Network meta-analysis
Hospitalization for heart failure
Type 2 diabetes (adults)
longest follow-upCause specific hazardsEach dose separatelyHazard ratio
2
Randomized trials
3
Treatments
0
Participants
4
Trial arms
In plain language
Across 2 trials, 0 of 2 treatments had a clearly better result than placebo on hospitalization for heart failure, and for 2 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 14 mg oral once daily (original tablet): hazard ratio 0.85 (95% credible interval 0.38 to 1.87).
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.
Effects compared with Placebo
Hazard ratio. Lower values favor the treatment.
| Treatment | Bayesian HR (95% CrI) | 95% prediction interval | Frequentist HR (95% CI) | Verdict |
|---|---|---|---|---|
| Semaglutide 14 mg oral once daily (original tablet) SEMA_PO_14MG_QD | 0.85 (0.38 to 1.87) | 0.32 to 2.23 | 0.86 (0.48 to 1.55) | Unclear |
| Exenatide extended release 2 mg subcutaneous once weekly EXENER_SC_2MG_QW | 0.94 (0.51 to 1.70) | 0.38 to 2.25 | 0.94 (0.78 to 1.13) | Unclear |
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 of the row treatment versus the column treatment, posterior median and 95% credible interval. Green: row clearly better; red: row clearly worse.
| Row versus column | PLACEBO | SEMA_PO_14MG_QD | EXENER_SC_2MG_QW |
|---|---|---|---|
| PLACEBO | PLACEBO | 1.18 0.53 to 2.64 | 1.07 0.59 to 1.96 |
| SEMA_PO_14MG_QD | 0.85 0.38 to 1.87 | SEMA_PO_14MG_QD | 0.91 0.33 to 2.37 |
| EXENER_SC_2MG_QW | 0.94 0.51 to 1.70 | 1.10 0.42 to 3.06 | EXENER_SC_2MG_QW |
Heterogeneity, fit and convergence
Bayesian random effects (primary)
Frequentist check (netmeta)
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; the between designs Q above is the global check.
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.
| Trial | Age (years) prognostic factor; 2 of 2 | Established cardiovascular disease (percent of participants) prognostic factor; 1 of 2 |
|---|---|---|
| NCT01144338 S000905 | 61.85 | 73.09 |
| PIONEER 6 S001381 | 66 | not 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, Established cardiovascular disease: not reported by 1 of 2 trials
- FlagOutcome assessment, analysis set: confounded with design: full_analysis 1, randomized 1
- FlagOutcome assessment, definition: confounded with design: death from any cause 1, Hospitalization for heart failure 1
- NoteOutcome assessment, time point: selected time points span 87 to 391.35 weeks
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01144338 | 391.35 | randomized | Hospitalization for heart failure | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2010 | age 18 or older; HbA1c 6.5 to 10.0 percent; eGFR 30 or more |
| PIONEER 6 | 87 | full_analysis | death from any cause | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | T2D; age 50 or more with CVD or CKD, or 60 or more with CV risk factors |
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 on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.
| Trial | Arm | Treatment | Week | Data | Value | SE | Events / N | Flags | Source |
|---|---|---|---|---|---|---|---|---|---|
| NCT01144338 | A1 | PLACEBO | 391.35 | contrast, hr | registry:outcomes | ||||
| NCT01144338 | A2 | EXENER_SC_2MG_QW | 391.35 | contrast, hr | -0.062 | 0.095 | registry:outcomes | ||
| PIONEER 6 | A1 | SEMA_PO_14MG_QD | 87 | contrast, hr | -0.151 | 0.299 | registry:outcomes | ||
| PIONEER 6 | A2 | PLACEBO | 87 | contrast, hr | registry:outcomes |
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.