LivingGLP1
Network meta-analysis

Body weight change in kilograms (diabetes)

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 pooledMean difference
23
Randomized trials
15
Treatments
13,888
Participants
50
Trial arms

In plain language

Across 23 trials with 13,888 participants, 9 of 14 treatments had a clearly better result than placebo on body weight change in kilograms (diabetes), and for 5 the evidence could not tell them apart from placebo. The most favorable estimate was for tirzepatide injection: mean difference -5.95 kg (95% credible interval -7.44 to -4.37).

  • Tirzepatide injection: among the most effective (certainty pending).
  • Semaglutide injection: among the most effective (certainty pending).
  • Exenatide extended release and dapagliflozin injection: better than placebo but not among the most effective (certainty pending).
  • Semaglutide tablet: among the most effective (certainty pending).
  • Empagliflozin: better than placebo but not among the most effective (certainty pending).
  • Dapagliflozin: not convincingly different from placebo (certainty pending).
  • Exenatide injection: better than placebo but not among the most effective (certainty pending).
  • Liraglutide injection: better than placebo but not among the most effective (certainty pending).
  • Exenatide extended release injection: not convincingly different from placebo (certainty pending).
  • Lixisenatide injection: better than placebo but not among the most effective (certainty pending).
  • Dulaglutide injection: better than placebo but not among the most effective (certainty pending).
  • Sitagliptin: not convincingly different from placebo (certainty pending).
  • Insulin glargine with lixisenatide injection: not convincingly different from placebo (certainty pending).
  • Insulin glargine: not convincingly different from placebo (certainty pending).

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.
DAPAEXEN_SCDAPAGLIFLOZINDULA_SCEMPAGLIFLOZINEXENER_SCEXEN_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

Mean difference in kg. Lower values favor the treatment.
-8-6-4-202← favors treatmentfavors reference →Tirzepatide injectionSemaglutide injectionExenatide extended release and d…Semaglutide tabletEmpagliflozinDapagliflozinExenatide injectionLiraglutide injectionExenatide extended release injec…Lixisenatide injectionDulaglutide injectionSitagliptinInsulin glargine with lixisenati…Insulin glargine
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)VerdictConfidence
Tirzepatide injection
TIRZ_SC
-5.95 (-7.44 to -4.37)-8.16 to -3.60-6.00 (-7.37 to -4.63)Betterpending
Semaglutide injection
SEMA_SC
-3.39 (-4.62 to -2.14)-5.45 to -1.25-3.40 (-4.49 to -2.31)Betterpending
Exenatide extended release and dapagliflozin injection
DAPAEXEN_SC
-3.34 (-6.33 to -0.34)-6.75 to 0.15-3.47 (-6.13 to -0.81)Betterpending
Semaglutide tablet
SEMA_PO
-2.68 (-3.80 to -1.61)-4.74 to -0.71-2.71 (-3.64 to -1.77)Betterpending
Empagliflozin
EMPAGLIFLOZIN
-2.27 (-4.38 to -0.23)-4.96 to 0.33-2.31 (-4.06 to -0.55)Betterpending
Dapagliflozin
DAPAGLIFLOZIN
-2.01 (-5.05 to 0.90)-5.42 to 1.36-2.14 (-4.79 to 0.52)Unclearpending
Exenatide injection
EXEN_SC
-1.99 (-3.56 to -0.35)-4.24 to 0.37-2.03 (-3.44 to -0.61)Betterpending
Liraglutide injection
LIRA_SC
-1.69 (-2.67 to -0.71)-3.58 to 0.28-1.70 (-2.55 to -0.85)Betterpending
Exenatide extended release injection
EXENER_SC
-1.40 (-3.77 to 1.03)-4.27 to 1.57-1.48 (-3.61 to 0.66)Unclearpending
Lixisenatide injection
LIXI_SC
-1.27 (-2.49 to -0.03)-3.33 to 0.80-1.28 (-2.36 to -0.20)Betterpending
Dulaglutide injection
DULA_SC
-1.12 (-1.95 to -0.31)-2.98 to 0.69-1.12 (-1.84 to -0.41)Betterpending
Sitagliptin
SITAGLIPTIN
-0.37 (-1.48 to 0.74)-2.30 to 1.68-0.39 (-1.33 to 0.55)Unclearpending
Insulin glargine with lixisenatide injection
IGLARLIXI_SC
0.21 (-1.43 to 1.80)-2.10 to 2.560.21 (-1.18 to 1.61)Unclearpending
Insulin glargine
INS_GLARGINE
1.12 (-0.22 to 2.42)-1.05 to 3.271.14 (0.00 to 2.27)Unclearpending

