LivingGLP1
Network meta-analysis

Serious adverse events

Type 1 diabetes

longest follow-upRecorded harmsEach dose separatelyHazard ratio (from event counts)
6
Randomized trials
7
Treatments
2,425
Participants
208
Events

In plain language

Across 6 trials with 2,425 participants, 0 of 6 treatments had a clearly better result than placebo on serious adverse events, and for 6 the evidence could not tell them apart from placebo. The most favorable estimate was for Dapagliflozin: hazard ratio (from event counts) 0.52 (95% credible interval 0.01 to 38.46).

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.
DAPAGLIFLOZINLIRA_SC_0p6MG_QDLIRA_SC_1p2MG_QDLIRA_SC_1p8MG_QDPLACEBOSEMA_SC_1p0MG_QWTIRZ_SC_5MG_QW
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 →DapagliflozinTirzepatide 5 mg subcutaneous on…Liraglutide 1.8 mg subcutaneous …Liraglutide 0.6 mg subcutaneous …Liraglutide 1.2 mg subcutaneous …Semaglutide 1.0 mg subcutaneous …
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
Dapagliflozin
DAPAGLIFLOZIN
0.52 (0.01 to 38.46)0.01 to 40.79Unclear
Tirzepatide 5 mg subcutaneous once weekly
TIRZ_SC_5MG_QW
0.52 (0.01 to 41.53)0.01 to 43.88Unclear
Liraglutide 1.8 mg subcutaneous once daily
LIRA_SC_1p8MG_QD
0.82 (0.45 to 1.51)0.34 to 1.97Unclear
Liraglutide 0.6 mg subcutaneous once daily
LIRA_SC_0p6MG_QD
1.07 (0.60 to 1.94)0.44 to 2.63Unclear
Liraglutide 1.2 mg subcutaneous once daily
LIRA_SC_1p2MG_QD
1.12 (0.65 to 2.07)0.49 to 2.72Unclear
Semaglutide 1.0 mg subcutaneous once weekly
SEMA_SC_1p0MG_QW
2.94 (0.12 to 88.28)0.11 to 94.30Unclear

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 columnPLACEBODAPAGLIFLOZINTIRZ_SC_5MG_QWLIRA_SC_1p8MG_QDLIRA_SC_0p6MG_QDLIRA_SC_1p2MG_QDSEMA_SC_1p0MG_QW
PLACEBOPLACEBO1.93
0.03 to 158		1.92
0.02 to 180		1.22
0.66 to 2.22		0.93
0.52 to 1.66		0.89
0.48 to 1.55		0.34
0.01 to 8.43
DAPAGLIFLOZIN0.52
0.01 to 38.46		DAPAGLIFLOZIN0.91
0.00 to 485		0.63
0.01 to 47.80		0.48
0.01 to 38.65		0.47
0.01 to 35.66		0.17
0.00 to 40.10
TIRZ_SC_5MG_QW0.52
0.01 to 41.53		1.10
0.00 to 457		TIRZ_SC_5MG_QW0.64
0.01 to 51.98		0.49
0.01 to 39.13		0.46
0.01 to 37.55		0.17
0.00 to 39.50
LIRA_SC_1p8MG_QD0.82
0.45 to 1.51		1.60
0.02 to 124		1.56
0.02 to 151		LIRA_SC_1p8MG_QD0.77
0.41 to 1.39		0.73
0.39 to 1.31		0.29
0.01 to 7.12
LIRA_SC_0p6MG_QD1.07
0.60 to 1.94		2.08
0.03 to 172		2.02
0.03 to 193		1.29
0.72 to 2.46		LIRA_SC_0p6MG_QD0.95
0.53 to 1.70		0.36
0.01 to 9.60
LIRA_SC_1p2MG_QD1.12
0.65 to 2.07		2.14
0.03 to 188		2.15
0.03 to 199		1.37
0.76 to 2.54		1.05
0.59 to 1.90		LIRA_SC_1p2MG_QD0.38
0.01 to 10.31
SEMA_SC_1p0MG_QW2.94
0.12 to 88.28		5.85
0.02 to 1575		5.84
0.03 to 1622		3.48
0.14 to 112		2.75
0.10 to 85.72		2.60
0.10 to 85.18		SEMA_SC_1p0MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.233 (95% CrI 0.067 to 0.703), log scale
Residual deviance
10.2 for 16 data points
DIC
17.7 (pD 7.5)
Largest R-hat
1.002
Smallest ESS
bulk 3,833, tail 3,519
Divergent transitions
0
Convergence
All criteria met
Priors
PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-1.87, 1.52^2) on tau^2 (Adverse events, pharm vs placebo control)

