LivingGLP1
Network meta-analysis

Any cancer

Type 2 diabetes (adults)

longest follow-upRecorded harmsDoses of a drug pooledHazard ratio (from event counts)
11
Randomized trials
8
Treatments
15,818
Participants
742
Events

In plain language

Across 11 trials with 15,818 participants, 0 of 7 treatments had a clearly better result than placebo on any cancer, and for 7 the evidence could not tell them apart from placebo. The most favorable estimate was for Exenatide extended release injection: hazard ratio (from event counts) 0.74 (95% credible interval 0.15 to 3.13).

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_SCEXENER_SCLIRA_SCOTHER_ACTIVE_additional_OADPLACEBOSEMA_POSEMA_SCSITAGLIPTIN
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.
0.10.20.250.51245102050← favors treatmentfavors reference →Exenatide extended release injec…Liraglutide injectionDulaglutide injectionSemaglutide injectionAdditional oadSemaglutide tabletSitagliptin
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
Exenatide extended release injection
EXENER_SC
0.74 (0.15 to 3.13)0.10 to 4.53Unclear
Liraglutide injection
LIRA_SC
0.86 (0.13 to 4.79)0.08 to 6.69Unclear
Dulaglutide injection
DULA_SC
0.97 (0.27 to 2.60)0.14 to 4.40Unclear
Semaglutide injection
SEMA_SC
1.46 (0.30 to 6.79)0.17 to 8.89Unclear
Additional oad
OTHER_ACTIVE_additional_OAD
2.07 (0.20 to 16.28)0.14 to 20.16Unclear
Semaglutide tablet
SEMA_PO
2.77 (0.22 to 47.85)0.17 to 59.02Unclear
Sitagliptin
SITAGLIPTIN
3.93 (0.54 to 25.22)0.35 to 32.70Unclear

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 columnPLACEBOEXENER_SCLIRA_SCDULA_SCSEMA_SCOTHER_ACTIVE_additional_OADSEMA_POSITAGLIPTIN
PLACEBOPLACEBO1.36
0.32 to 6.60		1.16
0.21 to 7.76		1.03
0.39 to 3.76		0.68
0.15 to 3.37		0.48
0.06 to 4.94		0.36
0.02 to 4.57		0.25
0.04 to 1.86
EXENER_SC0.74
0.15 to 3.13		EXENER_SC0.85
0.09 to 9.07		0.78
0.13 to 4.91		0.50
0.11 to 2.44		0.35
0.04 to 3.77		0.26
0.01 to 4.49		0.19
0.02 to 1.63
LIRA_SC0.86
0.13 to 4.79		1.18
0.11 to 11.22		LIRA_SC0.92
0.11 to 7.24		0.58
0.06 to 5.28		0.41
0.03 to 6.89		0.30
0.01 to 6.06		0.23
0.02 to 2.08
DULA_SC0.97
0.27 to 2.60		1.28
0.20 to 7.95		1.09
0.14 to 8.75		DULA_SC0.64
0.10 to 4.17		0.45
0.05 to 5.68		0.34
0.02 to 4.34		0.23
0.03 to 2.17
SEMA_SC1.46
0.30 to 6.79		2.01
0.41 to 9.03		1.73
0.19 to 15.64		1.57
0.24 to 9.58		SEMA_SC0.71
0.14 to 4.19		0.52
0.02 to 8.23		0.38
0.06 to 2.21
OTHER_ACTIVE_additional_OAD2.07
0.20 to 16.28		2.84
0.27 to 23.43		2.42
0.15 to 32.84		2.24
0.18 to 21.09		1.42
0.24 to 7.27		OTHER_ACTIVE_additional_OAD0.71
0.02 to 17.03		0.52
0.05 to 5.71
SEMA_PO2.77
0.22 to 47.85		3.83
0.22 to 84.09		3.33
0.16 to 90.50		2.96
0.23 to 53.84		1.91
0.12 to 42.74		1.40
0.06 to 40.35		SEMA_PO0.72
0.05 to 17.53
SITAGLIPTIN3.93
0.54 to 25.22		5.35
0.61 to 42.83		4.43
0.48 to 47.52		4.29
0.46 to 32.89		2.65
0.45 to 16.77		1.91
0.18 to 21.98		1.39
0.06 to 20.97		SITAGLIPTIN

