LivingGLP1
Network meta-analysis

Discontinuation due to gastrointestinal adverse events

Type 2 diabetes (adults)

longest follow-upRecorded harmsDoses of a drug pooledHazard ratio (from event counts)
50
Randomized trials
30
Treatments
21,588
Participants
678
Events

In plain language

Across 50 trials with 21,588 participants, 4 of 29 treatments had a clearly better result than placebo on discontinuation due to gastrointestinal adverse events, 5 a clearly worse one, and for 20 the evidence could not tell them apart from placebo. The most favorable estimate was for insulin glargine: hazard ratio (from event counts) 0.02 (95% credible interval 0.00 to 0.15).

  • Insulin glargine: better than placebo but not among the most effective (certainty pending).
  • Insulin aspart (prandial): better than placebo but not among the most effective (certainty pending).
  • Premixed insulin: not convincingly different from placebo (certainty pending).
  • Sulfonylurea: better than placebo but not among the most effective (certainty pending).
  • Additional oad: not convincingly different from placebo (certainty pending).
  • Dapagliflozin: not convincingly different from placebo (certainty pending).
  • Standard care or no added treatment: not convincingly different from placebo (certainty pending).
  • Sitagliptin: better than placebo but not among the most effective (certainty pending).
  • Polyethylene glycol loxenatide injection: not convincingly different from placebo (certainty pending).
  • Exenatide extended release and dapagliflozin injection: not convincingly different from placebo (certainty pending).
  • Medi41 sc: not convincingly different from placebo (certainty pending).
  • Dulaglutide injection: not convincingly different from placebo (certainty pending).
  • Investigator choice oral drug: not convincingly different from placebo (certainty pending).
  • Liraglutide and metformin injection: not convincingly different from placebo (certainty pending).
  • Metformin: not convincingly different from placebo (certainty pending).
  • Linagliptin: not convincingly different from placebo (certainty pending).
  • Insulin glargine with lixisenatide injection: not convincingly different from placebo (certainty pending).
  • Exenatide extended release injection: not convincingly different from placebo (certainty pending).
  • Taspoglutide injection: not convincingly different from placebo (certainty pending).
  • Tirzepatide injection: not convincingly different from placebo (certainty pending).
  • Semaglutide injection: worse than placebo (certainty pending).
  • Liraglutide injection: worse than placebo (certainty pending).
  • Efpeglenatide injection: not convincingly different from placebo (certainty pending).
  • Semaglutide tablet: worse than placebo (certainty pending).
  • Insulin icodec with semaglutide injection: not convincingly different from placebo (certainty pending).
  • Lixisenatide injection: worse than placebo (certainty pending).
  • Safiglipron (HRS-7535) tablet: not convincingly different from placebo (certainty pending).
  • Exenatide injection: worse than placebo (certainty pending).
  • Danuglipron tablet: 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.
DANU_PODAPAEXEN_SCDAPAGLIFLOZINDULA_SCEFPE_SCEXENER_SCEXEN_SCICOSEMA_SCIGLARLIXI_SCINS_ASPARTINS_GLARGINEINS_PREMIXLINAGLIPTINLIRAMETF_SCLIRA_SCLIXI_SCMEDI41_SCMETFORMINOTHER_ACTIVE_additional_OADOTHER_ACTIVE_investigator_choice_oral_drugOTHER_ACTIVE_sulfonylureaPEGLOX_SCPLACEBOSAFIGL_POSEMA_POSEMA_SCSITAGLIPTINSTANDARD_CARETASP_SCTIRZ_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

Hazard ratio (from event counts). Lower values favor the treatment.
0.010.020.050.10.20.250.51245102050100← favors treatmentfavors reference →Insulin glargineInsulin aspart (prandial)Premixed insulinSulfonylureaAdditional oadDapagliflozinStandard care or no added treatm…SitagliptinPolyethylene glycol loxenatide i…Exenatide extended release and d…Medi41 scDulaglutide injectionInvestigator choice oral drugLiraglutide and metformin inject…MetforminLinagliptinInsulin glargine with lixisenati…Exenatide extended release injec…Taspoglutide injectionTirzepatide injectionSemaglutide injectionLiraglutide injectionEfpeglenatide injectionSemaglutide tabletInsulin icodec with semaglutide …Lixisenatide injectionSafiglipron (HRS-7535) tabletExenatide injectionDanuglipron tablet
Versus Placebo, log scale. Blue: Bayesian random effects posterior median with 95% credible interval (thick) and 95% prediction interval (dashed). Amber diamond: frequentist estimate with 95% confidence interval. Hover over or tab to a row for its values.
Effects of each treatment versus Placebo
TreatmentBayesian HR (95% CrI)95% prediction intervalFrequentist HR (95% CI)VerdictConfidence
Insulin glargine
INS_GLARGINE
0.02 (0.00 to 0.15)0.00 to 0.16Betterpending
Insulin aspart (prandial)
INS_ASPART
0.06 (0.00 to 0.66)0.00 to 0.75Betterpending
Premixed insulin
INS_PREMIX
0.07 (0.00 to 2.19)0.00 to 2.41Unclearpending
Sulfonylurea
OTHER_ACTIVE_sulfonylurea
0.08 (0.00 to 0.98)0.00 to 1.06Betterpending
Additional oad
OTHER_ACTIVE_additional_OAD
0.11 (0.00 to 1.27)0.00 to 1.43Unclearpending
Dapagliflozin
DAPAGLIFLOZIN
0.14 (0.00 to 3.42)0.00 to 3.90Unclearpending
Standard care or no added treatment
STANDARD_CARE
0.19 (0.00 to 5.67)0.00 to 6.02Unclearpending
Sitagliptin
SITAGLIPTIN
0.21 (0.06 to 0.62)0.05 to 0.72Betterpending
Polyethylene glycol loxenatide injection
PEGLOX_SC
0.38 (0.00 to 29.15)0.00 to 31.95Unclearpending
Exenatide extended release and dapagliflozin injection
DAPAEXEN_SC
0.42 (0.01 to 36.60)0.00 to 39.65Unclearpending
Medi41 sc
MEDI41_SC
0.48 (0.01 to 35.75)0.00 to 38.85Unclearpending
Dulaglutide injection
DULA_SC
0.54 (0.15 to 1.80)0.13 to 2.07Unclearpending
Investigator choice oral drug
OTHER_ACTIVE_investigator_choice_oral_drug
0.58 (0.17 to 1.84)0.15 to 2.21Unclearpending
Liraglutide and metformin injection
LIRAMETF_SC
0.71 (0.01 to 50.68)0.01 to 50.87Unclearpending
Metformin
METFORMIN
0.71 (0.01 to 49.61)0.01 to 51.01Unclearpending
Linagliptin
LINAGLIPTIN
0.73 (0.01 to 55.27)0.01 to 58.11Unclearpending
Insulin glargine with lixisenatide injection
IGLARLIXI_SC
1.41 (0.08 to 28.36)0.08 to 29.56Unclearpending
Exenatide extended release injection
EXENER_SC
1.46 (0.59 to 3.46)0.45 to 4.51Unclearpending
Taspoglutide injection
TASP_SC
2.71 (0.51 to 14.84)0.43 to 17.05Unclearpending
Tirzepatide injection
TIRZ_SC
2.85 (0.74 to 11.45)0.65 to 13.26Unclearpending
Semaglutide injection
SEMA_SC
3.66 (2.08 to 6.79)1.58 to 9.20Worsepending
Liraglutide injection
LIRA_SC
3.67 (1.71 to 8.07)1.33 to 10.08Worsepending
Efpeglenatide injection
EFPE_SC
3.85 (0.99 to 21.06)0.86 to 22.35Unclearpending
Semaglutide tablet
SEMA_PO
3.89 (1.37 to 10.32)1.09 to 11.90Worsepending
Insulin icodec with semaglutide injection
ICOSEMA_SC
4.01 (0.63 to 27.18)0.55 to 30.75Unclearpending
Lixisenatide injection
LIXI_SC
6.37 (1.52 to 35.85)1.29 to 40.84Worsepending
Safiglipron (HRS-7535) tablet
SAFIGL_PO
6.70 (0.75 to 113)0.67 to 122Unclearpending
Exenatide injection
EXEN_SC
6.97 (1.35 to 44.39)1.22 to 50.37Worsepending
Danuglipron tablet
DANU_PO
7.60 (0.74 to 243)0.66 to 255Unclearpending