Confidence in the results

How much each comparison can be trusted, rated with CINeMA in six domains and summarized with GRADE.
Confidence in each comparison with Placebo
ComparisonWithin study biasReporting biasIndirectnessImprecisionHeterogeneityIncoherenceConfidence
Exenatide extended release and dapagliflozin injection versus Placebopendingsomependingsomenonesomepending
Dapagliflozin versus Placebopendingsomependingsomenonesomepending
Dulaglutide injection versus Placebopendingsomependingnonesomenonepending
Empagliflozin versus Placebopendingsomependingsomenonesomepending
Exenatide injection versus Placebopendingsomependingsomenonesomepending
Exenatide extended release injection versus Placebopendingsomependingsomenonesomepending
Insulin glargine with lixisenatide injection versus Placebopendingsomependingnonemajorsomepending
Insulin glargine versus Placebopendingsomependingsomenonesomepending
Liraglutide injection versus Placebopendingsomependingsomenonenonepending
Lixisenatide injection versus Placebopendingsomependingsomenonesomepending
Semaglutide tablet versus Placebopendingsomependingsomenonesomepending
Semaglutide injection versus Placebopendingsomependingnonesomesomepending
Sitagliptin versus Placebopendingsomependingnonesomesomepending
Tirzepatide injection versus Placebopendingsomependingnonenonesomepending
Every other comparison (91)
Confidence in the other comparisons
ComparisonWithin study biasReporting biasIndirectnessImprecisionHeterogeneityIncoherenceConfidence
Exenatide extended release and dapagliflozin injection versus Dapagliflozinpendingsomependingsomenonesomepending
Exenatide extended release and dapagliflozin injection versus Dulaglutide injectionpendingsomependingsomenonesomepending
Dapagliflozin versus Dulaglutide injectionpendingsomependingmajornonesomepending
Exenatide extended release and dapagliflozin injection versus Empagliflozinpendingsomependingmajornonesomepending
Dapagliflozin versus Empagliflozinpendingsomependingmajornonesomepending
Dulaglutide injection versus Empagliflozinpendingsomependingsomenonesomepending
Exenatide extended release and dapagliflozin injection versus Exenatide injectionpendingsomependingsomenonesomepending
Dapagliflozin versus Exenatide injectionpendingsomependingmajornonesomepending
Dulaglutide injection versus Exenatide injectionpendingsomependingsomenonesomepending
Empagliflozin versus Exenatide injectionpendingsomependingmajornonesomepending
Exenatide extended release and dapagliflozin injection versus Exenatide extended release injectionpendingsomependingsomenonesomepending
Dapagliflozin versus Exenatide extended release injectionpendingsomependingsomenonesomepending
Dulaglutide injection versus Exenatide extended release injectionpendingsomependingmajornonesomepending
Empagliflozin versus Exenatide extended release injectionpendingsomependingmajornonesomepending
Exenatide injection versus Exenatide extended release injectionpendingsomependingsomenonesomepending
Exenatide extended release and dapagliflozin injection versus Insulin glargine with lixisenatide injectionpendingsomependingsomenonesomepending
Dapagliflozin versus Insulin glargine with lixisenatide injectionpendingsomependingsomenonesomepending
Dulaglutide injection versus Insulin glargine with lixisenatide injectionpendingsomependingsomenonesomepending
Empagliflozin versus Insulin glargine with lixisenatide injectionpendingsomependingsomenonesomepending
Exenatide injection versus Insulin glargine with lixisenatide injectionpendingsomependingsomenonesomepending
Exenatide extended release injection versus Insulin glargine with lixisenatide injectionpendingsomependingsomenonesomepending
Exenatide extended release and dapagliflozin injection versus Insulin glarginependingsomependingsomenonesomepending
Dapagliflozin versus Insulin glarginependingsomependingsomenonesomepending
Dulaglutide injection versus Insulin glarginependingsomependingsomenonesomepending
Empagliflozin versus Insulin glarginependingsomependingsomenonesomepending
Exenatide injection versus Insulin glarginependingsomependingsomenonesomepending
Exenatide extended release injection versus Insulin glarginependingsomependingsomenonesomepending
Insulin glargine with lixisenatide injection versus Insulin glarginependingsomependingsomenonesomepending
Exenatide extended release and dapagliflozin injection versus Liraglutide injectionpendingsomependingsomenonesomepending
Dapagliflozin versus Liraglutide injectionpendingsomependingmajornonesomepending
Dulaglutide injection versus Liraglutide injectionpendingsomependingnonesomesomepending
Empagliflozin versus Liraglutide injectionpendingsomependingsomesomesomepending
Exenatide injection versus Liraglutide injectionpendingsomependingsomesomesomepending
Exenatide extended release injection versus Liraglutide injectionpendingsomependingmajornonesomepending
Insulin glargine with lixisenatide injection versus Liraglutide injectionpendingsomependingsomenonesomepending
Insulin glargine versus Liraglutide injectionpendingsomependingsomenonesomepending
Exenatide extended release and dapagliflozin injection versus Lixisenatide injectionpendingsomependingsomenonesomepending
Dapagliflozin versus Lixisenatide injectionpendingsomependingmajornonesomepending
Dulaglutide injection versus Lixisenatide injectionpendingsomependingnonemajorsomepending
Empagliflozin versus Lixisenatide injectionpendingsomependingsomenonesomepending
Exenatide injection versus Lixisenatide injectionpendingsomependingsomenonesomepending
Exenatide extended release injection versus Lixisenatide injectionpendingsomependingmajornonesomepending
Insulin glargine with lixisenatide injection versus Lixisenatide injectionpendingsomependingsomenonesomepending
Insulin glargine versus Lixisenatide injectionpendingsomependingsomenonesomepending
Liraglutide injection versus Lixisenatide injectionpendingsomependingnonesomesomepending
Exenatide extended release and dapagliflozin injection versus Semaglutide tabletpendingsomependingmajornonesomepending
Dapagliflozin versus Semaglutide tabletpendingsomependingmajornonesomepending
Dulaglutide injection versus Semaglutide tabletpendingsomependingsomenonesomepending
Empagliflozin versus Semaglutide tabletpendingsomependingsomesomesomepending
Exenatide injection versus Semaglutide tabletpendingsomependingsomenonesomepending
Exenatide extended release injection versus Semaglutide tabletpendingsomependingsomenonesomepending
Insulin glargine with lixisenatide injection versus Semaglutide tabletpendingsomependingsomenonesomepending
Insulin glargine versus Semaglutide tabletpendingsomependingnonesomesomepending
Liraglutide injection versus Semaglutide tabletpendingsomependingsomenonesomepending
Lixisenatide injection versus Semaglutide tabletpendingsomependingsomenonesomepending
Exenatide extended release and dapagliflozin injection versus Semaglutide injectionpendingsomependingmajornonesomepending
Dapagliflozin versus Semaglutide injectionpendingsomependingsomesomesomepending
Dulaglutide injection versus Semaglutide injectionpendingsomependingsomenonesomepending
Empagliflozin versus Semaglutide injectionpendingsomependingsomenonesomepending
Exenatide injection versus Semaglutide injectionpendingsomependingsomenonesomepending
Exenatide extended release injection versus Semaglutide injectionpendingsomependingsomenonesomepending
Insulin glargine with lixisenatide injection versus Semaglutide injectionpendingsomependingsomenonesomepending
Insulin glargine versus Semaglutide injectionpendingsomependingnonenonesomepending
Liraglutide injection versus Semaglutide injectionpendingsomependingsomenonesomepending
Lixisenatide injection versus Semaglutide injectionpendingsomependingsomenonesomepending
Semaglutide tablet versus Semaglutide injectionpendingsomependingsomenonesomepending
Exenatide extended release and dapagliflozin injection versus Sitagliptinpendingsomependingsomenonesomepending
Dapagliflozin versus Sitagliptinpendingsomependingsomenonesomepending
Dulaglutide injection versus Sitagliptinpendingsomependingnonesomesomepending
Empagliflozin versus Sitagliptinpendingsomependingsomenonesomepending
Exenatide injection versus Sitagliptinpendingsomependingsomenonesomepending
Exenatide extended release injection versus Sitagliptinpendingsomependingsomesomesomepending
Insulin glargine with lixisenatide injection versus Sitagliptinpendingsomependingsomenonesomepending
Insulin glargine versus Sitagliptinpendingsomependingsomenonesomepending
Liraglutide injection versus Sitagliptinpendingsomependingsomenonesomepending
Lixisenatide injection versus Sitagliptinpendingsomependingsomenonesomepending
Semaglutide tablet versus Sitagliptinpendingsomependingsomenonesomepending
Semaglutide injection versus Sitagliptinpendingsomependingsomenonesomepending
Exenatide extended release and dapagliflozin injection versus Tirzepatide injectionpendingsomependingsomenonesomepending
Dapagliflozin versus Tirzepatide injectionpendingsomependingsomenonesomepending
Dulaglutide injection versus Tirzepatide injectionpendingsomependingnonenonesomepending
Empagliflozin versus Tirzepatide injectionpendingsomependingsomenonesomepending
Exenatide injection versus Tirzepatide injectionpendingsomependingsomenonesomepending
Exenatide extended release injection versus Tirzepatide injectionpendingsomependingsomenonesomepending
Insulin glargine with lixisenatide injection versus Tirzepatide injectionpendingsomependingnonenonesomepending
Insulin glargine versus Tirzepatide injectionpendingsomependingnonenonesomepending
Liraglutide injection versus Tirzepatide injectionpendingsomependingnonesomesomepending
Lixisenatide injection versus Tirzepatide injectionpendingsomependingnonenonesomepending
Semaglutide tablet versus Tirzepatide injectionpendingsomependingsomenonesomepending
Semaglutide injection versus Tirzepatide injectionpendingsomependingsomenonesomepending
Sitagliptin versus Tirzepatide injectionpendingsomependingnonenonesomepending

