prior oral agents
NCT0301068326.07randomizednot statednot statednot statednot statednot statednot statedsingle_blindnot_reported2015newly diagnosed treatment naive type 2 diabetes; no cardiovascular, liver or kidney disease
SUSTAIN™130full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2014age 18 or older (20 in Japan); HbA1c 7.0 to 10.0 percent; drug naive on diet and exercise; eGFR 30 or more
NCT0173375824modified_ittnot 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 926full_analysisnot statednot statednot statednot statedhypotheticalhypotheticaldouble_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
NCT0067633826full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2008adults, HbA1c 7.1 to 11.0 percent, BMI 23 to 45 kg/m2, drug naive
AMPLITUDE-M30randomizednot 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
NCT0250533426full_analysisnot statednot statednot statednot statednot statednot statedopen_labelindustry2015Japanese 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 stateddouble_blindindustry2021age 18 to 65; HbA1c 7.0 to 10.5 percent; BMI 20 to 35; diet or one oral agent washed out

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, final75.5002.00029R0025051:Table 1
NCT03068065A2METFORMIN24arm, final71.2002.55029R0025051:Table 1
NCT03068065A3GLICLAZIDE24arm, final77.5402.57027R0025051:Table 1
NCT00393718A1LIRA_SC_0p9MG_QD24arm, final64.0600.150265registry:outcomes
NCT00393718A2GLIBENCLAMIDE24arm, final65.9700.200130registry:outcomes
NCT03010683A1LIRA_SC_1p8MG_QD26.07arm, final92.0002.92130R0016601:Table 2
NCT03010683A2METFORMIN26.07arm, final77.0002.55630R0016601:Table 2
SUSTAIN™1A1SEMA_SC_0p5MG_QW30arm, change-3.6800.356128registry:outcomes
SUSTAIN™1A2SEMA_SC_1p0MG_QW30arm, change-4.6700.455130registry:outcomes
SUSTAIN™1A3PLACEBO30arm, change-0.8900.305129registry:outcomes
NCT01733758A1PLACEBO24arm, change-0.5000.19477registry:outcomes
NCT01733758A2ALBI_SC_30MG_QW24arm, change0.3200.142159registry:outcomes
NCT01733758A3ALBI_SC_50MG_QW24arm, change-0.0400.161150registry:outcomes
NCT01733758A4LIRA_SC_0p9MG_QD24arm, change-0.3400.255103registry:outcomes
PIONEER 9A1SEMA_PO_3MG_QD26arm, change-0.4000.27149registry:outcomes
PIONEER 9A2SEMA_PO_7MG_QD26arm, change-1.2000.27149registry:outcomes
PIONEER 9A3SEMA_PO_14MG_QD26arm, change-2.4000.43348registry:outcomes
PIONEER 9A4LIRA_SC_0p9MG_QD26arm, change0.1000.23148registry:outcomes
PIONEER 9A5PLACEBO26arm, change-1.1000.22949registry:outcomes
NCT00676338A1EXENER_SC_2MG_QW26arm, change-2.0000.200215R0027761:Results
NCT00676338A2METFORMIN26arm, change-2.0000.200217R0027761:Results
NCT00676338A3PIOGLITAZONE26arm, change1.5000.300134R0027761:Results
NCT00676338A4SITAGLIPTIN26arm, change-0.8000.300141R0027761:Results
AMPLITUDE-MA1EFPE_SC_2MG_QW30arm, change-0.8000.500100R0007136:Figure 2
AMPLITUDE-MA2EFPE_SC_4MG_QW30arm, change-3.5000.600101R0007136:Figure 2
AMPLITUDE-MA3EFPE_SC_6MG_QW30arm, change-3.4000.500103R0007136:Figure 2
AMPLITUDE-MA4PLACEBO30arm, change-1.2000.500102R0007136:Figure 2
NCT02505334A1LIRA_SC_1p8MG_QD26arm, change-0.7700.132233R0022075:Results
NCT02505334A2LIRA_SC_0p9MG_QD26arm, change-0.9500.143233R0022075:Results
S002947A1ECNO_SC_0p4MG_QW20contrast, md-2.0700.439R0006482:Figure 4
S002947A4PLACEBO20contrast, mdR0006482:Figure 4

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