LivingGLP1
Network meta-analysis

Any cancer

Type 2 diabetes (adults)

longest follow-upRecorded harmsEach dose separatelyHazard ratio (from event counts)Convergence criteria not all met
11
Randomized trials
12
Treatments
15,818
Participants
742
Events

In plain language

Across 11 trials with 15,818 participants, 0 of 11 treatments had a clearly better result than placebo on any cancer, and for 11 the evidence could not tell them apart from placebo. The most favorable estimate was for Dulaglutide 0.75 mg subcutaneous once weekly: hazard ratio (from event counts) 0.29 (95% credible interval 0.00 to 9.14).

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.
DULA_SC_0p75MG_QWDULA_SC_1p5MG_QWEXENER_SC_2MG_QWLIRA_SC_1p8MG_QDOTHER_ACTIVE_additional_OADPLACEBOSEMA_PO_14MG_QDSEMA_PO_3MG_QDSEMA_PO_7MG_QDSEMA_SC_0p5MG_QWSEMA_SC_1p0MG_QWSITAGLIPTIN
Node area shows participants; line width shows trials comparing two treatments directly. Blue: GLP-1 receptor agonist containing treatments; grey: comparators. Hover over or tab to a node or line for details.

Effects compared with Placebo

Hazard ratio (from event counts). Lower values favor the treatment.
0.010.020.050.10.20.250.51245102050← favors treatmentfavors reference →Dulaglutide 0.75 mg subcutaneous…Exenatide extended release 2 mg …Liraglutide 1.8 mg subcutaneous …Semaglutide 0.5 mg subcutaneous …Dulaglutide 1.5 mg subcutaneous …Semaglutide 7 mg oral once daily…Semaglutide 3 mg oral once daily…Semaglutide 1.0 mg subcutaneous …Additional oadSemaglutide 14 mg oral once dail…Sitagliptin
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)Verdict
Dulaglutide 0.75 mg subcutaneous once weekly
DULA_SC_0p75MG_QW
0.29 (0.00 to 9.14)0.00 to 10.96Unclear
Exenatide extended release 2 mg subcutaneous once weekly
EXENER_SC_2MG_QW
0.75 (0.16 to 3.21)0.10 to 4.74Unclear
Liraglutide 1.8 mg subcutaneous once daily
LIRA_SC_1p8MG_QD
0.84 (0.12 to 4.52)0.08 to 6.19Unclear
Semaglutide 0.5 mg subcutaneous once weekly
SEMA_SC_0p5MG_QW
0.98 (0.11 to 6.27)0.07 to 7.94Unclear
Dulaglutide 1.5 mg subcutaneous once weekly
DULA_SC_1p5MG_QW
1.01 (0.32 to 3.22)0.19 to 5.61Unclear
Semaglutide 7 mg oral once daily (original tablet)
SEMA_PO_7MG_QD
1.09 (0.06 to 16.91)0.04 to 21.14Unclear
Semaglutide 3 mg oral once daily (original tablet)
SEMA_PO_3MG_QD
1.12 (0.06 to 16.52)0.04 to 21.23Unclear
Semaglutide 1.0 mg subcutaneous once weekly
SEMA_SC_1p0MG_QW
1.51 (0.30 to 6.71)0.19 to 9.01Unclear
Additional oad
OTHER_ACTIVE_additional_OAD
1.82 (0.19 to 13.12)0.14 to 17.83Unclear
Semaglutide 14 mg oral once daily (original tablet)
SEMA_PO_14MG_QD
2.60 (0.18 to 33.52)0.13 to 43.44Unclear
Sitagliptin
SITAGLIPTIN
3.57 (0.52 to 23.60)0.34 to 31.42Unclear

Ranking

How likely each treatment is to be among the best. Rankings ignore the size of differences and their certainty, so read them with the effects above.