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.

Rank probabilities

Probability of each rank for each treatment
TreatmentRank 1Rank 2Rank 3Rank 4Rank 5Rank 6Rank 7Rank 8Rank 9Rank 10Rank 11Rank 12Rank 13Rank 14Rank 15Mean rank
TIRZ_SC93%6%1%1.1
SEMA_SC42%28%16%8%4%2%1%3.2
DAPAEXEN_SC6%38%19%10%9%5%4%3%2%1%1%1%3.6
SEMA_PO4%21%29%21%13%8%3%1%4.6
EMPAGLIFLOZIN6%11%15%16%13%11%10%7%5%3%1%1%6.0
EXEN_SC1%4%9%14%20%19%15%9%5%3%1%6.7
DAPAGLIFLOZIN3%13%12%10%12%9%9%7%7%6%4%3%3%2%7.0
LIRA_SC1%3%10%15%18%19%20%10%4%1%7.6
EXENER_SC1%4%7%8%12%13%12%11%11%8%6%4%2%9.0
LIXI_SC1%2%4%7%10%13%17%20%20%5%1%9.0
DULA_SC1%3%6%12%19%28%26%6%1%9.6
SITAGLIPTIN1%2%4%8%15%39%21%9%2%11.9
PLACEBO1%2%5%19%44%26%3%12.9
IGLARLIXI_SC1%2%3%6%14%19%45%9%13.1
INS_GLARGINE1%1%3%12%83%14.7

