Network meta-analysis
SF-36 physical component summary change
Type 2 diabetes (adults)
weeks 20 to 130 (target week 52)Treatment policyEach dose separatelyMean difference
2
Randomized trials
5
Treatments
1,863
Participants
6
Trial arms
In plain language
Across 2 trials with 1,863 participants, 0 of 4 treatments had a clearly better result than semaglutide 3 mg oral once daily (original tablet) on SF-36 physical component summary change, and for 4 the evidence could not tell them apart from semaglutide 3 mg oral once daily (original tablet). The most favorable estimate was for Dulaglutide 0.75 mg subcutaneous once weekly: mean difference 0.62 points (95% credible interval -6.71 to 8.39).
Higher 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 Semaglutide 3 mg oral once daily (original tablet)
Mean difference in points. Higher values favor the treatment.
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Dulaglutide 0.75 mg subcutaneous once weekly DULA_SC_0p75MG_QW | 0.62 (-6.71 to 8.39) | -10.14 to 11.76 | 0.55 (-0.77 to 1.86) | Unclear |
| Semaglutide 7 mg oral once daily (original tablet) SEMA_PO_7MG_QD | 0.05 (-7.75 to 7.55) | -10.84 to 10.94 | 0.05 (-0.81 to 0.91) | Unclear |
| Sitagliptin SITAGLIPTIN | 0.03 (-7.05 to 7.56) | -10.74 to 10.94 | 0.00 (-0.84 to 0.84) | Unclear |
| Semaglutide 14 mg oral once daily (original tablet) SEMA_PO_14MG_QD | -0.18 (-7.55 to 7.33) | -10.78 to 10.90 | -0.22 (-1.05 to 0.61) | 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 | SEMA_PO_3MG_QD | DULA_SC_0p75MG_QW | SEMA_PO_7MG_QD | SITAGLIPTIN | SEMA_PO_14MG_QD |
|---|---|---|---|---|---|
| SEMA_PO_3MG_QD | SEMA_PO_3MG_QD | -0.62 -8.39 to 6.71 | -0.05 -7.55 to 7.75 | -0.03 -7.56 to 7.05 | 0.18 -7.33 to 7.55 |
| DULA_SC_0p75MG_QW | 0.62 -6.71 to 8.39 | DULA_SC_0p75MG_QW | 0.57 -10.17 to 12.45 | 0.57 -9.87 to 11.69 | 0.81 -9.92 to 12.01 |
| SEMA_PO_7MG_QD | 0.05 -7.75 to 7.55 | -0.57 -12.45 to 10.17 | SEMA_PO_7MG_QD | 0.04 -8.18 to 8.17 | 0.24 -7.90 to 8.14 |
| SITAGLIPTIN | 0.03 -7.05 to 7.56 | -0.57 -11.69 to 9.87 | -0.04 -8.17 to 8.18 | SITAGLIPTIN | 0.21 -7.31 to 7.69 |
| SEMA_PO_14MG_QD | -0.18 -7.55 to 7.33 | -0.81 -12.01 to 9.92 | -0.24 -8.14 to 7.90 | -0.21 -7.69 to 7.31 | SEMA_PO_14MG_QD |
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.
- FlagOutcome assessment, instrument: confounded with design: not stated 1, SF-36v2 1
- FlagRisk of bias, blinding: confounded with design: double_blind 1, single_blind 1
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PIONEER 10 | 52 | full_analysis | not stated | SF-36v2 | not stated | not stated | treatment_policy | treatment_policy | single_blind | industry | 2017 | Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug |
| PIONEER 3 | 52 | full_analysis | not stated | not stated | not stated | not stated | treatment_policy | treatment_policy | double_blind | industry | 2016 | adults with T2D; HbA1c 7.0 to 10.5 percent; metformin with or without sulfonylurea |
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 |
|---|---|---|---|---|---|---|---|---|---|
| PIONEER 10 | A1 | SEMA_PO_3MG_QD | 52 | contrast, md | -0.550 | 0.671 | R0018421:Supplement Figure S5A | ||
| PIONEER 10 | A4 | DULA_SC_0p75MG_QW | 52 | contrast, md | R0018421:Supplement Figure S5A | ||||
| PIONEER 3 | A1 | SEMA_PO_3MG_QD | 52 | arm, change | 0.310 | 0.301 | 466 | registry:outcomes | |
| PIONEER 3 | A2 | SEMA_PO_7MG_QD | 52 | arm, change | 0.360 | 0.316 | 465 | registry:outcomes | |
| PIONEER 3 | A3 | SEMA_PO_14MG_QD | 52 | arm, change | 0.090 | 0.300 | 465 | registry:outcomes | |
| PIONEER 3 | A4 | SITAGLIPTIN | 52 | arm, change | 0.310 | 0.303 | 467 | 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.