League table

Every treatment against every other: 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 columnPLACEBODULA_SC_0p75MG_QWEXENER_SC_2MG_QWLIRA_SC_1p8MG_QDSEMA_SC_0p5MG_QWDULA_SC_1p5MG_QWSEMA_PO_7MG_QDSEMA_PO_3MG_QDSEMA_SC_1p0MG_QWOTHER_ACTIVE_additional_OADSEMA_PO_14MG_QDSITAGLIPTIN
PLACEBOPLACEBO3.48
0.11 to 240		1.34
0.31 to 6.38		1.19
0.22 to 8.24		1.02
0.16 to 9.27		0.99
0.31 to 3.16		0.92
0.06 to 18.06		0.89
0.06 to 18.12		0.66
0.15 to 3.28		0.55
0.08 to 5.30		0.38
0.03 to 5.58		0.28
0.04 to 1.92
DULA_SC_0p75MG_QW0.29
0.00 to 9.14		DULA_SC_0p75MG_QW0.39
0.00 to 15.86		0.34
0.00 to 17.26		0.30
0.00 to 14.93		0.28
0.00 to 10.89		0.27
0.00 to 14.22		0.28
0.00 to 13.61		0.19
0.00 to 8.23		0.16
0.00 to 9.98		0.12
0.00 to 4.12		0.08
0.00 to 3.57
EXENER_SC_2MG_QW0.75
0.16 to 3.21		2.59
0.06 to 232		EXENER_SC_2MG_QW0.89
0.10 to 8.82		0.75
0.11 to 8.06		0.75
0.10 to 4.56		0.69
0.03 to 17.19		0.68
0.03 to 18.23		0.49
0.11 to 2.44		0.41
0.05 to 4.32		0.29
0.02 to 5.22		0.21
0.02 to 1.83
LIRA_SC_1p8MG_QD0.84
0.12 to 4.52		2.96
0.06 to 250		1.12
0.11 to 9.72		LIRA_SC_1p8MG_QD0.88
0.08 to 11.41		0.84
0.08 to 5.77		0.77
0.03 to 19.95		0.75
0.03 to 21.76		0.56
0.06 to 4.89		0.46
0.03 to 6.70		0.32
0.01 to 7.08		0.23
0.02 to 2.12
SEMA_SC_0p5MG_QW0.98
0.11 to 6.27		3.39
0.07 to 311		1.33
0.12 to 9.16		1.14
0.09 to 12.87		SEMA_SC_0p5MG_QW1.00
0.07 to 7.38		0.90
0.03 to 23.99		0.88
0.03 to 26.04		0.65
0.11 to 2.86		0.53
0.08 to 3.61		0.38
0.01 to 7.69		0.27
0.03 to 2.00
DULA_SC_1p5MG_QW1.01
0.32 to 3.22		3.63
0.09 to 280		1.34
0.22 to 9.72		1.19
0.17 to 11.92		1.00
0.14 to 13.86		DULA_SC_1p5MG_QW0.91
0.05 to 21.44		0.90
0.05 to 23.92		0.65
0.11 to 5.51		0.55
0.06 to 7.69		0.39
0.02 to 7.51		0.28
0.03 to 2.76
SEMA_PO_7MG_QD1.09
0.06 to 16.91		3.74
0.07 to 457		1.44
0.06 to 31.67		1.31
0.05 to 34.60		1.11
0.04 to 33.33		1.10
0.05 to 20.07		SEMA_PO_7MG_QD0.99
0.04 to 23.21		0.73
0.03 to 15.26		0.60
0.02 to 19.68		0.44
0.02 to 5.64		0.30
0.01 to 6.42
SEMA_PO_3MG_QD1.12
0.06 to 16.52		3.61
0.07 to 489		1.48
0.05 to 32.40		1.32
0.05 to 36.01		1.14
0.04 to 31.45		1.11
0.04 to 19.67		1.01
0.04 to 22.70		SEMA_PO_3MG_QD0.74
0.03 to 15.87		0.60
0.02 to 17.99		0.44
0.02 to 5.50		0.31
0.01 to 6.68
SEMA_SC_1p0MG_QW1.51
0.30 to 6.71		5.24
0.12 to 410		2.03
0.41 to 9.04		1.80
0.20 to 16.59		1.53
0.35 to 8.78		1.53
0.18 to 9.04		1.38
0.07 to 33.63		1.36
0.06 to 34.88		SEMA_SC_1p0MG_QW0.83
0.16 to 5.37		0.59
0.03 to 9.90		0.43
0.06 to 2.64
OTHER_ACTIVE_additional_OAD1.82
0.19 to 13.12		6.33
0.10 to 594		2.42
0.23 to 19.79		2.17
0.15 to 29.07		1.88
0.28 to 12.61		1.82
0.13 to 15.76		1.66
0.05 to 54.08		1.66
0.06 to 51.55		1.20
0.19 to 6.32		OTHER_ACTIVE_additional_OAD0.71
0.03 to 16.74		0.51
0.04 to 4.93
SEMA_PO_14MG_QD2.60
0.18 to 33.52		8.32
0.24 to 948		3.43
0.19 to 62.19		3.13
0.14 to 72.40		2.65
0.13 to 68.41		2.56
0.13 to 41.63		2.28
0.18 to 45.17		2.27
0.18 to 41.05		1.70
0.10 to 30.60		1.40
0.06 to 39.88		SEMA_PO_14MG_QD0.72
0.04 to 12.17
SITAGLIPTIN3.57
0.52 to 23.60		13.02
0.28 to 1078		4.79
0.55 to 42.42		4.31
0.47 to 48.56		3.68
0.50 to 37.22		3.59
0.36 to 28.85		3.28
0.16 to 85.33		3.25
0.15 to 83.08		2.35
0.38 to 16.60		1.94
0.20 to 23.79		1.39
0.08 to 24.54		SITAGLIPTIN