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 columnPLACEBOTIRZ_SCSEMA_SCDAPAEXEN_SCSEMA_POEMPAGLIFLOZINDAPAGLIFLOZINEXEN_SCLIRA_SCEXENER_SCLIXI_SCDULA_SCSITAGLIPTINIGLARLIXI_SCINS_GLARGINE
PLACEBOPLACEBO5.95
4.37 to 7.44
3.39
2.14 to 4.62
3.34
0.34 to 6.33
2.68
1.61 to 3.80
2.27
0.23 to 4.38
2.01
-0.90 to 5.05
1.99
0.35 to 3.56
1.69
0.71 to 2.67
1.40
-1.03 to 3.77
1.27
0.03 to 2.49
1.12
0.31 to 1.95
0.37
-0.74 to 1.48
-0.21
-1.80 to 1.43
-1.12
-2.42 to 0.22
TIRZ_SC-5.95
-7.44 to -4.37
TIRZ_SC-2.57
-4.00 to -1.08
-2.61
-5.91 to 0.86
-3.27
-4.92 to -1.48
-3.67
-6.03 to -1.15
-3.95
-7.21 to -0.44
-3.97
-6.13 to -1.74
-4.28
-5.94 to -2.44
-4.56
-7.35 to -1.69
-4.70
-6.49 to -2.77
-4.84
-6.36 to -3.19
-5.58
-7.23 to -3.82
-6.17
-8.24 to -3.94
-7.09
-8.95 to -5.13
SEMA_SC-3.39
-4.62 to -2.14
2.57
1.08 to 4.00
SEMA_SC-0.05
-3.37 to 3.21
-0.70
-2.12 to 0.77
-1.11
-3.33 to 1.22
-1.36
-4.52 to 1.90
-1.42
-3.45 to 0.63
-1.71
-3.14 to -0.25
-2.00
-4.72 to 0.65
-2.12
-3.71 to -0.49
-2.27
-3.60 to -0.88
-3.02
-4.33 to -1.66
-3.60
-5.47 to -1.63
-4.52
-6.20 to -2.78
DAPAEXEN_SC-3.34
-6.33 to -0.34
2.61
-0.86 to 5.91
0.05
-3.21 to 3.37
DAPAEXEN_SC-0.67
-3.75 to 2.53
-1.08
-4.54 to 2.52
-1.32
-3.10 to 0.47
-1.36
-3.91 to 1.22
-1.67
-4.71 to 1.47
-1.96
-3.76 to -0.17
-2.08
-5.23 to 1.27
-2.23
-5.15 to 0.80
-2.99
-6.13 to 0.27
-3.56
-6.87 to -0.13
-4.49
-7.70 to -1.20
SEMA_PO-2.68
-3.80 to -1.61
3.27
1.48 to 4.92
0.70
-0.77 to 2.12
0.67
-2.53 to 3.75
SEMA_PO-0.41
-2.10 to 1.32
-0.68
-3.79 to 2.42
-0.70
-2.57 to 1.13
-1.00
-2.17 to 0.13
-1.29
-3.92 to 1.22
-1.41
-2.84 to -0.01
-1.58
-2.66 to -0.47
-2.31
-3.32 to -1.39
-2.89
-4.67 to -1.16
-3.82
-5.34 to -2.30
EMPAGLIFLOZIN-2.27
-4.38 to -0.23
3.67
1.15 to 6.03
1.11
-1.22 to 3.33
1.08
-2.52 to 4.54
0.41
-1.32 to 2.10
EMPAGLIFLOZIN-0.27
-3.80 to 3.25
-0.28
-2.91 to 2.14
-0.59
-2.68 to 1.42
-0.86
-4.04 to 2.11
-1.01
-3.21 to 1.23
-1.17
-3.18 to 0.91
-1.91
-3.90 to 0.01
-2.48
-4.98 to -0.07
-3.42
-5.69 to -1.15
DAPAGLIFLOZIN-2.01
-5.05 to 0.90
3.95
0.44 to 7.21
1.36
-1.90 to 4.52
1.32
-0.47 to 3.10
0.68
-2.42 to 3.79
0.27
-3.25 to 3.80
DAPAGLIFLOZIN-0.02
-2.53 to 2.51
-0.35
-3.49 to 2.75
-0.62
-2.44 to 1.17
-0.74
-3.98 to 2.48
-0.89
-3.84 to 2.04
-1.65
-4.82 to 1.50
-2.24
-5.56 to 1.15
-3.16
-6.33 to 0.01
EXEN_SC-1.99
-3.56 to -0.35
3.97
1.74 to 6.13
1.42
-0.63 to 3.45
1.36
-1.22 to 3.91
0.70
-1.13 to 2.57
0.28
-2.14 to 2.91
0.02
-2.51 to 2.53
EXEN_SC-0.30
-2.12 to 1.52
-0.59
-2.46 to 1.22
-0.72
-2.63 to 1.32
-0.87
-2.40 to 0.75
-1.60
-3.48 to 0.27
-2.20
-4.36 to 0.00
-3.11
-5.01 to -1.19
LIRA_SC-1.69
-2.67 to -0.71
4.28
2.44 to 5.94
1.71
0.25 to 3.14
1.67
-1.47 to 4.71
1.00
-0.13 to 2.17
0.59
-1.42 to 2.68
0.35
-2.75 to 3.49
0.30
-1.52 to 2.12
LIRA_SC-0.28
-2.89 to 2.17
-0.42
-1.84 to 1.06
-0.57
-1.59 to 0.48
-1.32
-2.46 to -0.20
-1.90
-3.65 to -0.17
-2.82
-4.30 to -1.32
EXENER_SC-1.40
-3.77 to 1.03
4.56
1.69 to 7.35
2.00
-0.65 to 4.72
1.96
0.17 to 3.76
1.29
-1.22 to 3.92
0.86
-2.11 to 4.04
0.62
-1.17 to 2.44
0.59
-1.22 to 2.46
0.28
-2.17 to 2.89
EXENER_SC-0.13
-2.77 to 2.61
-0.29
-2.62 to 2.23
-1.02
-3.60 to 1.63
-1.62
-4.44 to 1.28
-2.54
-5.14 to 0.12
LIXI_SC-1.27
-2.49 to -0.03
4.70
2.77 to 6.49
2.12
0.49 to 3.71
2.08
-1.27 to 5.23
1.41
0.01 to 2.84
1.01
-1.23 to 3.21
0.74
-2.48 to 3.98
0.72
-1.32 to 2.63
0.42
-1.06 to 1.84
0.13
-2.61 to 2.77
LIXI_SC-0.15
-1.50 to 1.19
-0.89
-2.21 to 0.34
-1.49
-2.95 to -0.05
-2.39
-3.96 to -0.93
DULA_SC-1.12
-1.95 to -0.31
4.84
3.19 to 6.36
2.27
0.88 to 3.60
2.23
-0.80 to 5.15
1.58
0.47 to 2.66
1.17
-0.91 to 3.18
0.89
-2.04 to 3.84
0.87
-0.75 to 2.40
0.57
-0.48 to 1.59
0.29
-2.23 to 2.62
0.15
-1.19 to 1.50
DULA_SC-0.74
-1.93 to 0.39
-1.32
-2.94 to 0.27
-2.25
-3.38 to -1.12
SITAGLIPTIN-0.37
-1.48 to 0.74
5.58
3.82 to 7.23
3.02
1.66 to 4.33
2.99
-0.27 to 6.13
2.31
1.39 to 3.32
1.91
-0.01 to 3.90
1.65
-1.50 to 4.82
1.60
-0.27 to 3.48
1.32
0.20 to 2.46
1.02
-1.63 to 3.60
0.89
-0.34 to 2.21
0.74
-0.39 to 1.93
SITAGLIPTIN-0.58
-2.33 to 1.20
-1.50
-2.98 to 0.07
IGLARLIXI_SC0.21
-1.43 to 1.80
6.17
3.94 to 8.24
3.60
1.63 to 5.47
3.56
0.13 to 6.87
2.89
1.16 to 4.67
2.48
0.07 to 4.98
2.24
-1.15 to 5.56
2.20
-0.00 to 4.36
1.90
0.17 to 3.65
1.62
-1.28 to 4.44
1.49
0.05 to 2.95
1.32
-0.27 to 2.94
0.58
-1.20 to 2.33
IGLARLIXI_SC-0.91
-2.49 to 0.59
INS_GLARGINE1.12
-0.22 to 2.42
7.09
5.13 to 8.95
4.52
2.78 to 6.20
4.49
1.20 to 7.70
3.82
2.30 to 5.34
3.42
1.15 to 5.69
3.16
-0.01 to 6.33
3.11
1.19 to 5.01
2.82
1.32 to 4.30
2.54
-0.12 to 5.14
2.39
0.93 to 3.96
2.25
1.12 to 3.38
1.50
-0.07 to 2.98
0.91
-0.59 to 2.49
INS_GLARGINE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.766 (95% CrI 0.460 to 1.300)
Residual deviance
47.3 for 47 data points
DIC
91.8 (pD 44.5)
Largest R-hat
1.005
Smallest ESS
bulk 2,117, tail 2,841
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
0.701
I squared
82%
Q (total)
70.28 on 13 df, P = 0.000
Q (between designs)
52.22, P = 0.000