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
Danuglipron tablet versus Placebopendingnonependingmajornonesomepending
Exenatide extended release and dapagliflozin injection versus Placebopendingnonependingmajornonesomepending
Dapagliflozin versus Placebopendingnonependingmajornonesomepending
Dulaglutide injection versus Placebopendingnonependingmajornonesomepending
Efpeglenatide injection versus Placebopendingnonependingsomenonesomepending
Exenatide injection versus Placebopendingnonependingnonesomesomepending
Exenatide extended release injection versus Placebopendingnonependingmajornonesomepending
Insulin icodec with semaglutide injection versus Placebopendingnonependingmajornonesomepending
Insulin glargine with lixisenatide injection versus Placebopendingnonependingmajornonesomepending
Insulin aspart (prandial) versus Placebopendingnonependingnonenonesomepending
Insulin glargine versus Placebopendingnonependingnonenonesomepending
Premixed insulin versus Placebopendingnonependingmajornonesomepending
Linagliptin versus Placebopendingnonependingmajornonesomepending
Liraglutide injection versus Placebopendingnonependingnonenonesomepending
Liraglutide and metformin injection versus Placebopendingnonependingmajornonesomepending
Lixisenatide injection versus Placebopendingnonependingnonenonesomepending
Medi41 sc versus Placebopendingnonependingmajornonesomepending
Metformin versus Placebopendingnonependingmajornonesomepending
Additional oad versus Placebopendingnonependingmajornonesomepending
Investigator choice oral drug versus Placebopendingnonependingmajornonesomepending
Sulfonylurea versus Placebopendingnonependingsomenonesomepending
Polyethylene glycol loxenatide injection versus Placebopendingnonependingmajornonesomepending
Safiglipron (HRS-7535) tablet versus Placebopendingnonependingmajornonesomepending
Semaglutide tablet versus Placebopendingnonependingnonesomesomepending
Semaglutide injection versus Placebopendingnonependingnonenonesomepending
Sitagliptin versus Placebopendingnonependingnonenonesomepending
Standard care or no added treatment versus Placebopendingnonependingmajornonesomepending
Taspoglutide injection versus Placebopendingnonependingmajornonesomepending
Tirzepatide injection versus Placebopendingnonependingmajornonesomepending

This network has 435 rated comparisons; the table lists those with the reference. All of them are in the API record of this network.

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 15Rank 16Rank 17Rank 18Rank 19Rank 20Rank 21Rank 22Rank 23Rank 24Rank 25Rank 26Rank 27Rank 28Rank 29Rank 30Mean rank
INS_GLARGINE32%24%16%12%7%4%3%1%1%2.8
INS_ASPART10%11%12%12%11%10%8%7%6%4%3%2%1%1%5.4
OTHER_ACTIVE_sulfonylurea10%10%11%11%10%10%8%8%6%5%3%3%2%1%1%1%5.9
INS_PREMIX10%11%12%10%9%8%7%6%5%4%4%3%2%2%1%1%1%1%1%6.4
OTHER_ACTIVE_additional_OAD7%8%9%9%10%9%9%8%7%5%5%5%3%3%1%1%1%1%6.9
DAPAGLIFLOZIN7%7%8%8%8%8%7%7%6%6%5%4%4%3%2%2%2%1%1%1%1%8.1
SITAGLIPTIN1%3%6%10%15%17%16%12%9%5%3%1%1%8.4
STANDARD_CARE6%7%7%7%8%7%6%6%6%6%5%4%4%4%3%2%2%2%2%1%1%1%1%1%1%1%1%9.3
DULA_SC1%1%3%5%8%11%14%14%13%10%7%5%4%2%1%12.1
OTHER_ACTIVE_investigator_choice_oral_drug1%2%4%7%11%14%15%14%12%7%5%3%2%1%1%12.3
PEGLOX_SC4%4%5%5%5%6%6%5%5%5%4%4%4%3%3%3%3%3%2%2%2%1%1%2%2%2%2%2%2%3%12.4
DAPAEXEN_SC3%5%5%5%5%5%5%5%5%5%5%4%4%3%4%3%3%3%2%2%1%1%1%2%2%2%2%2%3%3%12.6
MEDI41_SC3%3%4%5%5%5%5%5%5%5%4%5%4%3%3%3%3%3%2%2%2%2%2%2%2%2%2%2%3%4%13.2
LIRAMETF_SC3%3%4%4%5%4%4%5%4%4%4%4%4%3%4%3%3%3%3%3%2%2%2%2%2%2%3%3%4%5%14.6
METFORMIN3%3%3%4%4%4%5%5%4%4%4%4%4%3%3%3%3%3%3%2%2%2%2%2%2%2%3%3%4%5%14.6
LINAGLIPTIN3%3%4%4%4%4%4%4%4%4%4%4%4%3%3%3%4%3%3%2%2%2%2%2%2%3%2%3%4%5%14.6
PLACEBO1%3%6%13%20%22%18%11%5%1%1%14.8
EXENER_SC1%1%3%5%7%11%15%16%15%11%7%4%2%1%16.9
IGLARLIXI_SC1%1%2%2%3%4%5%5%6%5%5%5%5%5%5%5%4%3%3%3%3%3%3%3%4%4%3%17.3
TASP_SC1%1%2%3%3%4%6%7%8%8%8%6%6%6%6%5%6%5%4%3%1%20.7
TIRZ_SC1%1%2%3%5%7%9%10%9%9%7%7%7%6%6%5%4%2%1%21.1
LIRA_SC1%2%3%6%9%12%13%14%12%11%8%5%2%1%22.7
SEMA_SC1%2%5%9%13%16%16%14%11%6%4%2%22.7
ICOSEMA_SC1%1%2%2%3%3%4%5%6%6%6%6%6%6%7%7%8%8%7%6%22.8
EFPE_SC1%1%2%3%5%5%6%7%7%7%7%8%8%8%8%7%6%4%22.9
SEMA_PO1%1%2%4%6%8%9%11%11%11%10%9%7%5%2%1%23.0
SAFIGL_PO1%1%1%2%2%3%4%4%4%4%4%4%5%5%7%8%10%13%18%24.8
DANU_PO1%1%1%2%2%3%3%3%4%4%3%4%4%5%6%7%9%13%25%25.1
LIXI_SC1%2%2%3%4%5%5%5%6%9%11%14%15%12%5%25.3
EXEN_SC1%1%1%2%3%3%4%4%5%6%7%10%12%14%16%10%25.6