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 12 to 52 weeks
  • NoteOutcome assessment, definition: mixed: not stated 4, severe hypoglycemia, serious adverse event row 1, severe hypoglycemia, undefined 1
  • NoteRisk of bias, funding: mixed: industry 2, mixed 1, non_industry 1, not_reported 2
  • NoteData handling, input conversions: printed_denominator 2
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
NCT0175336226safetynot statednot statednot statednot statednot statednot stateddouble_blindnot_reported2012type 1 diabetes 1 year or more on insulin; undetectable C-peptide; overweight or obese
ADJUNCT TWO™27safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2014type 1 diabetes at least 12 months; BMI 20 or more; HbA1c 7.0 to 10 percent; basal bolus insulin
NCT0296249212safetysevere hypoglycemia, serious adverse event rownot statednot statednot statednot statednot stateddouble_blindnot_reported2016established type 1 diabetes on insulin
ADJUST-T1D26safetynot statednot statednot statednot statednot statednot stateddouble_blindmixed2023age 18 to 65; type 1 diabetes on AID; BMI 30 or more
ADJUNCT ONE™52safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2013T1D at least 12 months; BMI 20 or higher; HbA1c 7.0 to 10 percent; CSII or basal bolus insulin
S00300712safetysevere hypoglycemia, undefinednot statednot statednot statednot statednot stateddouble_blindnon_industry2024age 18 to 60; type 1 diabetes 2 years or more; BMI 30 or more

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
NCT01753362A1PLACEBO26arm, events0 / 26printed_denominatorregistry:adverse_events
NCT01753362A2LIRA_SC_1p8MG_QD26arm, events0 / 40printed_denominatorregistry:adverse_events
ADJUNCT TWO™A1LIRA_SC_0p6MG_QD27arm, events20 / 212registry:adverse_events
ADJUNCT TWO™A2LIRA_SC_1p2MG_QD27arm, events21 / 209registry:adverse_events
ADJUNCT TWO™A3LIRA_SC_1p8MG_QD27arm, events14 / 207registry:adverse_events
ADJUNCT TWO™A4PLACEBO27arm, events14 / 207registry:adverse_events
NCT02962492A1PLACEBO12arm, events0 / 13registry:adverse_events
NCT02962492A2DAPAGLIFLOZIN12arm, events0 / 17registry:adverse_events
ADJUST-T1DA1SEMA_SC_1p0MG_QW26arm, events1 / 36registry:adverse_events
ADJUST-T1DA2PLACEBO26arm, events0 / 36registry:adverse_events
ADJUNCT ONE™A1LIRA_SC_0p6MG_QD52arm, events35 / 351registry:adverse_events
ADJUNCT ONE™A2LIRA_SC_1p2MG_QD52arm, events36 / 350registry:adverse_events
ADJUNCT ONE™A3LIRA_SC_1p8MG_QD52arm, events29 / 349registry:adverse_events
ADJUNCT ONE™A4PLACEBO52arm, events38 / 348registry:adverse_events
S003007A1TIRZ_SC_5MG_QW12arm, events0 / 12R0014500:Results
S003007A2PLACEBO12arm, events0 / 12R0014500:Results

Rerun this analysis yourself

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