Inconsistency

Do trials comparing two treatments directly agree with the indirect evidence through other treatments?
Frequentist node splitting (Back-calculation). A small P value means direct and indirect evidence disagree.
ComparisonTrialsDirectIndirectNetworkP
Dulaglutide injection versus Exenatide injection
DULA_SC:EXEN_SC
10.55
-0.96 to 2.06
2.78
-0.70 to 6.26
0.90
-0.48 to 2.29
0.249
Dulaglutide injection versus Insulin glargine
DULA_SC:INS_GLARGINE
2-2.04
-3.06 to -1.01
-3.60
-6.14 to -1.07
-2.26
-3.21 to -1.31
0.261
Dulaglutide injection versus Liraglutide injection
DULA_SC:LIRA_SC
10.71
-0.79 to 2.21
0.50
-0.63 to 1.63
0.58
-0.33 to 1.48
0.828
Dulaglutide injection versus Placebo
DULA_SC:PLACEBO
4-1.20
-2.06 to -0.33
-0.96
-2.22 to 0.29
-1.12
-1.84 to -0.41
0.765
Dulaglutide injection versus Semaglutide tablet
DULA_SC:SEMA_PO
11.48
-0.03 to 3.00
1.65
0.44 to 2.86
1.58
0.64 to 2.53
0.867
Dulaglutide injection versus Tirzepatide injection
DULA_SC:TIRZ_SC
13.43
1.16 to 5.71
5.79
3.98 to 7.61
4.87
3.46 to 6.29
0.111
Exenatide injection versus Placebo
EXEN_SC:PLACEBO
1-2.51
-4.14 to -0.88
-0.61
-3.40 to 2.19
-2.03
-3.44 to -0.61
0.249
Insulin glargine with lixisenatide injection versus Insulin glargine
IGLARLIXI_SC:INS_GLARGINE
1-1.45
-3.03 to 0.13
0.12
-2.11 to 2.34
-0.92
-2.21 to 0.37
0.261
Insulin glargine with lixisenatide injection versus Lixisenatide injection
IGLARLIXI_SC:LIXI_SC
11.94
0.48 to 3.40
0.37
-1.94 to 2.68
1.49
0.26 to 2.73
0.261
Liraglutide injection versus Placebo
LIRA_SC:PLACEBO
2-1.73
-2.83 to -0.63
-1.65
-2.98 to -0.32
-1.70
-2.55 to -0.85
0.928
Liraglutide injection versus Semaglutide tablet
LIRA_SC:SEMA_PO
11.40
-0.12 to 2.92
0.73
-0.53 to 2.00
1.01
0.03 to 1.98
0.510
Liraglutide injection versus Sitagliptin
LIRA_SC:SITAGLIPTIN
1-1.67
-3.20 to -0.14
-1.07
-2.31 to 0.18
-1.31
-2.27 to -0.34
0.548
Lixisenatide injection versus Placebo
LIXI_SC:PLACEBO
1-0.40
-1.91 to 1.11
-2.21
-3.77 to -0.66
-1.28
-2.36 to -0.20
0.101
Lixisenatide injection versus Sitagliptin
LIXI_SC:SITAGLIPTIN
1-1.34
-2.94 to 0.26
-0.42
-2.04 to 1.20
-0.89
-2.03 to 0.26
0.429
Semaglutide tablet versus Placebo
SEMA_PO:PLACEBO
1-4.00
-5.55 to -2.45
-1.97
-3.14 to -0.80
-2.71
-3.64 to -1.77
0.040
Semaglutide injection versus Placebo
SEMA_SC:PLACEBO
1-3.81
-5.44 to -2.18
-3.08
-4.54 to -1.61
-3.40
-4.49 to -2.31
0.512
Tirzepatide injection versus Placebo
TIRZ_SC:PLACEBO
1-5.73
-8.04 to -3.42
-6.14
-7.84 to -4.44
-6.00
-7.37 to -4.63
0.780
Semaglutide tablet versus Sitagliptin
SEMA_PO:SITAGLIPTIN
2-1.89
-2.89 to -0.88
-3.22
-4.68 to -1.76
-2.31
-3.14 to -1.49
0.141
Semaglutide injection versus Sitagliptin
SEMA_SC:SITAGLIPTIN
1-3.20
-4.65 to -1.75
-2.75
-4.45 to -1.05
-3.01
-4.11 to -1.91
0.690
Semaglutide injection versus Tirzepatide injection
SEMA_SC:TIRZ_SC
13.13
1.65 to 4.62
1.36
-0.89 to 3.61
2.59
1.35 to 3.83
0.198
Heterogeneity within designs (decomp.design)
DesignQdfP
DULA_SC:INS_GLARGINE12.9610.000
PLACEBO:DULA_SC0.0410.839
SEMA_PO:SITAGLIPTIN5.0510.025