League table

Every treatment against every other: hazard ratio (from event counts) 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 columnPLACEBOINS_GLARGINEINS_ASPARTINS_PREMIXOTHER_ACTIVE_sulfonylureaOTHER_ACTIVE_additional_OADDAPAGLIFLOZINSTANDARD_CARESITAGLIPTINPEGLOX_SCDAPAEXEN_SCMEDI41_SCDULA_SCOTHER_ACTIVE_investigator_choice_oral_drugLIRAMETF_SCMETFORMINLINAGLIPTINIGLARLIXI_SCEXENER_SCTASP_SCTIRZ_SCSEMA_SCLIRA_SCEFPE_SCSEMA_POICOSEMA_SCLIXI_SCSAFIGL_POEXEN_SCDANU_PO
PLACEBOPLACEBO61.92
6.55 to 1382
15.47
1.52 to 519
13.41
0.46 to 594
13.17
1.02 to 530
9.12
0.79 to 363
7.16
0.29 to 403
5.30
0.18 to 318
4.65
1.62 to 16.63
2.62
0.03 to 229
2.39
0.03 to 196
2.10
0.03 to 197
1.85
0.55 to 6.52
1.73
0.54 to 5.94
1.41
0.02 to 158
1.41
0.02 to 144
1.37
0.02 to 154
0.71
0.04 to 12.73
0.68
0.29 to 1.71
0.37
0.07 to 1.97
0.35
0.09 to 1.35
0.27
0.15 to 0.48
0.27
0.12 to 0.59
0.26
0.05 to 1.01
0.26
0.10 to 0.73
0.25
0.04 to 1.59
0.16
0.03 to 0.66
0.15
0.01 to 1.34
0.14
0.02 to 0.74
0.13
0.00 to 1.35
INS_GLARGINE0.02
0.00 to 0.15
INS_GLARGINE0.26
0.01 to 15.86
0.21
0.00 to 14.03
0.21
0.00 to 15.87
0.14
0.00 to 10.30
0.11
0.00 to 11.42
0.08
0.00 to 9.17
0.08
0.00 to 1.01
0.04
0.00 to 5.98
0.03
0.00 to 6.17
0.03
0.00 to 5.02
0.03
0.00 to 0.26
0.03
0.00 to 0.34
0.02
0.00 to 4.34
0.02
0.00 to 3.99
0.02
0.00 to 4.13
0.01
0.00 to 0.25
0.01
0.00 to 0.12
0.01
0.00 to 0.11
0.01
0.00 to 0.06
0.00
0.00 to 0.04
0.00
0.00 to 0.04
0.00
0.00 to 0.06
0.00
0.00 to 0.05
0.00
0.00 to 0.07
0.00
0.00 to 0.04
0.00
0.00 to 0.06
0.00
0.00 to 0.04
0.00
0.00 to 0.06
INS_ASPART0.06
0.00 to 0.66
3.90
0.06 to 187
INS_ASPART0.79
0.01 to 73.68
0.85
0.01 to 66.81
0.57
0.01 to 45.90
0.44
0.00 to 44.87
0.33
0.00 to 36.40
0.30
0.01 to 4.13
0.14
0.00 to 27.05
0.14
0.00 to 26.47
0.12
0.00 to 20.07
0.12
0.00 to 1.80
0.11
0.00 to 1.53
0.08
0.00 to 16.89
0.08
0.00 to 16.64
0.08
0.00 to 15.54
0.04
0.00 to 2.00
0.04
0.00 to 0.53
0.02
0.00 to 0.42
0.02
0.00 to 0.34
0.02
0.00 to 0.18
0.02
0.00 to 0.20
0.02
0.00 to 0.26
0.02
0.00 to 0.22
0.02
0.00 to 0.32
0.01
0.00 to 0.17
0.01
0.00 to 0.24
0.01
0.00 to 0.17
0.01
0.00 to 0.27
INS_PREMIX0.07
0.00 to 2.19
4.78
0.07 to 419
1.27
0.01 to 150
INS_PREMIX1.05
0.01 to 135
0.76
0.01 to 94.06
0.55
0.00 to 95.52
0.40
0.00 to 76.49
0.35
0.01 to 13.39
0.20
0.00 to 58.55
0.18
0.00 to 48.64
0.16
0.00 to 42.75
0.14
0.00 to 5.24
0.13
0.00 to 4.70
0.11
0.00 to 32.89
0.10
0.00 to 32.05
0.10
0.00 to 32.67
0.06
0.00 to 0.88
0.05
0.00 to 1.77
0.03
0.00 to 1.32
0.03
0.00 to 1.04
0.02
0.00 to 0.65
0.02
0.00 to 0.65
0.02
0.00 to 0.74
0.02
0.00 to 0.69
0.02
0.00 to 0.91
0.01
0.00 to 0.48
0.01
0.00 to 0.64
0.01
0.00 to 0.49
0.01
0.00 to 0.63
OTHER_ACTIVE_sulfonylurea0.08
0.00 to 0.98
4.71
0.06 to 254
1.18
0.01 to 79.61
0.95
0.01 to 96.56
OTHER_ACTIVE_sulfonylurea0.69
0.01 to 65.33
0.51
0.00 to 69.46
0.37
0.00 to 53.45
0.36
0.01 to 5.89
0.17
0.00 to 33.46
0.17
0.00 to 31.56
0.14
0.00 to 29.83
0.14
0.00 to 2.29
0.13
0.00 to 1.88
0.10
0.00 to 22.04
0.10
0.00 to 20.16
0.10
0.00 to 22.42
0.05
0.00 to 2.71
0.05
0.00 to 0.70
0.03
0.00 to 0.58
0.03
0.00 to 0.46
0.02
0.00 to 0.27
0.02
0.00 to 0.25
0.02
0.00 to 0.36
0.02
0.00 to 0.26
0.02
0.00 to 0.42
0.01
0.00 to 0.24
0.01
0.00 to 0.36
0.01
0.00 to 0.23
0.01
0.00 to 0.32
OTHER_ACTIVE_additional_OAD0.11
0.00 to 1.27
6.94
0.10 to 348
1.75
0.02 to 115
1.32
0.01 to 122
1.46
0.02 to 136
OTHER_ACTIVE_additional_OAD0.72
0.01 to 92.78
0.54
0.00 to 74.15
0.52
0.01 to 7.91
0.26
0.00 to 42.28
0.24
0.00 to 41.57
0.21
0.00 to 33.87
0.20
0.00 to 3.15
0.19
0.00 to 2.95
0.14
0.00 to 32.57
0.14
0.00 to 27.93
0.14
0.00 to 33.70
0.07
0.00 to 3.32
0.08
0.00 to 0.98
0.04
0.00 to 0.79
0.04
0.00 to 0.61
0.03
0.00 to 0.33
0.03
0.00 to 0.39
0.03
0.00 to 0.50
0.03
0.00 to 0.42
0.03
0.00 to 0.58
0.02
0.00 to 0.32
0.01
0.00 to 0.49
0.01
0.00 to 0.35
0.01
0.00 to 0.48
DAPAGLIFLOZIN0.14
0.00 to 3.42
9.15
0.09 to 948
2.25
0.02 to 281
1.81
0.01 to 278
1.95
0.01 to 244
1.40
0.01 to 181
DAPAGLIFLOZIN0.75
0.00 to 136
0.66
0.01 to 21.47
0.35
0.00 to 93.30
0.33
0.00 to 68.20
0.27
0.00 to 77.74
0.25
0.00 to 8.79
0.24
0.00 to 7.96
0.19
0.00 to 67.90
0.20
0.00 to 48.76
0.19
0.00 to 66.50
0.10
0.00 to 7.77
0.09
0.00 to 2.87
0.05
0.00 to 1.96
0.05
0.00 to 1.61
0.04
0.00 to 1.00
0.04
0.00 to 1.06
0.03
0.00 to 1.31
0.04
0.00 to 1.16
0.03
0.00 to 1.48
0.02
0.00 to 0.78
0.02
0.00 to 0.29
0.02
0.00 to 0.81
0.02
0.00 to 0.99
STANDARD_CARE0.19
0.00 to 5.67
12.23
0.11 to 1146
3.02
0.03 to 380
2.53
0.01 to 437
2.68
0.02 to 379
1.84
0.01 to 297
1.33
0.01 to 262
STANDARD_CARE0.91
0.01 to 34.59
0.49
0.00 to 102
0.44
0.00 to 106
0.38
0.00 to 121
0.36
0.00 to 12.78
0.33
0.00 to 11.81
0.26
0.00 to 81.38
0.26
0.00 to 78.83
0.25
0.00 to 92.70
0.13
0.00 to 13.36
0.13
0.00 to 4.34
0.07
0.00 to 3.17
0.07
0.00 to 2.50
0.05
0.00 to 1.66
0.05
0.00 to 1.64
0.05
0.00 to 1.84
0.05
0.00 to 1.69
0.05
0.00 to 2.47
0.03
0.00 to 1.15
0.03
0.00 to 1.78
0.03
0.00 to 1.11
0.02
0.00 to 1.80
SITAGLIPTIN0.21
0.06 to 0.62
13.08
0.99 to 354
3.29
0.24 to 112
2.82
0.07 to 148
2.75
0.17 to 132
1.94
0.13 to 88.24
1.51
0.05 to 93.36
1.09
0.03 to 74.01
SITAGLIPTIN0.55
0.01 to 51.29
0.49
0.00 to 48.50
0.44
0.00 to 48.88
0.39
0.08 to 1.99
0.37
0.07 to 1.60
0.30
0.00 to 37.51
0.29
0.00 to 35.42
0.29
0.00 to 35.07
0.15
0.01 to 3.24
0.15
0.04 to 0.50
0.08
0.02 to 0.25
0.07
0.01 to 0.37
0.06
0.02 to 0.15
0.06
0.01 to 0.19
0.05
0.01 to 0.32
0.06
0.01 to 0.23
0.05
0.01 to 0.40
0.03
0.00 to 0.18
0.03
0.00 to 0.36
0.03
0.00 to 0.21
0.03
0.00 to 0.36
PEGLOX_SC0.38
0.00 to 29.15
26.48
0.17 to 4226
7.06
0.04 to 1393
5.08
0.02 to 1562
5.89
0.03 to 1455
3.83
0.02 to 1035
2.86
0.01 to 931
2.06
0.01 to 559
1.83
0.02 to 167
PEGLOX_SC0.94
0.00 to 417
