Network meta-analysis
Total daily insulin dose change
Type 1 diabetes
weeks 12 to 40 (target week 26)Not stated by the trialsDoses of a drug pooledMean difference
5
Randomized trials
9
Treatments
212
Participants
13
Trial arms
In plain language
Across 5 trials with 212 participants, 1 of 8 treatments had a clearly better result than placebo on total daily insulin dose change, and for 7 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide injection: mean difference -1.13 units per kg per day (95% credible interval -2.07 to -0.21).
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
Mean difference in units per kg per day. Lower values favor the treatment.
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Semaglutide injection SEMA_SC | -1.13 (-2.07 to -0.21) | -2.10 to -0.19 | -22.60 (-29.00 to -16.20) | Better |
| Empagliflozin EMPAGLIFLOZIN | -0.21 (-1.19 to 0.76) | -1.24 to 0.80 | -19.20 (-27.25 to -11.15) | Unclear |
| Tirzepatide injection TIRZ_SC | -0.19 (-0.41 to 0.04) | -0.48 to 0.14 | -0.19 (-0.29 to -0.09) | Unclear |
| Exenatide extended release injection EXENER_SC | -0.04 (-0.24 to 0.17) | -0.34 to 0.25 | -0.04 (-0.10 to 0.02) | Unclear |
| Exenatide extended release and dapagliflozin injection DAPAEXEN_SC | -0.03 (-0.23 to 0.17) | -0.32 to 0.27 | -0.03 (-0.09 to 0.03) | Unclear |
| Dapagliflozin DAPAGLIFLOZIN | -0.01 (-0.22 to 0.19) | -0.30 to 0.27 | -0.01 (-0.07 to 0.05) | Unclear |
| Standard care or no added treatment STANDARD_CARE | 0.12 (-0.82 to 1.05) | -0.83 to 1.07 | -15.20 (-22.91 to -7.49) | Unclear |
| Liraglutide injection LIRA_SC | 0.36 (-0.59 to 1.36) | -0.62 to 1.38 | 5.83 (-8.01 to 19.67) | 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: mean difference 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_SC | EMPAGLIFLOZIN | TIRZ_SC | EXENER_SC | DAPAEXEN_SC | DAPAGLIFLOZIN | STANDARD_CARE | LIRA_SC |
|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 1.13 0.21 to 2.07 | 0.21 -0.76 to 1.19 | 0.19 -0.04 to 0.41 | 0.04 -0.17 to 0.24 | 0.03 -0.17 to 0.23 | 0.01 -0.19 to 0.22 | -0.12 -1.05 to 0.82 | -0.36 -1.36 to 0.59 |
| SEMA_SC | -1.13 -2.07 to -0.21 | SEMA_SC | -0.92 -2.26 to 0.39 | -0.94 -1.93 to 0.00 | -1.09 -2.06 to -0.14 | -1.10 -2.06 to -0.16 | -1.12 -2.09 to -0.18 | -1.25 -2.55 to 0.06 | -1.49 -2.92 to -0.12 |
| EMPAGLIFLOZIN | -0.21 -1.19 to 0.76 | 0.92 -0.39 to 2.26 | EMPAGLIFLOZIN | -0.02 -1.02 to 0.96 | -0.17 -1.17 to 0.83 | -0.18 -1.18 to 0.80 | -0.20 -1.19 to 0.79 | -0.31 -1.65 to 1.01 | -0.57 -1.93 to 0.78 |
| TIRZ_SC | -0.19 -0.41 to 0.04 | 0.94 -0.00 to 1.93 | 0.02 -0.96 to 1.02 | TIRZ_SC | -0.15 -0.44 to 0.16 | -0.16 -0.46 to 0.14 | -0.18 -0.46 to 0.12 | -0.30 -1.25 to 0.65 | -0.55 -1.55 to 0.43 |
| EXENER_SC | -0.04 -0.24 to 0.17 | 1.09 0.14 to 2.06 | 0.17 -0.83 to 1.17 | 0.15 -0.16 to 0.44 | EXENER_SC | -0.01 -0.24 to 0.20 | -0.03 -0.25 to 0.18 | -0.15 -1.10 to 0.79 | -0.41 -1.40 to 0.58 |
| DAPAEXEN_SC | -0.03 -0.23 to 0.17 | 1.10 0.16 to 2.06 | 0.18 -0.80 to 1.18 | 0.16 -0.14 to 0.46 | 0.01 -0.20 to 0.24 | DAPAEXEN_SC | -0.02 -0.23 to 0.21 | -0.14 -1.11 to 0.81 | -0.39 -1.41 to 0.58 |
| DAPAGLIFLOZIN | -0.01 -0.22 to 0.19 | 1.12 0.18 to 2.09 | 0.20 -0.79 to 1.19 | 0.18 -0.12 to 0.46 | 0.03 -0.18 to 0.25 | 0.02 -0.21 to 0.23 | DAPAGLIFLOZIN | -0.12 -1.08 to 0.83 | -0.37 -1.38 to 0.60 |
| STANDARD_CARE | 0.12 -0.82 to 1.05 | 1.25 -0.06 to 2.55 | 0.31 -1.01 to 1.65 | 0.30 -0.65 to 1.25 | 0.15 -0.79 to 1.10 | 0.14 -0.81 to 1.11 | 0.12 -0.83 to 1.08 | STANDARD_CARE | -0.25 -1.56 to 1.10 |
| LIRA_SC | 0.36 -0.59 to 1.36 | 1.49 0.12 to 2.92 | 0.57 -0.78 to 1.93 | 0.55 -0.43 to 1.55 | 0.41 -0.58 to 1.40 | 0.39 -0.58 to 1.41 | 0.37 -0.60 to 1.38 | 0.25 -1.10 to 1.56 | LIRA_SC |
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.