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.
0.000.611.21-2.50-1.250.001.252.50Centered effectStandard error
Comparisons ordered as DAPAEXEN_SC, DAPAGLIFLOZIN, DULA_SC, EMPAGLIFLOZIN, EXEN_SC, EXENER_SC, IGLARLIXI_SC, INS_GLARGINE, LIRA_SC, LIXI_SC, SEMA_PO, SEMA_SC, SITAGLIPTIN, TIRZ_SC, PLACEBO; the shaded triangle is where 95% of points would fall without small study effects. Egger type test P = 0.028.

Contribution of direct evidence

Percent contribution of each direct comparison (columns) to each network estimate (rows), from netcontrib.

Contribution of direct comparisons to network estimates
Network estimateDAPAEXEN_SC:DAPAGLIFLOZIN:EXENER_SCDULA_SC:EXEN_SC:PLACEBODULA_SC:INS_GLARGINEDULA_SC:LIRA_SCDULA_SC:PLACEBODULA_SC:PLACEBO:TIRZ_SCDULA_SC:SEMA_POEMPAGLIFLOZIN:SEMA_POEXEN_SC:EXENER_SCIGLARLIXI_SC:INS_GLARGINEIGLARLIXI_SC:LIXI_SCLIRA_SC:PLACEBOLIRA_SC:PLACEBO:SEMA_POLIRA_SC:SITAGLIPTINLIXI_SC:PLACEBOLIXI_SC:SITAGLIPTINPLACEBO:SEMA_SCSEMA_PO:SITAGLIPTINSEMA_SC:SITAGLIPTINSEMA_SC:TIRZ_SC
DAPAEXEN_SC:PLACEBO3228151126111
DAPAGLIFLOZIN:PLACEBO3228151126111
DULA_SC:PLACEBO24273775224722111
EMPAGLIFLOZIN:PLACEBO41619343212333831
EXEN_SC:PLACEBO741311221113111
EXENER_SC:PLACEBO421272239111211
IGLARLIXI_SC:PLACEBO51417211422241185222
INS_GLARGINE:PLACEBO11354164366255111
LIRA_SC:PLACEBO511711253452223
LIXI_SC:PLACEBO243114425352102431
PLACEBO:SEMA_PO51921453734431041
PLACEBO:SEMA_SC239125433455118
PLACEBO:SITAGLIPTIN312425116151289814102
PLACEBO:TIRZ_SC573813222142520