0.81
0.00 to 397
0.72
0.01 to 68.21
0.65
0.01 to 59.19
0.56
0.00 to 313
0.54
0.00 to 319
0.56
0.00 to 259
0.28
0.00 to 47.46
0.26
0.00 to 20.27
0.14
0.00 to 14.70
0.13
0.00 to 13.02
0.11
0.00 to 8.19
0.10
0.00 to 8.71
0.10
0.00 to 10.05
0.10
0.00 to 8.60
0.10
0.00 to 11.21
0.06
0.00 to 5.70
0.05
0.00 to 7.59
0.05
0.00 to 5.67
0.05
0.00 to 8.35
DAPAEXEN_SC0.42
0.01 to 36.60
29.12
0.16 to 5544
7.11
0.04 to 1708
5.67
0.02 to 2010
5.97
0.03 to 1713
4.11
0.02 to 1341
3.06
0.01 to 1036
2.26
0.01 to 699
2.03
0.02 to 214
1.07
0.00 to 591
DAPAEXEN_SC0.86
0.00 to 520
0.80
0.01 to 82.69
0.73
0.01 to 76.22
0.60
0.00 to 382
0.57
0.00 to 352
0.57
0.00 to 339
0.29
0.00 to 55.97
0.29
0.00 to 28.81
0.15
0.00 to 18.10
0.14
0.00 to 16.73
0.11
0.00 to 9.97
0.11
0.00 to 10.61
0.10
0.00 to 12.42
0.11
0.00 to 10.16
0.10
0.00 to 12.39
0.06
0.00 to 6.71
0.06
0.00 to 8.51
0.06
0.00 to 6.42
0.05
0.00 to 8.01
MEDI41_SC0.48
0.01 to 35.75
31.82
0.20 to 5829
8.13
0.05 to 1907
6.41
0.02 to 2107
7.01
0.03 to 1983
4.83
0.03 to 1206
3.66
0.01 to 1202
2.63
0.01 to 1029
2.30
0.02 to 230
1.24
0.00 to 657
1.17
0.00 to 543
MEDI41_SC0.88
0.01 to 77.26
0.83
0.01 to 76.36
0.69
0.00 to 378
0.70
0.00 to 407
0.66
0.00 to 406
0.34
0.00 to 61.91
0.32
0.00 to 28.78
0.17
0.00 to 18.08
0.16
0.00 to 15.46
0.13
0.00 to 10.39
0.13
0.00 to 10.73
0.12
0.00 to 11.46
0.12
0.00 to 10.58
0.12
0.00 to 13.46
0.07
0.00 to 6.79
0.07
0.00 to 9.17
0.07
0.00 to 6.77
0.06
0.00 to 9.06
DULA_SC0.54
0.15 to 1.80
32.49
3.88 to 723
8.68
0.55 to 332
7.24
0.19 to 363
7.01
0.44 to 326
4.92
0.32 to 226
4.00
0.11 to 255
2.78
0.08 to 210
2.59
0.50 to 13.07
1.39
0.01 to 147
1.26
0.01 to 128
1.14
0.01 to 109
DULA_SC0.94
0.19 to 4.21
0.77
0.01 to 103
0.74
0.01 to 90.97
0.75
0.01 to 99.59
0.40
0.02 to 7.32
0.37
0.09 to 1.50
0.20
0.02 to 1.41
0.19
0.04 to 0.68
0.15
0.04 to 0.51
0.15
0.04 to 0.51
0.14
0.02 to 0.88
0.14
0.03 to 0.55
0.14
0.01 to 1.12
0.08
0.01 to 0.57
0.08
0.00 to 0.98
0.08
0.01 to 0.58
0.07
0.00 to 1.00
OTHER_ACTIVE_investigator_choice_oral_drug0.58
0.17 to 1.84
36.74
2.92 to 953
9.05
0.65 to 355
7.87
0.21 to 362
7.54
0.53 to 332
5.38
0.34 to 255
4.12
0.13 to 259
3.05
0.08 to 206
2.71
0.63 to 13.52
1.55
0.02 to 148
1.38
0.01 to 128
1.21
0.01 to 123
1.06
0.24 to 5.14
OTHER_ACTIVE_investigator_choice_oral_drug0.80
0.01 to 99.22
0.80
0.01 to 87.73
0.81
0.01 to 93.98
0.42
0.02 to 8.89
0.40
0.11 to 1.38
0.21
0.03 to 1.52
0.20
0.04 to 1.08
0.16
0.04 to 0.51
0.16
0.06 to 0.39
0.15
0.02 to 0.89
0.15
0.05 to 0.54
0.14
0.02 to 1.25
0.09
0.01 to 0.57
0.08
0.00 to 0.99
0.08
0.01 to 0.62
0.07
0.00 to 1.08
LIRAMETF_SC0.71
0.01 to 50.68
45.72
0.23 to 8413
12.20
0.06 to 2720
9.29
0.03 to 3007
10.19
0.05 to 2665
7.05
0.03 to 1715
5.20
0.01 to 1556
3.83
0.01 to 1274
3.37
0.03 to 292
1.80
0.00 to 864
1.66
0.00 to 859
1.44
0.00 to 688
1.30
0.01 to 105
1.24
0.01 to 104
LIRAMETF_SC0.98
0.00 to 411
0.98
0.00 to 591
0.48
0.00 to 86.56
0.48
0.00 to 37.53
0.26
0.00 to 26.77
0.24
0.00 to 22.15
0.19
0.00 to 14.03
0.19
0.00 to 14.18
0.17
0.00 to 15.61
0.19
0.00 to 13.64
0.17
0.00 to 18.13
0.10
0.00 to 10.22
0.09
0.00 to 14.03
0.10
0.00 to 10.63
0.08
0.00 to 12.40
METFORMIN0.71
0.01 to 49.61
49.70
0.25 to 7865
12.25
0.06 to 2525
9.71
0.03 to 2768
10.28
0.05 to 2690
7.05
0.04 to 2003
5.09
0.02 to 1673
3.88
0.01 to 1177
3.47
0.03 to 284
1.84
0.00 to 794
1.75
0.00 to 810
1.43
0.00 to 673
1.36
0.01 to 108
1.25
0.01 to 99.23
1.02
0.00 to 423
METFORMIN1.00
0.00 to 537
0.51
0.00 to 81.94
0.49
0.00 to 36.02
0.25
0.00 to 27.62
0.24
0.00 to 20.99
0.19
0.00 to 14.55
0.19
0.00 to 14.48
0.18
0.00 to 15.35
0.19
0.00 to 14.19
0.18
0.00 to 18.72
0.11
0.00 to 9.32
0.10
0.00 to 12.93
0.10
0.00 to 9.56
0.08
0.00 to 12.16
LINAGLIPTIN0.73
0.01 to 55.27
46.83
0.24 to 8851
12.35
0.06 to 3249
9.59
0.03 to 3250
10.30
0.04 to 2612
6.95
0.03 to 1932
5.31
0.02 to 1729
3.95
0.01 to 1187
3.44
0.03 to 284
1.77
0.00 to 869
1.75
0.00 to 952
1.52
0.00 to 795
1.33
0.01 to 121
1.24
0.01 to 111
1.02
0.00 to 558
1.00
0.00 to 491
LINAGLIPTIN0.49
0.00 to 97.28
0.50
0.00 to 42.27
0.26
0.00 to 28.16
0.25
0.00 to 24.20
0.19
0.00 to 15.55
0.20
0.00 to 16.13
0.17
0.00 to 18.15
0.19
0.00 to 16.31
0.18
0.00 to 20.34
0.11
0.00 to 10.33
0.10
0.00 to 14.25
0.10
0.00 to 10.41
0.08
0.00 to 12.20
IGLARLIXI_SC1.41
0.08 to 28.36
84.39
3.99 to 5496
24.00
0.50 to 2029
16.20
1.14 to 936
20.10
0.37 to 1975
13.82
0.30 to 1243
10.18
0.13 to 1345
7.58
0.07 to 1108
6.65
0.31 to 175
3.59
0.02 to 813
3.41
0.02 to 666
2.96
0.02 to 580
2.51
0.14 to 64.86
2.39
0.11 to 59.38
2.10
0.01 to 500
1.94
0.01 to 470
2.02
0.01 to 455
IGLARLIXI_SC0.95
0.05 to 22.65
0.50
0.02 to 16.49
0.47
0.02 to 13.00
0.38
0.02 to 7.80
0.37
0.02 to 8.39
0.34
0.01 to 10.09
0.35
0.02 to 9.01
0.34
0.01 to 12.02
0.21
0.01 to 6.06
0.19
0.00 to 7.98
0.19
0.01 to 6.03
0.17
0.00 to 7.57
EXENER_SC1.46
0.59 to 3.46
89.15
8.19 to 2229
22.99
1.87 to 752
19.47
0.57 to 856
18.97
1.42 to 770
13.33
1.02 to 581
10.64
0.35 to 580
7.65
0.23 to 486
6.82
1.98 to 27.59
3.83
0.05 to 359
3.47
0.03 to 312
3.10
0.03 to 295
2.67
0.67 to 11.22
2.52
0.73 to 9.11
2.09
0.03 to 239
2.05
0.03 to 216
2.00
0.02 to 248
1.05
0.04 to 20.73
EXENER_SC0.53
0.09 to 3.16
0.51
0.11 to 2.28
0.40
0.17 to 0.86
0.40
0.16 to 0.92
0.37
0.06 to 1.97
0.38
0.13 to 1.21
0.36
0.05 to 2.56
0.23
0.03 to 1.22
0.21
0.01 to 2.32
0.21
0.03 to 1.33
0.18
0.01 to 2.45
TASP_SC2.71
0.51 to 14.84
174
9.40 to 5776
43.87
2.39 to 1903
37.96
0.76 to 2096
37.15
1.73 to 1993
25.87
1.26 to 1345
20.03
0.51 to 1471
14.66
0.32 to 1137
12.72
4.00 to 51.69
7.07
0.07 to 856
6.53
0.06 to 712
5.72
0.06 to 731
4.99
0.71 to 41.99
4.75
0.66 to 35.04
3.89
0.04 to 535
3.94
0.04 to 546
3.82
0.04 to 562
1.99
0.06 to 55.89
1.88
0.32 to 11.58
