Network meta-analysis
HbA1c below 7 percent
Type 2 diabetes (adults); background therapy: basal insulin with or without non insulin drugs
weeks 36 to 64 (target week 52)Hypothetical (as if everyone stayed on treatment)Doses of a drug pooledOdds ratioSeparate part 2 of a disconnected network
2
Randomized trials
3
Treatments
1,009
Participants
684
Events
In plain language
Across 2 trials with 1,009 participants, 2 of 2 treatments had a clearly better result than placebo on HbA1c below 7 percent. The most favorable estimate was for Tirzepatide injection: odds ratio 30.41 (95% credible interval 3.66 to 92.93).
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 Placebo
Odds ratio. Higher values favor the treatment.
| Treatment | Bayesian OR (95% CrI) | 95% prediction interval | Frequentist OR (95% CI) | Verdict |
|---|---|---|---|---|
| Tirzepatide injection TIRZ_SC | 30.41 (3.66 to 92.93) | 1.85 to 168 | 35.42 (19.27 to 65.11) | Better |
| Orforglipron tablet ORFO_PO | 7.11 (1.20 to 23.45) | 0.63 to 44.15 | 7.68 (4.93 to 11.98) | Better |
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: odds 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 | TIRZ_SC | ORFO_PO |
|---|---|---|---|
| PLACEBO | PLACEBO | 0.03 0.01 to 0.27 | 0.14 0.04 to 0.83 |
| TIRZ_SC | 30.41 3.66 to 92.93 | TIRZ_SC | 4.33 0.46 to 27.29 |
| ORFO_PO | 7.11 1.20 to 23.45 | 0.23 0.04 to 2.19 | ORFO_PO |
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 | Baseline HbA1c (percent) effect modifier, prognostic factor; 2 of 2 | Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 2 of 2 | Diabetes duration (years) effect modifier, prognostic factor; 2 of 2 |
|---|---|---|---|
| ACHIEVE-5 S001044 | 8.5 | S2 | 15 |
| SURPASS-5 S001608 | 8.32 | S2 | 13.3 |
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, analysis set: confounded with design: modified_itt 1, randomized 1
- NoteData handling, input conversions: arms_combined 2, count_from_percent 4
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ACHIEVE-5 | 40 | randomized | not stated | not stated | not stated | not_stated | hypothetical | hypothetical | double_blind | industry | 2023 | adults with T2D on insulin glargine with or without metformin or SGLT2 inhibitor |
| SURPASS-5 | 40 | modified_itt | not stated | not stated | not stated | not_stated | hypothetical | hypothetical | double_blind | industry | 2019 | HbA1c 7.0 to 10.5 percent; BMI 23 or higher; insulin glargine above 0.25 U/kg or 20 U daily with or without metformin |
Trial data
What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the odds 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 |
|---|---|---|---|---|---|---|---|---|---|
| ACHIEVE-5 | A1 | PLACEBO | 40 | arm, responders | 33 / 141 | count_from_percent | registry:outcomes | ||
| ACHIEVE-5 | A2+A3+A4 | ORFO_PO | 40 | arm, responders | 284 / 405 | count_from_percent;arms_combined | registry:outcomes | ||
| SURPASS-5 | A1+A2+A3 | TIRZ_SC | 40 | arm, responders | 327 / 345 | count_from_percent;arms_combined | registry:outcomes | ||
| SURPASS-5 | A4 | PLACEBO | 40 | arm, responders | 40 / 118 | count_from_percent | 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.