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.370 (95% CrI 0.075 to 1.459), log scale
Residual deviance
23.2 for 22 data points
DIC
38.9 (pD 15.7)
Largest R-hat
1.001
Smallest ESS
bulk 2,267, tail 2,549
Divergent transitions
0
Convergence
All criteria met
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
  • NoteData handling, input conversions: arms_combined 5
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
REWIND365.26randomizedSevere hypoglycemia needing another person to give carbohydrate, glucagon or other measures (protocol)not statednot statednot statedtreatment_policynot stateddouble_blindindustry2011age 50 or older with T2D; HbA1c 9.5 percent or less; BMI 23 or more; CV disease or risk factors
PIONEER 1057safetynot statednot statedyesnot statedwhile_on_treatmenttreatment_policysingle_blindindustry2017Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
SUSTAIN™ 361safetynot 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
REMODEL57randomizedsevere hypoglycemianot statednot statednot statednot statednot stateddouble_blindindustry2021T2D with HbA1c 9.0 percent or less; eGFR 30 to 75; UACR 20 to under 5000 mg/g
PIONEER 1231safetyEAC confirmed acute kidney injurynot statedyesnot statednot statednot stateddouble_blindindustry2019adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent
NCT0222938338safetyminor: symptomatic, glucose below 3.0 mmol/L, not majornot statednot statednot statednot statednot stateddouble_blindindustry2014adults; insulin glargine 20 U/d or more with or without metformin; HbA1c 7.0 to 10.5 percent at randomization
NCT0161743427safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2012age 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
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
SUSTAIN35safetySevere (ADA) or glucose confirmed below 3.1 mmol/L with symptomsnot statednot statednot statednot statednot stateddouble_blindindustry2017Adults 18 or older, HbA1c 7.0 to 10.5 percent on metformin monotherapy, eGFR 60 or more
SUSTAIN™62safetysevere (ADA) or symptomatic with plasma glucose below 3.1 mmol/Lnot 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
SUSTAIN™35safetysevere by ADA or plasma glucose below 3.1 mmol/L with symptomsnot statednot statednot statednot statednot statedopen_labelindustry2014Japanese; 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_SC365.26arm, events351 / 4,949R0018537:Table 3
PIONEER 10A1+A2+A3SEMA_PO57arm, events3 / 393arms_combinedR0018421:Table 2
PIONEER 10A4DULA_SC57arm, events0 / 65R0018421:Table 2
SUSTAIN™ 3A1SEMA_SC61arm, events8 / 406R0013158:Supplement Table S4
SUSTAIN™ 3A2EXENER_SC61arm, events2 / 407R0013158:Supplement Table S4
REMODELA1SEMA_SC57arm, events2 / 71R0007381:Extended Data Table 5
REMODELA2PLACEBO57arm, events0 / 35R0007381:Extended Data Table 5
PIONEER 12A1+A2+A3SEMA_PO31arm, events1 / 1,082arms_combinedR0019776:ESM Table 4
PIONEER 12A4SITAGLIPTIN31arm, events0 / 359R0019776:ESM Table 4
NCT02229383A1EXENER_SC38arm, events4 / 233R0014763:Table 3
NCT02229383A2PLACEBO38arm, events2 / 231R0014763:Table 3
NCT01617434A1LIRA_SC27arm, events3 / 226R0026247:Table 3
NCT01617434A2PLACEBO27arm, events2 / 225R0026247:Table 3
LIRA-SWITCH™A1LIRA_SC27arm, events0 / 203R0025720:Results
LIRA-SWITCH™A2SITAGLIPTIN27arm, events2 / 204R0025720:Results
SUSTAINA1+A2SEMA_SC35arm, events0 / 578arms_combinedR0014802:Table 3
SUSTAINA3SITAGLIPTIN35arm, events2 / 290R0014802:Table 3
SUSTAIN™A1+A2SEMA_SC62arm, events7 / 480arms_combinedR0025024:Table 2
SUSTAIN™A3OTHER_ACTIVE_additional_OAD62arm, events3 / 121R0025024:Table 2
SUSTAIN™A1+A2SEMA_SC35arm, events1 / 205arms_combinedR0014736:Supplement Table S5
SUSTAIN™A3SITAGLIPTIN35arm, events1 / 103R0014736:Supplement Table S5

Rerun this analysis yourself

Remove treatments or trials and refit the frequentist and Bayesian models in your browser, with the same methods as the published analysis.

Open in the NMA lab