TASP_SC0.95
0.12 to 8.24
0.74
0.14 to 3.79
0.74
0.13 to 4.32
0.69
0.07 to 6.50
0.71
0.11 to 4.80
0.69
0.06 to 7.58
0.41
0.04 to 3.77
0.39
0.02 to 6.29
0.38
0.03 to 4.00
0.34
0.01 to 6.46
TIRZ_SC2.85
0.74 to 11.45
181
15.48 to 4785
45.75
2.97 to 1875
38.69
0.96 to 2113
38.30
2.19 to 1904
26.12
1.65 to 1280
20.82
0.62 to 1471
15.32
0.40 to 1081
13.71
2.69 to 77.14
7.56
0.08 to 815
7.11
0.06 to 704
6.06
0.06 to 668
5.19
1.46 to 24.05
4.97
0.92 to 28.52
4.16
0.05 to 567
4.19
0.05 to 529
3.95
0.04 to 551
2.11
0.08 to 44.55
1.97
0.44 to 9.16
1.05
0.12 to 8.47
TIRZ_SC0.78
0.21 to 3.06
0.78
0.19 to 3.46
0.72
0.08 to 5.43
0.74
0.16 to 3.84
0.71
0.08 to 6.43
0.44
0.05 to 3.35
0.42
0.02 to 5.88
0.40
0.04 to 3.60
0.36
0.01 to 5.78
SEMA_SC3.66
2.08 to 6.79
229
23.41 to 5392
56.53
5.65 to 1834
49.85
1.54 to 2162
48.22
3.72 to 2105
33.53
3.01 to 1326
25.98
1.00 to 1461
19.24
0.60 to 1158
16.97
6.54 to 58.42
9.45
0.12 to 857
8.75
0.10 to 729
7.78
0.10 to 767
6.73
1.97 to 25.03
6.33
1.95 to 22.54
5.20
0.07 to 592
5.13
0.07 to 561
5.19
0.06 to 551
2.64
0.13 to 48.13
2.51
1.16 to 6.06
1.35
0.26 to 7.27
1.28
0.33 to 4.78
SEMA_SC1.00
0.43 to 2.39
0.94
0.16 to 4.38
0.95
0.34 to 2.98
0.92
0.15 to 5.55
0.57
0.10 to 2.69
0.54
0.03 to 5.15
0.52
0.08 to 3.05
0.48
0.01 to 5.65
LIRA_SC3.67
1.71 to 8.07
230
22.47 to 5545
56.88
4.91 to 1947
50.73
1.54 to 2200
46.74
4.05 to 2014
33.81
2.56 to 1469
26.23
0.95 to 1586
19.16
0.61 to 1199
17.13
5.37 to 67.44
9.73
0.11 to 894
8.85
0.09 to 771
7.86
0.09 to 725
6.78
1.97 to 25.14
6.35
2.58 to 16.73
5.15
0.07 to 594
5.25
0.07 to 568
5.11
0.06 to 591
2.69
0.12 to 48.22
2.53
1.09 to 6.14
1.35
0.23 to 7.84
1.28
0.29 to 5.21
1.00
0.42 to 2.32
LIRA_SC0.93
0.15 to 4.57
0.95
0.43 to 2.25
0.91
0.12 to 6.40
0.57
0.09 to 2.87
0.54
0.03 to 5.51
0.52
0.07 to 3.23
0.46
0.01 to 5.77
EFPE_SC3.85
0.99 to 21.06
255
16.93 to 7792
64.29
3.84 to 2787
52.94
1.36 to 2927
54.54
2.77 to 2673
38.73
1.98 to 1822
29.14
0.77 to 2076
20.89
0.54 to 1450
18.86
3.16 to 143
10.52
0.10 to 1236
9.80
0.08 to 1018
8.38
0.09 to 1031
7.31
1.14 to 55.82
6.89
1.13 to 53.60
5.72
0.06 to 735
5.61
0.07 to 721
5.77
0.06 to 783
2.93
0.10 to 68.23
2.68
0.51 to 17.41
1.44
0.15 to 14.49
1.39
0.18 to 11.99
1.07
0.23 to 6.07
1.07
0.22 to 6.60
EFPE_SC1.01
0.20 to 6.61
1.02
0.09 to 10.84
0.61
0.07 to 5.47
0.58
0.02 to 9.56
0.56
0.06 to 5.69
0.49
0.01 to 8.96
SEMA_PO3.89
1.37 to 10.32
241
21.44 to 5856
61.28
4.48 to 2217
52.97
1.45 to 2434
49.58
3.87 to 2186
35.94
2.36 to 1591
27.76
0.86 to 1683
20.08
0.59 to 1397
18.16
4.44 to 78.31
10.19
0.12 to 958
9.25
0.10 to 851
8.15
0.09 to 809
7.03
1.83 to 29.86
6.74
1.84 to 22.07
5.39
0.07 to 643
5.32
0.07 to 617
5.33
0.06 to 657
2.86
0.11 to 52.71
2.66
0.83 to 7.96
1.42
0.21 to 9.02
1.35
0.26 to 6.19
1.05
0.34 to 2.98
1.06
0.44 to 2.34
0.99
0.15 to 5.07
SEMA_PO0.97
0.12 to 7.51
0.60
0.08 to 3.33
0.57
0.03 to 6.18
0.56
0.07 to 3.54
0.49
0.01 to 6.46
ICOSEMA_SC4.01
0.63 to 27.18
256
13.53 to 9474
65.72
3.11 to 3091
56.01
1.10 to 3347
55.76
2.37 to 3184
38.24
1.73 to 2287
29.70
0.68 to 2324
21.01
0.41 to 1944
19.08
2.51 to 168
10.52
0.09 to 1330
10.01
0.08 to 1240
8.21
0.07 to 1230
7.39
0.89 to 70.02
6.99
0.80 to 63.27
5.81
0.06 to 837
5.57
0.05 to 818
5.56
0.05 to 838
2.93
0.08 to 86.22
2.78
0.39 to 20.56
1.45
0.13 to 17.24
1.40
0.16 to 13.23
1.09
0.18 to 6.85
1.10
0.16 to 8.13
0.98
0.09 to 11.33
1.03
0.13 to 8.46
ICOSEMA_SC0.61
0.05 to 7.01
0.59
0.02 to 11.54
0.56
0.05 to 7.23
0.50
0.01 to 11.18
LIXI_SC6.37
1.52 to 35.85
426
25.81 to 14175
106
5.94 to 4881
91.10
2.09 to 4983
91.43
4.12 to 4260
60.47
3.10 to 3519
48.96
1.29 to 3398
35.87
0.87 to 2610
30.66
5.43 to 239
17.24
0.18 to 1820
16.35
0.15 to 1867
13.94
0.15 to 1587
11.95
1.76 to 101
11.26
1.76 to 91.50
9.60
0.10 to 1298
9.38
0.11 to 1304
9.43
0.10 to 1245
4.83
0.17 to 129
4.41
0.82 to 30.63
2.42
0.27 to 24.74
2.27
0.30 to 18.78
1.74
0.37 to 10.51
1.75
0.35 to 11.43
1.64
0.18 to 14.54
1.65
0.30 to 12.46
1.65
0.14 to 19.14
LIXI_SC0.96
0.04 to 15.10
0.91
0.41 to 2.33
0.82
0.02 to 15.57
SAFIGL_PO6.70
0.75 to 113
448
16.64 to 25980
118
4.14 to 9187
96.89
1.56 to 9587
101
2.81 to 7909
69.11
2.06 to 5723
45.54
3.40 to 3566
39.15
0.56 to 4911
32.36
2.74 to 697
18.39
0.13 to 3811
16.95
0.12 to 2796
14.70
0.11 to 2970
12.69
1.02 to 274
11.82
1.01 to 242
10.56
0.07 to 2188
10.22
0.08 to 1767
9.87
0.07 to 2237
5.14
0.13 to 280
4.73
0.43 to 89.41
2.54
0.16 to 60.00
2.41
0.17 to 53.72
1.85
0.19 to 32.10
1.86
0.18 to 34.64
1.72
0.10 to 40.53
1.74
0.16 to 36.07
1.70
0.09 to 45.81
1.04
0.07 to 26.41
SAFIGL_PO0.96
0.06 to 27.29
0.85
0.01 to 35.83
EXEN_SC6.97
1.35 to 44.39
471
24.90 to 16420
114
5.91 to 5403
101
2.04 to 5359
99.77
4.44 to 4761
66.71
2.86 to 3848
51.73
1.24 to 3834
38.55
0.90 to 2988
33.00
4.87 to 289
18.37
0.18 to 2108
17.21
0.16 to 2185
15.15
0.15 to 1789
13.24
1.71 to 122
12.33
1.60 to 106
10.38
0.09 to 1473
10.19
0.10 to 1440
10.28
0.10 to 1406
5.23
0.17 to 151
4.83
0.75 to 38.09
2.60
0.25 to 28.97
2.50
0.28 to 24.44
1.91
0.33 to 12.91
1.92
0.31 to 14.21
1.79
0.18 to 17.53
1.80
0.28 to 14.63
1.78
0.14 to 22.21
1.10
0.43 to 2.45
1.04
0.04 to 17.88
EXEN_SC0.88
0.02 to 17.53
DANU_PO7.60
0.74 to 243
527
16.93 to 46002
136
3.73 to 15573
115
1.59 to 15344
118
3.10 to 12960
80.90
2.07 to 9888
63.39
1.01 to 9949
46.82
0.56 to 7301
38.03
2.81 to 1456
22.12
0.12 to 5159
20.65
0.12 to 4757
17.74
0.11 to 3982
14.72
1.00 to 566
13.84
0.93 to 498
12.47
0.08 to 3471
11.94
0.08 to 3027
11.94
0.08 to 3202
5.93
0.13 to 437
5.53
0.41 to 183
2.95
0.15 to 134
2.78
0.17 to 105
2.10
0.18 to 70.12
2.16
0.17 to 69.48
2.03
0.11 to 74.36
2.06
0.15 to 68.74
1.99
0.09 to 102
1.22
0.06 to 44.58
1.17
0.03 to 69.08
1.14
0.06 to 45.64
DANU_PO