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; 22 of 23
Sex (percent female)
effect modifier, prognostic factor; 23 of 23
Background glucose lowering therapy (stratum S0 to S4)
effect modifier, prognostic factor; 23 of 23
Asian ancestry or region (percent Asian)
effect modifier, prognostic factor; 22 of 23
Kidney function (eGFR) (mL/min/1.73 m2)
prognostic factor, effect modifier; 10 of 23
Treatment duration (weeks)
effect modifier; 23 of 23
Lifestyle co-intervention intensity (none standard intensive)
effect modifier, prognostic factor; 23 of 23
NCT03131687
S000010
32.5746.85S11.6693.1926standard
NCT02964247
S000022
32.239.6S117.48not reported26not_reported
SURPASS-2
S000095
34.253.05S11.329640not_reported
PIONEER 4
S000133
32.9448S113.495.852not_reported
NCT01476475
S000191
32.148.92S10.62not reported24not_reported
PIONEER 10
S000234
26.2625.74S110096.5752not_reported
NCT01584232
S000246
2628.51S1100not reported26not_reported
PIONEER 2
S000251
32.8549.39S15.9695.552not_reported
AWARD-10
S000305
32.6849.99S10.2490.924not_reported
NCT00976937
S000415
36.859.9
100 minus male share
S10.6not reported24not_reported
SUSTAIN 9
S000483
31.941.72S123.5195.230not_reported
PIONEER 12
S000522
28.5841.7S175.22103.526not_reported
NCT02229396
S000791
32.7352S10.72
eGFR below 60: 3.2 percent
104not_reported
AWARD-8
S001068
31.255.86S11.789.7624not_reported
LIRA-SWITCH™
S001119
31.9540.5S1not reportednot reported26not_reported
AWARD-2
S001130
31.5548.52S116.91
eGFR below 60: 1.1 percent
78not_reported
AWARD-6
S001184
33.5652.09S10.17not reported26not_reported
SUSTAIN
S001311
27.842.5S185.03109.33
median
30not_reported
DURATION-NEO-1
S001982
3335.81S16.61
eGFR below 60: 11.8 percent
28none
LIXILAN JP-O1
S002018
26.8235.85S1100
region: all sites in Asia
not reported52not_reported
AWARD-1
S002153
33.1641.51S12.45
eGFR below 60: 2.8 percent
52not_reported
GETGOAL-M
S002188
32.9156.94S17.78not reported24not_reported
PIONEER 3
S002267
not reported47.16S113.14not reported78not_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 26.3 (DULA_SC vs SEMA_PO) to 36.8 (LIXI_SC vs SITAGLIPTIN) kg/m2; threshold 3
  • FlagBaseline, Sex: design means range from 25.7 (DULA_SC vs SEMA_PO) to 59.9 (LIXI_SC vs SITAGLIPTIN) percent female; threshold 15
  • FlagBaseline, Asian ancestry or region: design means range from 0.2 (DULA_SC vs LIRA_SC) to 100.0 (DULA_SC vs SEMA_PO) percent Asian; threshold 30
  • FlagBaseline, Kidney function (eGFR): not reported by 13 of 23 trials
  • FlagBaseline, Kidney function (eGFR): design means range from 90.3 (DULA_SC vs PLACEBO) to 109.3 (SEMA_SC vs SITAGLIPTIN) mL/min/1.73 m2; threshold 15
  • FlagBaseline, Treatment duration: design means range from 24.0 (DULA_SC vs PLACEBO) to 104.0 (DAPAEXEN_SC vs DAPAGLIFLOZIN vs EXENER_SC) weeks; threshold 26
  • NoteOutcome assessment, time point: selected time points span 24 to 30 weeks
  • NoteOutcome assessment, analysis set: mixed: full_analysis 10, modified_itt 13
  • NoteOutcome assessment, definition: mixed: change in HbA1c from baseline 1, change in HbA1c from baseline to week 26, LOCF 1, not stated 21
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 13, not stated 9, treatment_policy 1
  • NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 20, not stated 3
  • NoteRisk of bias, blinding: mixed: double_blind 14, open_label 6, single_blind 3
  • NoteData handling, input conversions: arms_combined 10, n_randomized 2
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
NCT0313168726modified_ittnot statednot statednot statednot statedtreatment_policyhypotheticaldouble_blindindustry2017age 18 to 75; T2D at least 6 months; HbA1c 7.0 to 10.5%; BMI 23 to 50; diet and exercise or metformin
NCT0296424726full_analysisnot statednot statednot statednot statednot statednot stateddouble_blindindustry2017age 18 or more; HbA1c 7.0 to 9.5%; BMI 20 or more; stable SGLT2i at least 90 days with or without metformin; eGFR 60 or more
SURPASS-224modified_ittnot statednot statednot statednot statedhypotheticalhypotheticalsingle_blindindustry2019age 18 or older, HbA1c 7.0 to 10.5 percent, BMI 25 or more, metformin 1500 mg/day or more, eGFR 45 or more
PIONEER 426full_analysisnot statednot statednot statednot statedhypotheticalhypotheticaldouble_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_analysisnot statednot 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
PIONEER 226full_analysisnot statednot statednot statednot statedhypotheticalhypotheticalsingle_blindindustry2016type 2 diabetes on metformin; HbA1c 7.0 to 10.5 percent; eGFR 60 or more
AWARD-1024modified_ittnot statednot statednot statednot statednot statedhypotheticaldouble_blindindustry2015T2D; HbA1c 7.0 to 9.5 percent; BMI 45 or lower; SGLT2i with or without metformin
NCT0097693724modified_ittnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2009age 18 to under 50; BMI 30 or more; HbA1c 7.0 to 10 percent; metformin at least 1.5 g/day
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
NCT0222939628modified_ittnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2014age 18 or older; HbA1c 8.0 to 12.0 percent on metformin 1500 mg/d or more
AWARD-824modified_ittnot statednot statednot statednot statednot statedhypotheticaldouble_blindindustry2013age 18 or older; BMI up to 45; HbA1c 7.5 to 9.5 percent on sulfonylurea at least half maximal dose
LIRA-SWITCH™26full_analysisnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2013age 18 or more; HbA1c 7.5 to 9.5 percent; BMI 20 or more; on sitagliptin 100 mg and metformin for 90 days or more
AWARD-226modified_ittnot statednot statednot statednot statednot statedhypotheticalopen_labelindustry2010type 2 diabetes on metformin and glimepiride
AWARD-626modified_ittchange in HbA1c from baselinenot statednot statednot statednot statednot statedopen_labelindustry2012adults; HbA1c 7 to 10 percent; metformin 1500 mg/day or more
SUSTAIN30full_analysisnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2017Adults 18 or older, HbA1c 7.0 to 10.5 percent on metformin monotherapy, eGFR 60 or more
DURATION-NEO-128modified_ittnot statednot statednot statednot statednot statedhypotheticalopen_labelindustry2013Adults 18 or older; HbA1c 7.1 to 11.0 percent; diet and exercise or stable metformin, sulfonylurea, pioglitazone
LIXILAN JP-O126modified_ittchange in HbA1c from baseline to week 26, LOCFnot statednot statednot statedhypotheticalhypotheticalopen_labelindustry2016insulin naive Japanese adults; HbA1c 7.5 to 10%; FPG 13.8 mmol/L or less; one or two OADs
AWARD-126modified_ittnot statednot statednot statednot statednot statedhypotheticaldouble_blindindustry2010adults with type 2 diabetes on metformin and pioglitazone
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
PIONEER 326full_analysisnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2016adults with T2D; HbA1c 7.0 to 10.5 percent; metformin with or without sulfonylurea

