Network meta-analysis
Systolic blood pressure change
Type 2 diabetes (adults)
weeks 36 to 64 (target week 52)Hypothetical (as if everyone stayed on treatment)Doses of a drug pooledMean difference
11
Randomized trials
10
Treatments
5,075
Participants
23
Trial arms
In plain language
Across 11 trials with 5,075 participants, 2 of 9 treatments had a clearly better result than placebo on systolic blood pressure change, and for 7 the evidence could not tell them apart from placebo. The most favorable estimate was for Retatrutide injection: mean difference -6.67 mmHg (95% credible interval -13.08 to -0.74).
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 mmHg. Lower values favor the treatment.
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Retatrutide injection RETA_SC | -6.67 (-13.08 to -0.74) | -14.57 to 0.69 | -6.63 (-11.22 to -2.04) | Better |
| Liraglutide injection LIRA_SC | -4.18 (-11.60 to 2.28) | -13.18 to 3.84 | -4.10 (-8.21 to 0.02) | Unclear |
| Orforglipron tablet ORFO_PO | -3.78 (-7.06 to -0.43) | -9.53 to 1.61 | -3.81 (-5.47 to -2.15) | Better |
| Semaglutide injection SEMA_SC | -3.23 (-7.20 to 0.76) | -9.30 to 2.57 | -3.19 (-5.70 to -0.68) | Unclear |
| Semaglutide tablet SEMA_PO | -1.45 (-6.62 to 2.99) | -8.48 to 4.69 | -1.36 (-3.55 to 0.83) | Unclear |
| Dulaglutide injection DULA_SC | -1.06 (-6.44 to 3.56) | -8.53 to 5.24 | -0.92 (-4.19 to 2.36) | Unclear |
| Exenatide extended release injection EXENER_SC | -0.80 (-6.75 to 5.49) | -8.52 to 6.72 | -0.82 (-4.14 to 2.50) | Unclear |
| Additional oad OTHER_ACTIVE_additional_OAD | -0.15 (-6.64 to 6.26) | -8.17 to 7.76 | -0.14 (-3.78 to 3.50) | Unclear |
| Insulin aspart (prandial) INS_ASPART | 0.62 (-5.50 to 6.27) | -7.01 to 7.44 | 0.71 (-2.24 to 3.66) | 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 | RETA_SC | LIRA_SC | ORFO_PO | SEMA_SC | SEMA_PO | DULA_SC | EXENER_SC | OTHER_ACTIVE_additional_OAD | INS_ASPART |
|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 6.67 0.74 to 13.08 | 4.18 -2.28 to 11.60 | 3.78 0.43 to 7.06 | 3.23 -0.76 to 7.20 | 1.45 -2.99 to 6.62 | 1.06 -3.56 to 6.44 | 0.80 -5.49 to 6.75 | 0.15 -6.26 to 6.64 | -0.62 -6.27 to 5.50 |
| RETA_SC | -6.67 -13.08 to -0.74 | RETA_SC | -2.47 -10.24 to 5.69 | -2.88 -9.60 to 3.38 | -3.40 -11.08 to 3.84 | -5.19 -12.12 to 1.59 | -5.57 -11.82 to 0.61 | -5.84 -14.61 to 2.21 | -6.49 -15.41 to 1.89 | -7.28 -15.78 to 1.39 |
| LIRA_SC | -4.18 -11.60 to 2.28 | 2.47 -5.69 to 10.24 | LIRA_SC | -0.38 -7.81 to 6.05 | -0.93 -9.58 to 6.55 | -2.73 -9.49 to 3.82 | -3.14 -7.96 to 1.99 | -3.36 -13.65 to 5.50 | -4.01 -14.07 to 4.98 | -4.81 -14.52 to 4.37 |
| ORFO_PO | -3.78 -7.06 to -0.43 | 2.88 -3.38 to 9.60 | 0.38 -6.05 to 7.81 | ORFO_PO | -0.54 -5.70 to 4.67 | -2.35 -6.13 to 2.18 | -2.70 -7.44 to 2.85 | -3.00 -10.12 to 3.79 | -3.61 -10.73 to 3.55 | -4.42 -10.97 to 2.51 |
| SEMA_SC | -3.23 -7.20 to 0.76 | 3.40 -3.84 to 11.08 | 0.93 -6.55 to 9.58 | 0.54 -4.67 to 5.70 | SEMA_SC | -1.75 -7.58 to 4.74 | -2.14 -8.10 to 4.76 | -2.42 -7.36 to 2.16 | -3.06 -8.13 to 1.91 | -3.88 -8.16 to 1.07 |
| SEMA_PO | -1.45 -6.62 to 2.99 | 5.19 -1.59 to 12.12 | 2.73 -3.82 to 9.49 | 2.35 -2.18 to 6.13 | 1.75 -4.74 to 7.58 | SEMA_PO | -0.40 -4.82 to 4.52 | -0.67 -8.95 to 6.47 | -1.30 -9.51 to 6.13 | -2.13 -9.66 to 5.45 |