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.199 (95% CrI 0.037 to 0.768), log scale
Residual deviance
86.3 for 102 data points
DIC
136.9 (pD 50.5)
Largest R-hat
1.002
Smallest ESS
bulk 936, tail 1,045
Divergent transitions
0
Convergence
All criteria met
Priors
PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-3.23, 1.79^2) on tau^2 (Withdrawals/drop-outs, pharm vs pharm)

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.

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
TrialSex (percent female)
effect modifier, prognostic factor; 49 of 50
Asian ancestry or region (percent Asian)
effect modifier, prognostic factor; 44 of 50
NCT00754988
S000027
44.918.82
NCT05413369
S000073
47.6100
PIONEER 4
S000133
4813.4
COMBINE 2
S000155
41.8727.65
STEP HFpEF DM
S000161
44.3312.31
NCT01476475
S000191
48.920.62
OUTSTAND-1
S000213
33.09100
NCT01001104
S000232
26.19100
region: all sites in Asia
PIONEER 10
S000234
25.74100
AWARD-7
S000237
47.693.01
SURPASS J-mono
S000239
24.49100
NCT01584232
S000246
28.51100
STARDUST
S000264
21.5not reported
SUSTAIN™ 3
S000329
44.531.75
NCT01029886
S000352
45.4912
SUSTAIN 11
S000363
48.8619.55
NCT00976937
S000415
59.9
100 minus male share
0.6
SUSTAIN 9
S000483
41.7223.51
LIRA-PRIME
S000508
47.5514.6
NCT06589765
S000558
35.68100
region: all sites in Asia
GetGoal-Duo1
S000792
50.2219.5
NCT01558271
S000837
1998.98
SUSTAIN™1
S000878
45.6221.4
LIRA-Ramadan™
S000963
50.7545.14
NCT02200991
S001003
37.5
100 minus male share
100
region: all sites in Asia
LIRA-SWITCH™
S001119
40.5not reported
NCT05514535
S001161
44.199.61
NCT02750410
S001247
38.36100
SUSTAIN
S001311
42.585.03
NCT04552470
S001336
13.51100
GETGOAL-X
S001439
46.321.1
SUSTAIN™
S001498
28.47100
region: all sites in Asia
NCT05486065
S001555
48.691.49
SUSTAIN™ 5
S001872
43.8316.67
SUSTAIN™ 2
S001876
49.3925.1
LIRAFLAME
S001895
15.7not reported
AMPLITUDE-M
S002081
46.061.23
Lixilan-L-CN
S002110
41.81
100 minus male share
100
region: all sites in Asia
NCT03311724
S002256
40.543.6
S002946
S002946
18.7
100 minus male share
100
region: all sites in Asia
S002952
S002952
47100
region: all sites in Asia
S003010
S003010
36.98not reported
S003041
S003041
28.57100
region: all sites in Asia
S003070
S003070
16.67100
region: all sites in Asia
S003071
S003071
34.35100
region: all sites in Asia
S003079
S003079
not reported100
region: all sites in Asia
S003088
S003088
51.44not reported
S003108
S003108
50
100 minus male share
100
region: all sites in Asia
S003426
S003426
62.05100
region: all sites in Asia
S003442
S003442
100not 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, Sex: design means range from 13.5 (DANU_PO vs PLACEBO) to 62.1 (SEMA_SC vs TIRZ_SC) percent female; threshold 15
  • FlagBaseline, Asian ancestry or region: design means range from 1.1 (EXEN_SC vs LIXI_SC) to 100.0 (DANU_PO vs PLACEBO) percent Asian; threshold 30
  • FlagEligibility, hba1c entry range: a design requires hba1c 9 or more while another admits only 8 or less
  • FlagEligibility, bmi entry range: a design requires bmi 35 or more while another admits only 30 or less
  • NoteOutcome assessment, time point: selected time points span 2 to 156 weeks
  • NoteOutcome assessment, analysis set: mixed: completers 1, modified_itt 2, other 2, randomized 5, safety 40
  • NoteOutcome assessment, definition: mixed: ADA severe hypoglycemia 1, gastrointestinal adverse events leading to treatment discontinuation 1, hypoglycemia adverse event, definition not stated 1, hypoglycemia requiring medical assistance 1, hypoglycemia requiring third party assistance 1, level 3 severe hypoglycemia 1, mild hypoglycemia, undefined 1, not stated 32, severe hypoglycemia 1, severe hypoglycemia by ADA classification 1, severe hypoglycemia needing assistance of another person 1, Severe hypoglycemia requiring assistance of another person 1, Severe symptomatic hypoglycemia 1, severe symptomatic hypoglycemia needing assistance 1, severe symptomatic needing assistance with glucose below 2.0 mmol/L or prompt recovery 1, severe, assistance of another person required 1, severe, needing assistance of another person 1, symptomatic hypoglycemia confirmed below 3.3 mmol/L 1, Zero implied by no hypoglycemia of any kind 1
  • NoteOutcome assessment, proportion method: mixed: not stated 48, observed 2
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 1, not stated 46, treatment_policy 1, while_on_treatment 2
  • NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 2, not stated 46, treatment_policy 2
  • NoteRisk of bias, blinding: mixed: double_blind 23, not_reported 2, open_label 21, single_blind 4
  • NoteRisk of bias, funding: mixed: industry 40, mixed 1, non_industry 7, not_reported 2
  • NoteData handling, input conversions: arms_combined 18, count_from_percent 2, printed_denominator 4
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
NCT00754988156safetyhypoglycemia adverse event, definition not statednot statednot statednot statednot statednot stateddouble_blindindustry2008age 18 to 75; HbA1c 7.0 to 10.0 percent; BMI 25 (23 Asian) to 45; metformin at least 1500 mg
NCT0541336924safetynot statednot statednot statednot statedwhile_on_treatmentnot statedopen_labelindustry2022adults 18 or older; T2D 1 year or more; HbA1c 7.5 to 11.0 percent on metformin with or without SGLT2i, or 7.0 to 10.0 percent on metformin plus another OAD; BMI below 40
PIONEER 452safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2016Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more
COMBINE 257safetynot statednot statednot statednot statednot statednot statedopen_labelindustry2022adults T2D on GLP-1 RA with or without oral drugs; HbA1c 7.0 to 10.0 percent
STEP HFpEF DM52safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2021age 18 or older; heart failure with LVEF 45% or more; BMI 30 or more; type 2 diabetes with HbA1c 10% or less
NCT0147647524safetySevere symptomatic hypoglycemianot statednot statednot statednot statednot statedopen_labelindustry2011Adults with T2D; HbA1c 7 to 10 percent on metformin at least 1.5 g/day; insulin naive
OUTSTAND-132safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2024age 18 to 75; HbA1c 7.0 to 10.0 percent; BMI 19.0 to 40.0; diet and exercise only
NCT0100110416safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2009Japanese T2D age 20 to 74; BMI 18.5 to 40; HbA1c 7.0 to 9.5 percent after lead in
PIONEER 1052safetynot statednot statednot statednot statedwhile_on_treatmenttreatment_policysingle_blindindustry2017Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
AWARD-752safetysevere hypoglycemia needing assistance of another personnot statednot statednot statedhypotheticalhypotheticalsingle_blindindustry2012adults with T2D and CKD stage 3 to 4 (eGFR 15 to below 60); HbA1c 7.5 to 10.5 percent on insulin; maximal ACEI or ARB; BMI 23 to 45
SURPASS J-mono52safetynot statednot statednot statednot statedtreatment_policytreatment_policydouble_blindindustry2019Japanese adults 20 or older; BMI 23 or more; HbA1c 7.0 to 10.0 percent; drug naive or oral monotherapy washed out
NCT0158423226safetysevere, needing assistance of another personnot 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