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.364 (95% CrI 0.081 to 1.444), log scale
Residual deviance
29.2 for 29 data points
DIC
48.0 (pD 18.8)
Largest R-hat
1.002
Smallest ESS
bulk 1,948, tail 2,637
Divergent transitions
1
Convergence
Not all met; read with caution
Priors
PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2.1, 1.58^2) on tau^2 (Adverse events, 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.

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.
  • NoteOutcome assessment, time point: selected time points span 27 to 365.26 weeks
  • NoteOutcome assessment, analysis set: mixed: randomized 2, safety 9
  • NoteOutcome assessment, definition: mixed: EAC confirmed acute kidney injury 1, minor: symptomatic, glucose below 3.0 mmol/L, not major 1, not stated 4, Severe (ADA) or glucose confirmed below 3.1 mmol/L with symptoms 1, severe (ADA) or symptomatic with plasma glucose below 3.1 mmol/L 1, severe by ADA or plasma glucose below 3.1 mmol/L with symptoms 1, severe hypoglycemia 1, Severe hypoglycemia needing another person to give carbohydrate, glucagon or other measures (protocol) 1
  • NoteOutcome assessment, adjudicated: mixed: not stated 9, yes 2
  • NoteOutcome assessment, proportion method: mixed: not stated 10, observed 1
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 9, treatment_policy 1, while_on_treatment 1
  • NoteOutcome assessment, intercurrent events (rescue): mixed: not stated 10, treatment_policy 1
  • NoteRisk of bias, blinding: mixed: double_blind 7, open_label 3, single_blind 1
Comparability items per trial
Trialblindingtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)fundingstart yearEligibility
NCT02229383double_blind38safetyminor: symptomatic, glucose below 3.0 mmol/L, not majornot statednot statednot statednot statednot statedindustry2014adults; insulin glargine 20 U/d or more with or without metformin; HbA1c 7.0 to 10.5 percent at randomization
REWINDdouble_blind365.26randomizedSevere hypoglycemia needing another person to give carbohydrate, glucagon or other measures (protocol)not statednot statednot statedtreatment_policynot statedindustry2011age 50 or older with T2D; HbA1c 9.5 percent or less; BMI 23 or more; CV disease or risk factors
PIONEER 10single_blind57safetynot statednot statedyesnot statedwhile_on_treatmenttreatment_policyindustry2017Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
SUSTAIN™ 3open_label61safetynot statednot statednot statedobservednot statednot statedindustry2013age 18 or older; T2D on stable 1 to 2 oral drugs; HbA1c 7.0 to 10.5 percent; eGFR 60 or more
REMODELdouble_blind57randomizedsevere hypoglycemianot statednot statednot statednot statednot statedindustry2021T2D with HbA1c 9.0 percent or less; eGFR 30 to 75; UACR 20 to under 5000 mg/g
NCT01617434double_blind27safetynot statednot statednot statednot statednot statednot statedindustry2012age 18 to 80; HbA1c 7.0 to 10.0 percent; BMI 20 to 45; basal insulin analogue 20 U or more with or without metformin
PIONEER 12double_blind31safetyEAC confirmed acute kidney injurynot statedyesnot statednot statednot statedindustry2019adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent
LIRA-SWITCH™double_blind27safetynot statednot statednot statednot statednot statednot statedindustry2013age 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
SUSTAINdouble_blind35safetySevere (ADA) or glucose confirmed below 3.1 mmol/L with symptomsnot statednot statednot statednot statednot statedindustry2017Adults 18 or older, HbA1c 7.0 to 10.5 percent on metformin monotherapy, eGFR 60 or more
SUSTAIN™open_label62safetysevere (ADA) or symptomatic with plasma glucose below 3.1 mmol/Lnot statednot statednot statednot statednot statedindustry2014Japanese adults 20 or older; HbA1c 7.0 to 10.5 percent; diet and exercise or OAD monotherapy; eGFR 30 or more
SUSTAIN™open_label35safetysevere by ADA or plasma glucose below 3.1 mmol/L with symptomsnot statednot statednot statednot statednot statedindustry2014Japanese; age 20 or older; HbA1c 6.5 to 9.5 percent on one OAD or 7.0 to 10.5 percent on diet and exercise