| DULA_SC | -1.06 -6.44 to 3.56 | 5.57 -0.61 to 11.82 | 3.14 -1.99 to 7.96 | 2.70 -2.85 to 7.44 | 2.14 -4.76 to 8.10 | 0.40 -4.52 to 4.82 | DULA_SC | -0.23 -8.60 to 7.09 | -0.89 -9.58 to 6.71 | -1.71 -9.85 to 5.88 |
| EXENER_SC | -0.80 -6.75 to 5.49 | 5.84 -2.21 to 14.61 | 3.36 -5.50 to 13.65 | 3.00 -3.79 to 10.12 | 2.42 -2.16 to 7.36 | 0.67 -6.47 to 8.95 | 0.23 -7.09 to 8.60 | EXENER_SC | -0.67 -7.80 to 6.54 | -1.49 -7.58 to 5.31 |
| OTHER_ACTIVE_additional_OAD | -0.15 -6.64 to 6.26 | 6.49 -1.89 to 15.41 | 4.01 -4.98 to 14.07 | 3.61 -3.55 to 10.73 | 3.06 -1.91 to 8.13 | 1.30 -6.13 to 9.51 | 0.89 -6.71 to 9.58 | 0.67 -6.54 to 7.80 | OTHER_ACTIVE_additional_OAD | -0.82 -7.17 to 6.44 |
| INS_ASPART | 0.62 -5.50 to 6.27 | 7.28 -1.39 to 15.78 | 4.81 -4.37 to 14.52 | 4.42 -2.51 to 10.97 | 3.88 -1.07 to 8.16 | 2.13 -5.45 to 9.66 | 1.71 -5.88 to 9.85 | 1.49 -5.31 to 7.58 | 0.82 -6.44 to 7.17 | INS_ASPART |
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 BMI or body weight (kg/m2) effect modifier, prognostic factor; 10 of 11 |
|---|---|
| PIONEER 10 S000234 | 26.26 |
| SUSTAIN™ 3 S000329 | 33.8 |
| SUSTAIN 11 S000363 | 31.55 |
| REMODEL S000395 | 30.8 |
| ACHIEVE-3 S000438 | 35.1 |
| NCT04867785 S000489 | 35.08 |
| NCT01558271 S000837 | 25.51 |
| ACHIEVE-5 S001044 | 30.8 |
| STRIDE S001363 | 28.7 median |
| SUSTAIN™ S001498 | 26.38 |
| ACHIEVE-1 S001950 | body weight 90.2 kg |
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, Baseline BMI or body weight: design means range from 25.5 (DULA_SC vs LIRA_SC) to 35.1 (ORFO_PO vs SEMA_PO) kg/m2; threshold 3
- NoteOutcome assessment, time point: selected time points span 36 to 56 weeks
- NoteOutcome assessment, analysis set: mixed: full_analysis 3, modified_itt 5, randomized 2, safety 1
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 10, not stated 1
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 8, not stated 3
- NoteRisk of bias, blinding: mixed: double_blind 6, open_label 4, single_blind 1
- NoteData handling, input conversions: arms_combined 6, n_randomized 2
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PIONEER 10 | 52 | safety | not stated | not stated | not stated | not stated | hypothetical | hypothetical | single_blind | industry | 2017 | Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug |
| SUSTAIN™ 3 | 56 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2013 | age 18 or older; T2D on stable 1 to 2 oral drugs; HbA1c 7.0 to 10.5 percent; eGFR 60 or more |
| SUSTAIN 11 | 52 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | not stated | open_label | industry | 2018 | adults; HbA1c above 7.5 to 10.0 percent on insulin glargine plus metformin |
| REMODEL | 52 | randomized | not stated | not stated | not stated | not stated | hypothetical | not stated | double_blind | industry | 2021 | T2D with HbA1c 9.0 percent or less; eGFR 30 to 75; UACR 20 to under 5000 mg/g |
| ACHIEVE-3 | 52 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2023 | adults T2D on metformin; HbA1c 7.0 to 10.5 percent |
| NCT04867785 | 36 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2021 | age 18 to 75; HbA1c 7.0 to 10.5 percent; BMI 25 to 50; diet and exercise or stable metformin |