STARDUST26.07safetynot statednot statednot statednot statednot statednot statedsingle_blindnon_industry2021age 35 or older, T2D with PAD, foot TcPO2 30 to 49 mmHg, HbA1c 6.5 to 8 percent
SUSTAIN™ 356safetynot statednot statednot statedobservednot statednot statedopen_labelindustry2013age 18 or older; T2D on stable 1 to 2 oral drugs; HbA1c 7.0 to 10.5 percent; eGFR 60 or more
NCT0102988626modified_ittnot statednot statednot statednot statednot statednot statedopen_labelindustry2010adults 18 or older with type 2 diabetes on oral agents, HbA1c 7.1 to 11.0 percent, BMI 45 or less
SUSTAIN 1152safetynot statednot statednot statednot statednot statednot statedopen_labelindustry2018adults; HbA1c above 7.5 to 10.0 percent on insulin glargine plus metformin
NCT0097693724safetysevere symptomatic hypoglycemia needing assistancenot statednot statednot statednot statednot stateddouble_blindindustry2009age 18 to under 50; BMI 30 or more; HbA1c 7.0 to 10 percent; metformin at least 1.5 g/day
SUSTAIN 936safetynot 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
LIRA-PRIME105safetynot statednot statednot statednot statednot statednot statedopen_labelindustry2016adults; HbA1c 7.5 to 9.0 percent; stable metformin monotherapy
NCT0658976552safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2024age 18 to 75; HbA1c 7.5 to 11.0 percent; BMI 19 to 40; metformin monotherapy; eGFR 45 or more
GetGoal-Duo124safetysymptomatic hypoglycemia confirmed below 3.3 mmol/Lnot statednot statedobservednot statednot stateddouble_blindindustry2009T2D on metformin 1.5 g or more with or without SU, glinide or TZD, HbA1c 7 to 10, BMI over 20; HbA1c 7 to 9 after run in
NCT0155827152safetysevere, assistance of another person requirednot statednot statednot statednot statednot stateddouble_blindindustry2012Japanese; age 20 or more; BMI 18.5 to 35; HbA1c 7.0 to 10.0 percent; OAM naive or OAM stopped
SUSTAIN™135safetysevere hypoglycemia by ADA classificationnot 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
LIRA-Ramadan™30safetynot statednot statednot statednot statednot statednot statedopen_labelindustry2014age 18 to 80; HbA1c 7 to 10 percent; BMI 20 or more; metformin plus sulfonylurea; intent to fast in Ramadan
NCT022009914.43safetynot statednot statednot statednot statednot statednot statedopen_labelindustry2014age 20 to 75; T2D 5 years or more; HbA1c 7.0 to 10.0; FBG 180 mg/dL or less; stable glargine
LIRA-SWITCH™27safetynot statednot statednot statednot statednot statednot stateddouble_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
NCT0551453545safetylevel 3 severe hypoglycemianot statednot statednot statednot statednot statedopen_labelindustry2022adults with T2D, BMI 25 or more, HbA1c 7 to 10 percent, basal insulin up to 40 U/day plus metformin with or without SGLT2i
NCT0275041016safetySevere hypoglycemia requiring assistance of another personnot statednot statednot statednot statednot stateddouble_blindindustry2016Japanese adults 20 years or older; HbA1c 7.5 to 10.5 percent on insulin over 10 U/day; BMI 18.5 to 35
SUSTAIN30safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2017Adults 18 or older, HbA1c 7.0 to 10.5 percent on metformin monotherapy, eGFR 60 or more
NCT0455247012safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2020Japanese adults 20 to 70, diet and exercise only, HbA1c 7 to 10.5 percent, BMI 22.5 to 45.4
GETGOAL-X24safetysevere symptomatic needing assistance with glucose below 2.0 mmol/L or prompt recoverynot statednot statednot statednot statednot statedopen_labelindustry2008age 21 to 84; HbA1c 7 to 10 percent; metformin at least 1.5 g/day
SUSTAIN™62safetygastrointestinal adverse events leading to treatment discontinuationnot statednot statednot statednot statednot statedopen_labelindustry2014Japanese adults 20 or older; HbA1c 7.0 to 10.5 percent; diet and exercise or OAD monotherapy; eGFR 30 or more
NCT0548606549safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2022age 18 to 64; HbA1c 7.0 to 10.5; BMI 27 or more; on metformin
SUSTAIN™ 535safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2014age 18 or older (20 in Japan); HbA1c 7.0 to 10.0 percent; stable basal insulin with or without metformin; eGFR 30 or more
SUSTAIN™ 256safetyADA severe hypoglycemianot statednot statednot statednot statednot stateddouble_blindindustry2013type 2 diabetes on metformin and or thiazolidinedione; HbA1c 7.0 to 10.5 percent
LIRAFLAME26othernot statednot statednot statednot statednot statednot stateddouble_blindmixed2017T2D; age above 50; HbA1c 48 mmol/mol or more; eGFR 30 or more
AMPLITUDE-M56safetynot 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
Lixilan-L-CN30safetynot statednot statednot statednot statednot statednot statedopen_labelindustry2019Chinese adults; HbA1c 7.0 to 10.5 percent; basal insulin 10 to 25 U/day with up to 2 oral drugs; FPG at most 8.9 mmol/L
NCT0331172412modified_ittnot statednot statednot statednot statednot statednot stateddouble_blindindustry2017age 18 to 75; T2D at least 6 months; HbA1c 7.0 to 10.5%; BMI 23 to 45; diet or stable metformin
S00294626randomizedZero implied by no hypoglycemia of any kindnot statednot statednot statednot statednot statedopen_labelnot_reported2020age over 20; T2D on liraglutide 0.6 or 0.9 mg; no new diabetes drug for 3 months
S00295226.07safetynot statednot statednot statednot statednot statednot statednot_reportednon_industry2020age 25 to 65; BMI 24 to 35 or high waist; HbA1c 7 to 14
S00301024safetynot statednot statednot statednot statednot statednot statedopen_labelindustry2017age 18 to 60; BMI 35.0 to 42.5 awaiting bariatric surgery; HbA1c 7.0 to 10.0; eGFR 60 or more
S0030412randomizednot statednot statednot statednot statednot statednot statedopen_labelindustry2014Japanese; age 40 to 70; BMI below 30; HbA1c 6.0 to 8.5 percent
S0030702completerssevere hypoglycemianot statednot statednot statednot statednot statedopen_labelnot_reportednewly diagnosed hospitalized T2D; age 25 to 70; HbA1c 9 to 14 percent; BMI 25 to 35
S00307124randomizedhypoglycemia requiring third party assistancenot statednot statednot statednot statednot statedopen_labelnon_industry2010age 18 to under 80; HbA1c 6.9 to 9.4 percent NGSP; BMI 35 or less; on sulfonylurea
S0030795safetyhypoglycemia requiring medical assistancenot statednot statednot statednot statednot statedopen_labelnon_industry2010age 18 to 80, HbA1c 7.5 to 12 percent, BMI 21 to 35, T2D at least 6 months
S0030886randomizednot statednot statednot statednot statednot statednot stateddouble_blindindustry2015age 18 to 65; type 2 diabetes; BMI 25 to 42 kg/m2; LDL-C 1.81 mmol/L or more; metformin required in Part B
S00310824randomizednot statednot statednot statednot statednot statednot statedsingle_blindnon_industry2012T2D with coronary artery disease; no severe heart failure; creatinine up to 150 umol/L
S00342624safetymild hypoglycemia, undefinednot statednot statednot statednot statednot statedopen_labelnon_industryadults with type 2 diabetes; HbA1c 6.5 to 8.0 percent; BMI 30 to 35; stable metformin and empagliflozin
S00344224othernot statednot statednot statednot statednot statednot statednot_reportednon_industry2019Women with T2D by ADA criteria; no weight loss drugs within 24 weeks