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 26 weeks
- NoteOutcome assessment, analysis set: mixed: completers 2, modified_itt 1, other 2
- NoteOutcome assessment, definition: mixed: change in HbA1c from week 0 to week 12 1, Change in total daily insulin dose from AID pump data 1, HbA1c value at week 26 1, not stated 2
- NoteRisk of bias, blinding: mixed: double_blind 4, open_label 1
- NoteRisk of bias, funding: mixed: mixed 2, non_industry 2, not_reported 1
- NoteData handling, input conversions: median_converted 2
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ENDIS | 12 | completers | not stated | not stated | not stated | not stated | not stated | not stated | open_label | non_industry | 2021 | type 1 diabetes on MDI or CSII with CGM; HbA1c 9.0 or less; BMI 22 or more; CrCl 60 or more; no atherosclerotic disease |
| TODINELI | 26 | completers | HbA1c value at week 26 | not stated | not stated | not stated | not stated | not stated | double_blind | mixed | 2014 | age over 18; type 1 diabetes 2 years or more; HbA1c 6.5 percent or more; BMI over 22; confirmed polyneuropathy; eGFR 60 or more |
| NCT02962492 | 12 | other | change in HbA1c from week 0 to week 12 | not stated | not stated | not stated | not stated | not stated | double_blind | not_reported | 2016 | established type 1 diabetes on insulin |
| ADJUST-T1D | 26 | other | Change in total daily insulin dose from AID pump data | not stated | not stated | not stated | not stated | not stated | double_blind | mixed | 2023 | age 18 to 65; type 1 diabetes on AID; BMI 30 or more |
| S003007 | 12 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | non_industry | 2024 | age 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 mean difference on the analysis scale against the trial's first row. Flags mark converted, combined or approximated inputs.
| Trial | Arm | Treatment | Week | Data | Value | SE | Events / N | Flags | Source |
|---|---|---|---|---|---|---|---|---|---|
| ENDIS | A1 | EMPAGLIFLOZIN | 12 | arm, change | -5.100 | 1.826 | 30 | R0021681:Table 2 | |
| ENDIS | A2 | SEMA_SC | 12 | arm, change | -8.500 | 1.698 | 30 | R0021681:Table 2 | |
| ENDIS | A3 | STANDARD_CARE | 12 | arm, change | -1.100 | 1.393 | 29 | R0021681:Table 2 | |
| TODINELI | A1 | LIRA_SC | 26 | arm, final | 54.000 | 5.778 | 19 | median_converted | R0012788:Table 3 |
| TODINELI | A2 | PLACEBO | 26 | arm, final | 48.167 | 4.058 | 20 | median_converted | R0012788:Table 3 |
| NCT02962492 | A1 | PLACEBO | 12 | arm, change | -0.010 | 0.020 | 11 | registry:outcomes | |
| NCT02962492 | A2 | DAPAGLIFLOZIN | 12 | arm, change | -0.020 | 0.020 | 15 | registry:outcomes | |
| NCT02962492 | A3 | EXENER_SC | 12 | arm, change | -0.050 | 0.020 | 15 | registry:outcomes | |
| NCT02962492 | A4 | DAPAEXEN_SC | 12 | arm, change | -0.040 | 0.020 | 21 | registry:outcomes | |
| ADJUST-T1D | A1 | SEMA_SC | 26 | arm, change | -17.400 | 2.321 | R0014665:Results | ||
| ADJUST-T1D | A2 | PLACEBO | 26 | arm, change | 5.200 | 2.296 | R0014665:Results | ||
| S003007 | A1 | TIRZ_SC | 12 | arm, change | -0.190 | 0.043 | 11 | R0014500:Table 2 | |
| S003007 | A2 | PLACEBO | 12 | arm, change | 0.000 | 0.023 | 11 | R0014500:Table 2 |
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.