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
REWINDA1PLACEBO365.26arm, events348 / 4,952R0018537:Table 3
REWINDA2DULA_SC_1p5MG_QW365.26arm, events351 / 4,949R0018537:Table 3
PIONEER 10A1SEMA_PO_3MG_QD57arm, events1 / 131R0018421:Table 2
PIONEER 10A2SEMA_PO_7MG_QD57arm, events1 / 132R0018421:Table 2
PIONEER 10A3SEMA_PO_14MG_QD57arm, events1 / 130R0018421:Table 2
PIONEER 10A4DULA_SC_0p75MG_QW57arm, events0 / 65R0018421:Table 2
SUSTAIN™ 3A1SEMA_SC_1p0MG_QW61arm, events8 / 406R0013158:Supplement Table S4
SUSTAIN™ 3A2EXENER_SC_2MG_QW61arm, events2 / 407R0013158:Supplement Table S4
REMODELA1SEMA_SC_1p0MG_QW57arm, events2 / 71R0007381:Extended Data Table 5
REMODELA2PLACEBO57arm, events0 / 35R0007381:Extended Data Table 5
PIONEER 12A1SEMA_PO_3MG_QD31arm, events0 / 361R0019776:ESM Table 4
PIONEER 12A2SEMA_PO_7MG_QD31arm, events0 / 360R0019776:ESM Table 4
PIONEER 12A3SEMA_PO_14MG_QD31arm, events1 / 361R0019776:ESM Table 4
PIONEER 12A4SITAGLIPTIN31arm, events0 / 359R0019776:ESM Table 4
NCT02229383A1EXENER_SC_2MG_QW38arm, events4 / 233R0014763:Table 3
NCT02229383A2PLACEBO38arm, events2 / 231R0014763:Table 3
NCT01617434A1LIRA_SC_1p8MG_QD27arm, events3 / 226R0026247:Table 3
NCT01617434A2PLACEBO27arm, events2 / 225R0026247:Table 3
LIRA-SWITCH™A1LIRA_SC_1p8MG_QD27arm, events0 / 203R0025720:Results
LIRA-SWITCH™A2SITAGLIPTIN27arm, events2 / 204R0025720:Results
SUSTAINA1SEMA_SC_0p5MG_QW35arm, events0 / 288R0014802:Table 3
SUSTAINA2SEMA_SC_1p0MG_QW35arm, events0 / 290R0014802:Table 3
SUSTAINA3SITAGLIPTIN35arm, events2 / 290R0014802:Table 3
SUSTAIN™A1SEMA_SC_0p5MG_QW62arm, events4 / 239R0025024:Table 2
SUSTAIN™A2SEMA_SC_1p0MG_QW62arm, events3 / 241R0025024:Table 2
SUSTAIN™A3OTHER_ACTIVE_additional_OAD62arm, events3 / 121R0025024:Table 2
SUSTAIN™A1SEMA_SC_0p5MG_QW35arm, events0 / 103R0014736:Supplement Table S5
SUSTAIN™A2SEMA_SC_1p0MG_QW35arm, events1 / 102R0014736:Supplement Table S5
SUSTAIN™A3SITAGLIPTIN35arm, events1 / 103R0014736:Supplement Table S5

Rerun this analysis yourself

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