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the hazard ratio (from event counts) on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.
Trial data entering this analysis
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
NCT00754988A2+A3TASP_SC156arm, events73 / 388arms_combinedR0022521:Table 2
NCT00754988A4SITAGLIPTIN156arm, events3 / 185R0022521:Table 2
NCT05413369A1IGLARLIXI_SC24arm, events4 / 291R0013589:Table 1
NCT05413369A2INS_PREMIX24arm, events0 / 291R0013589:Table 1
PIONEER 4A1SEMA_PO52arm, events22 / 285R0015836:Table 3
PIONEER 4A2LIRA_SC52arm, events17 / 284R0015836:Table 3
PIONEER 4A3PLACEBO52arm, events3 / 142R0015836:Table 3
COMBINE 2A1ICOSEMA_SC57arm, events3 / 342R0005851:Results
COMBINE 2A2SEMA_SC57arm, events2 / 341R0005851:Results
STEP HFpEF DMA1SEMA_SC52arm, events20 / 310R0020223:Table 3
STEP HFpEF DMA2PLACEBO52arm, events9 / 306R0020223:Table 3
NCT01476475A1IGLARLIXI_SC24arm, events2 / 161R0021236:p5
NCT01476475A2INS_GLARGINE24arm, events0 / 162R0021236:p5
OUTSTAND-1A1+A2+A3SAFIGL_PO32arm, events5 / 212arms_combinedR0011607:Table 3
OUTSTAND-1A4PLACEBO32arm, events0 / 72R0011607:Table 3
NCT01001104A1PLACEBO16arm, events0 / 37R0015000:Results
NCT01001104A2+A3+A4DULA_SC16arm, events0 / 108arms_combinedR0015000:Results
PIONEER 10A1+A2+A3SEMA_PO52arm, events11 / 393arms_combinedR0018421:Table 2
PIONEER 10A4DULA_SC52arm, events1 / 65R0018421:Table 2
AWARD-7A1INS_GLARGINE52arm, events0 / 194R0017387:Results
AWARD-7A2+A3DULA_SC52arm, events17 / 383arms_combinedR0017387:Results
SURPASS J-monoA1+A2+A3TIRZ_SC52arm, events22 / 477arms_combinedR0012580:Table 3
SURPASS J-monoA4DULA_SC52arm, events1 / 159R0012580:Table 3
NCT01584232A1DULA_SC26arm, events1 / 181R0016159:Results
NCT01584232A2INS_GLARGINE26arm, events0 / 180R0016159:Results
STARDUSTA1LIRA_SC26.07arm, events0 / 30registry:adverse_events
STARDUSTA2STANDARD_CARE26.07arm, events0 / 30registry:adverse_events
SUSTAIN™ 3A1SEMA_SC56arm, events24 / 406count_from_percentR0013158:Supplement Table S4
SUSTAIN™ 3A2EXENER_SC56arm, events12 / 407count_from_percentR0013158:Supplement Table S4
NCT01029886A1EXENER_SC26arm, events6 / 461R0011287:Table 3
NCT01029886A2LIRA_SC26arm, events18 / 451R0011287:Table 3
SUSTAIN 11A1SEMA_SC52arm, events15 / 874R0022346:Table 3
SUSTAIN 11A2INS_ASPART52arm, events0 / 874R0022346:Table 3
NCT00976937A1LIXI_SC24arm, events1 / 158R0012687:Table 2
NCT00976937A2SITAGLIPTIN24arm, events0 / 161R0012687:Table 2
SUSTAIN 9A1SEMA_SC36arm, events10 / 151R0021710:Table 2
SUSTAIN 9A2PLACEBO36arm, events0 / 151R0021710:Table 2
LIRA-PRIMEA1LIRA_SC105arm, events54 / 996R0022482:Supplement Table S7
LIRA-PRIMEA2OTHER_ACTIVE_investigator_choice_oral_drug105arm, events9 / 995R0022482:Supplement Table S7
NCT06589765A1+A2+A3SAFIGL_PO52arm, events20 / 608arms_combinedR0029347:Table 3
NCT06589765A4DAPAGLIFLOZIN52arm, events0 / 202R0029347:Table 3
GetGoal-Duo1A1PLACEBO24arm, events0 / 223R0026107:Results
GetGoal-Duo1A2LIXI_SC24arm, events10 / 223R0026107:Results
NCT01558271A1DULA_SC52arm, events1 / 281R0011754:Results
NCT01558271A2LIRA_SC52arm, events4 / 141R0011754:Results
SUSTAIN™1A1+A2SEMA_SC35arm, events9 / 259arms_combinedR0021710:Table 2
SUSTAIN™1A3PLACEBO35arm, events1 / 129R0021710:Table 2
LIRA-Ramadan™A1LIRA_SC30arm, events11 / 172R0025756:Supplement Table S2
LIRA-Ramadan™A2OTHER_ACTIVE_sulfonylurea30arm, events0 / 171R0025756:Supplement Table S2
NCT02200991A1LIXI_SC4.43arm, events2 / 69R0024589:Results
NCT02200991A2SITAGLIPTIN4.43arm, events0 / 67R0024589:Results
LIRA-SWITCH™A1LIRA_SC27arm, events9 / 203R0025720:Results
LIRA-SWITCH™A2SITAGLIPTIN27arm, events0 / 204R0025720:Results
NCT05514535A1SEMA_SC45arm, events4 / 288R0015842:Table 2
NCT05514535A2INS_GLARGINE45arm, events0 / 285R0015842:Table 2
NCT02750410A1PLACEBO16arm, events0 / 39R0023021:Results
NCT02750410A2DULA_SC16arm, events1 / 120R0023021:Results
SUSTAINA1+A2SEMA_SC30arm, events31 / 578arms_combinedR0014802:Table 3
SUSTAINA3SITAGLIPTIN30arm, events1 / 290R0014802:Table 3
NCT04552470A1PLACEBO12arm, events0 / 9R0004540:Results
NCT04552470A2+A3+A4DANU_PO12arm, events6 / 28arms_combinedR0004540:Results
GETGOAL-XA1LIXI_SC24arm, events20 / 320R0022279:Results
GETGOAL-XA2EXEN_SC24arm, events24 / 319R0022279:Results
SUSTAIN™A1+A2SEMA_SC62arm, events25 / 480arms_combinedR0025024:Figure 1
SUSTAIN™A3OTHER_ACTIVE_additional_OAD62arm, events0 / 121R0025024:Figure 1
NCT05486065A1+A2+A3SEMA_SC49arm, events21 / 185arms_combinedR0005510:Supplement Table 5
NCT05486065A4PLACEBO49arm, events0 / 60R0005510:Supplement Table 5
SUSTAIN™ 5A1+A2SEMA_SC35arm, events9 / 264arms_combinedR0021710:Table 2
SUSTAIN™ 5A3PLACEBO35arm, events0 / 133R0021710:Table 2
SUSTAIN™ 2A1+A2SEMA_SC56arm, events58 / 818printed_denominator;arms_combinedR0021710:Table 2
SUSTAIN™ 2A3SITAGLIPTIN56arm, events3 / 407printed_denominatorR0021710:Table 2
LIRAFLAMEA1LIRA_SC26arm, events7 / 51R0010519:Results
LIRAFLAMEA2PLACEBO26arm, events0 / 51R0010519:Results
AMPLITUDE-MA1+A2+A3EFPE_SC56arm, events24 / 304arms_combinedR0007136:Table 2
AMPLITUDE-MA4PLACEBO56arm, events2 / 102R0007136:Table 2
Lixilan-L-CNA1IGLARLIXI_SC30arm, events2 / 212R0014540:Results
Lixilan-L-CNA2INS_GLARGINE30arm, events0 / 214R0014540:Results
NCT03311724A1PLACEBO12arm, events0 / 26R0010282:Results
NCT03311724A2+A3+A4TIRZ_SC12arm, events2 / 85arms_combinedR0010282:Results
S002946A1SEMA_SC26arm, events1 / 16R0006360:Supplement Table S2
S002946A2DULA_SC26arm, events0 / 16R0006360:Supplement Table S2
S002952A1PEGLOX_SC26.07arm, events0 / 50R0007813:Results
S002952A2STANDARD_CARE26.07arm, events0 / 50R0007813:Results
S003010A1DAPAEXEN_SC24arm, events0 / 26R0010440:Results
S003010A2STANDARD_CARE24arm, events0 / 30R0010440:Results
S003041A1LINAGLIPTIN2arm, events0 / 18R0020035:Supplement Figure S1
S003041A2LIRA_SC2arm, events0 / 17R0020035:Supplement Figure S1
S003070A1STANDARD_CARE2arm, events0 / 30R0024678:p5
S003070A2LIRA_SC2arm, events0 / 30R0024678:p5
S003071A1LIRA_SC24arm, events0 / 50R0023696:Results
S003071A2SITAGLIPTIN24arm, events0 / 49R0023696:Results
S003079A1EXEN_SC5arm, events0 / 18R0025923:Results
S003079A2STANDARD_CARE5arm, events0 / 18R0025923:Results
S003088A1+A2+A3+A4+A5MEDI41_SC6arm, events0 / 30arms_combinedR0026340:Table 3
S003088A6PLACEBO6arm, events0 / 10R0026340:Table 3
S003108A1+A3LIRA_SC24arm, events0 / 60arms_combinedR0025278:Figure 1
S003108A2METFORMIN24arm, events0 / 30R0025278:Figure 1
S003108A4LIRAMETF_SC24arm, events0 / 30R0025278:Figure 1
S003426A1SEMA_SC24arm, events3 / 38R0040396:Table 3
S003426A2TIRZ_SC24arm, events2 / 41R0040396:Table 3
S003442A1DULA_SC24arm, events0 / 48printed_denominatorR0016372:Results
S003442A2LIRA_SC24arm, events0 / 48printed_denominatorR0016372:Results

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