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
NCT03131687A1PLACEBO26arm, change-0.4000.81041R0016215:Supplement Table 1
NCT03131687A2+A3+A4+A5TIRZ_SC26arm, change-6.1300.498171arms_combinedR0016215:Supplement Table 1
NCT03131687A6DULA_SC26arm, change-2.7000.78047R0016215:Supplement Table 1
NCT02964247A1LIRA_SC26arm, change-2.8900.267203registry:outcomes
NCT02964247A2PLACEBO26arm, change-2.0900.296100registry:outcomes
SURPASS-2A1+A2+A3TIRZ_SC24arm, change-8.4320.1481,410n_randomized;arms_combinedR0007660:Table 1
SURPASS-2A4SEMA_SC24arm, change-5.3000.250469n_randomizedR0007660:Table 1
PIONEER 4A1SEMA_PO26arm, change-4.7000.255285registry:outcomes
PIONEER 4A2LIRA_SC26arm, change-3.3000.220284registry:outcomes
PIONEER 4A3PLACEBO26arm, change-0.7000.260142registry:outcomes
NCT01476475A1IGLARLIXI_SC24arm, change-0.9700.289159registry:outcomes
NCT01476475A2INS_GLARGINE24arm, change0.4800.282160registry:outcomes
PIONEER 10A1+A2+A3SEMA_PO26arm, change-1.1820.124370arms_combinedR0018421:Figure 3D
PIONEER 10A4DULA_SC26arm, change0.3000.30064R0018421:Figure 3D
NCT01584232A1DULA_SC26arm, change-0.4800.170180R0016159:Table 2
NCT01584232A2INS_GLARGINE26arm, change0.9400.170180R0016159:Table 2
PIONEER 2A1SEMA_PO26arm, change-4.3000.217411registry:outcomes
PIONEER 2A2EMPAGLIFLOZIN26arm, change-3.9000.188410registry:outcomes
AWARD-10A1+A2DULA_SC24arm, change-2.8510.212283arms_combinedregistry:outcomes
AWARD-10A3PLACEBO24arm, change-2.3000.310140registry:outcomes
NCT00976937A1LIXI_SC24arm, change-2.5100.294152registry:outcomes
NCT00976937A2SITAGLIPTIN24arm, change-1.1700.304160registry:outcomes
SUSTAIN 9A1SEMA_SC30contrast, md-3.8100.452R0021710:Figure 3b
SUSTAIN 9A2PLACEBO30contrast, mdR0021710:Figure 3b
PIONEER 12A1+A2+A3SEMA_PO26arm, change-2.6740.113941arms_combinedregistry:outcomes
PIONEER 12A4SITAGLIPTIN26arm, change-0.5000.142335registry:outcomes
NCT02229396A1DAPAEXEN_SC28arm, change-3.5500.288228R0026313:Table 3
NCT02229396A2EXENER_SC28arm, change-1.5600.293227R0026313:Table 3
NCT02229396A3DAPAGLIFLOZIN28arm, change-2.2200.286230R0026313:Table 3
AWARD-8A1DULA_SC24arm, change-0.9100.210212R0016038:Results
AWARD-8A2PLACEBO24arm, change-0.2400.40053R0016038:Results
LIRA-SWITCH™A1LIRA_SC26contrast, md-1.6700.344R0025720:Results
LIRA-SWITCH™A2SITAGLIPTIN26contrast, mdR0025720:Results
AWARD-2A1+A2DULA_SC26arm, change-1.6460.141542arms_combinedregistry:outcomes
AWARD-2A3INS_GLARGINE26arm, change1.0100.200259registry:outcomes
AWARD-6A1DULA_SC26arm, change-2.9000.220299registry:outcomes
AWARD-6A2LIRA_SC26arm, change-3.6100.220299registry:outcomes
SUSTAINA1+A2SEMA_SC30arm, change-3.6010.174477arms_combinedregistry:outcomes
SUSTAINA3SITAGLIPTIN30arm, change-0.4000.157253registry:outcomes
DURATION-NEO-1A1EXENER_SC28contrast, md0.5500.416R0022632:Results
DURATION-NEO-1A2EXEN_SC28contrast, mdR0022632:Results
LIXILAN JP-O1A1IGLARLIXI_SC26arm, change0.6200.177161R0015751:Table 2
LIXILAN JP-O1A2LIXI_SC26arm, change-1.3200.180157R0015751:Table 2
AWARD-1A1+A2DULA_SC26arm, change-0.5890.180512arms_combinedregistry:outcomes
AWARD-1A3EXEN_SC26arm, change-1.1400.260245registry:outcomes
AWARD-1A4PLACEBO26arm, change1.3700.370109registry:outcomes
GETGOAL-MA1+A2LIXI_SC24arm, change-2.0000.166497arms_combinedR0025872:Results
GETGOAL-MA3PLACEBO24arm, change-1.6000.270168R0025872:Results
PIONEER 3A1+A2+A3SEMA_PO26arm, change-2.1990.1021,396arms_combinedregistry:outcomes
PIONEER 3A4SITAGLIPTIN26arm, change-0.6000.148467registry:outcomes

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