| NCT01558271 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2012 | Japanese; age 20 or more; BMI 18.5 to 35; HbA1c 7.0 to 10.0 percent; OAM naive or OAM stopped |
| 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 |
| STRIDE | 52 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2020 | age 18 or more; type 2 diabetes; symptomatic PAD Fontaine IIa; ABI 0.90 or less or TBI 0.70 or less |
| SUSTAIN™ | 56 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2014 | Japanese adults 20 or older; HbA1c 7.0 to 10.5 percent; diet and exercise or OAD monotherapy; eGFR 30 or more |
| ACHIEVE-1 | 40 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2023 | adults with type 2 diabetes on diet and exercise alone; HbA1c 7.0 to 9.5 percent |
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 | A3 | SEMA_PO | 52 | contrast, md | -1.000 | 1.531 | R0018421:Supplement Table S4 | ||
| PIONEER 10 | A4 | DULA_SC | 52 | contrast, md | R0018421:Supplement Table S4 | ||||
| SUSTAIN™ 3 | A1 | SEMA_SC | 56 | arm, change | -4.600 | 0.680 | 404 | registry:outcomes | |
| SUSTAIN™ 3 | A2 | EXENER_SC | 56 | arm, change | -2.230 | 0.700 | 405 | registry:outcomes | |
| SUSTAIN 11 | A1 | SEMA_SC | 52 | contrast, md | -3.900 | 0.587 | R0022346:Results | ||
| SUSTAIN 11 | A2 | INS_ASPART | 52 | contrast, md | R0022346:Results | ||||
| REMODEL | A1 | SEMA_SC | 52 | contrast, md | -4.000 | 2.883 | R0007381:Extended Data Table 2 | ||
| REMODEL | A2 | PLACEBO | 52 | contrast, md | R0007381:Extended Data Table 2 | ||||
| ACHIEVE-3 | A1+A2 | ORFO_PO | 52 | arm, change | -4.944 | 0.425 | 654 | arms_combined | registry:outcomes |
| ACHIEVE-3 | A3+A4 | SEMA_PO | 52 | arm, change | -2.366 | 0.414 | 681 | arms_combined | registry:outcomes |
| NCT04867785 | A1 | PLACEBO | 36 | arm, change | 0.970 | 2.170 | 45 | R0013029:Supplement Table S4 | |
| NCT04867785 | A2 | DULA_SC | 36 | arm, change | -1.860 | 2.020 | 46 | R0013029:Supplement Table S4 | |
| NCT04867785 | A3+A8 | RETA_SC | 36 | arm, change | -6.687 | 1.513 | 89 | arms_combined | R0013029:Supplement Table S4 |
| NCT01558271 | A1 | DULA_SC | 52 | arm, change | 1.320 | 0.660 | 280 | registry:outcomes | |
| NCT01558271 | A2 | LIRA_SC | 52 | arm, change | -1.860 | 0.950 | 136 | registry:outcomes | |
| ACHIEVE-5 | A1 | PLACEBO | 40 | arm, change | 0.000 | 1.030 | 141 | registry:outcomes | |
| ACHIEVE-5 | A2+A3+A4 | ORFO_PO | 40 | arm, change | -2.424 | 0.644 | 405 | arms_combined | registry:outcomes |
| STRIDE | A1 | SEMA_SC | 52 | arm, change | -4.000 | 0.852 | 310 | registry:outcomes | |
| STRIDE | A2 | PLACEBO | 52 | arm, change | -1.000 | 1.008 | 319 | registry:outcomes | |
| SUSTAIN™ | A1+A2 | SEMA_SC | 56 | arm, change | -2.854 | 0.566 | 480 | n_randomized;arms_combined | R0025024:Table 3 |
| SUSTAIN™ | A3 | OTHER_ACTIVE_additional_OAD | 56 | arm, change | 0.200 | 1.100 | 121 | n_randomized | R0025024:Table 3 |
| ACHIEVE-1 | A1 | PLACEBO | 40 | arm, change | -0.500 | 0.880 | 138 | registry:outcomes | |
| ACHIEVE-1 | A2+A3+A4 | ORFO_PO | 40 | arm, change | -5.081 | 0.539 | 421 | arms_combined | 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.