Network meta-analysis
Systolic blood pressure change
Type 2 diabetes (adults)
weeks 20 to 36 (target week 26)Hypothetical (as if everyone stayed on treatment)Doses of a drug pooledMean difference
12
Randomized trials
12
Treatments
3,477
Participants
27
Trial arms
In plain language
Across 12 trials with 3,477 participants, 4 of 11 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 -7.35 mmHg (95% credible interval -12.44 to -2.20).
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 | -7.35 (-12.44 to -2.20) | -12.94 to -1.70 | -7.50 (-12.01 to -2.98) | Better |
| Semaglutide injection SEMA_SC | -6.75 (-10.49 to -3.01) | -11.22 to -2.02 | -6.76 (-9.74 to -3.79) | Better |
| Exenatide extended release and dapagliflozin injection DAPAEXEN_SC | -5.38 (-9.86 to -1.02) | -10.58 to -0.26 | -5.37 (-8.31 to -2.43) | Better |
| Liraglutide injection LIRA_SC | -4.84 (-8.71 to -1.09) | -9.50 to -0.24 | -4.82 (-7.97 to -1.66) | Better |
| Semaglutide tablet SEMA_PO | -4.74 (-10.81 to 1.16) | -11.27 to 2.00 | -4.88 (-9.92 to 0.15) | Unclear |
| Dapagliflozin DAPAGLIFLOZIN | -2.96 (-6.83 to 0.71) | -7.80 to 1.67 | -2.97 (-5.63 to -0.32) | Unclear |
| Sitagliptin SITAGLIPTIN | -2.69 (-6.59 to 1.32) | -7.30 to 2.15 | -2.74 (-5.83 to 0.36) | Unclear |
| Orforglipron tablet ORFO_PO | -2.27 (-6.29 to 1.86) | -7.00 to 2.72 | -2.28 (-5.56 to 0.99) | Unclear |
| Safiglipron (HRS-7535) tablet SAFIGL_PO | -2.21 (-5.98 to 1.48) | -6.86 to 2.35 | -2.15 (-4.90 to 0.60) | Unclear |
| Exenatide extended release injection EXENER_SC | -2.16 (-5.41 to 1.05) | -6.34 to 2.27 | -2.16 (-4.39 to 0.06) | Unclear |
| Dulaglutide injection DULA_SC | -1.81 (-5.74 to 2.17) | -6.70 to 3.14 | -1.88 (-5.50 to 1.73) | 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 | SEMA_SC | DAPAEXEN_SC | LIRA_SC | SEMA_PO | DAPAGLIFLOZIN | SITAGLIPTIN | ORFO_PO | SAFIGL_PO | EXENER_SC | DULA_SC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 7.35 2.20 to 12.44 | 6.75 3.01 to 10.49 | 5.38 1.02 to 9.86 | 4.84 1.09 to 8.71 | 4.74 -1.16 to 10.81 | 2.96 -0.71 to 6.83 | 2.69 -1.32 to 6.59 | 2.27 -1.86 to 6.29 | 2.21 -1.48 to 5.98 | 2.16 -1.05 to 5.41 | 1.81 -2.17 to 5.74 |
| RETA_SC | -7.35 -12.44 to -2.20 | RETA_SC | -0.62 -7.06 to 5.79 | -1.95 -8.54 to 4.89 | -2.51 -8.88 to 3.95 | -2.60 -9.26 to 4.05 | -4.36 -10.59 to 2.10 | -4.61 -11.05 to 1.86 | -5.11 -10.94 to 0.76 | -5.13 -11.30 to 1.30 | -5.20 -11.16 to 0.92 | -5.55 -10.53 to -0.56 |
| SEMA_SC | -6.75 -10.49 to -3.01 | 0.62 -5.79 to 7.06 | SEMA_SC | -1.36 -7.04 to 4.54 | -1.88 -5.37 to 1.82 | -1.99 -8.80 to 5.09 | -3.75 -8.98 to 1.65 | -4.02 -6.42 to -1.59 | -4.48 -9.97 to 1.01 | -4.51 -9.70 to 0.87 | -4.60 -9.57 to 0.35 | -5.00 -10.35 to 0.65 |
| DAPAEXEN_SC | -5.38 -9.86 to -1.02 | 1.95 -4.89 to 8.54 | 1.36 -4.54 to 7.04 | DAPAEXEN_SC | -0.51 -6.47 to 5.26 | -0.61 -7.86 to 6.51 | -2.42 -5.82 to 1.01 | -2.68 -8.83 to 3.17 | -3.15 -9.10 to 2.66 | -3.19 -7.42 to 1.18 | -3.24 -6.64 to 0.14 | -3.56 -9.55 to 2.17 |
| LIRA_SC | -4.84 -8.71 to -1.09 | 2.51 -3.95 to 8.88 | 1.88 -1.82 to 5.37 | 0.51 -5.26 to 6.47 | LIRA_SC | -0.08 -7.14 to 6.95 | -1.86 -7.30 to 3.59 | -2.14 -5.27 to 0.88 | -2.60 -8.32 to 2.94 | -2.64 -8.02 to 2.66 | -2.70 -7.68 to 2.23 | -3.02 -8.62 to 2.44 |
| SEMA_PO | -4.74 -10.81 to 1.16 | 2.60 -4.05 to 9.26 | 1.99 -5.09 to 8.80 | 0.61 -6.51 to 7.86 | 0.08 -6.95 to 7.14 | SEMA_PO | -1.79 -8.53 to 5.23 | -2.06 -9.15 to 4.99 | -2.53 -8.52 to 3.59 | -2.56 -9.44 to 4.56 | -2.61 -9.26 to 4.20 | -2.96 -7.41 to 1.47 |
| DAPAGLIFLOZIN | -2.96 -6.83 to 0.71 | 4.36 -2.10 to 10.59 | 3.75 -1.65 to 8.98 | 2.42 -1.01 to 5.82 | 1.86 -3.59 to 7.30 | 1.79 -5.23 to 8.53 | DAPAGLIFLOZIN | -0.28 -5.86 to 5.09 | -0.72 -6.38 to 4.54 | -0.77 -3.53 to 2.32 | -0.83 -4.04 to 2.31 | -1.14 -6.76 to 4.17 |
| SITAGLIPTIN | -2.69 -6.59 to 1.32 | 4.61 -1.86 to 11.05 | 4.02 1.59 to 6.42 | 2.68 -3.17 to 8.83 | 2.14 -0.88 to 5.27 | 2.06 -4.99 to 9.15 | 0.28 -5.09 to 5.86 | SITAGLIPTIN | -0.49 -6.18 to 5.18 | -0.52 -5.82 to 5.09 | -0.55 -5.58 to 4.49 | -0.92 -6.39 to 4.82 |
| ORFO_PO | -2.27 -6.29 to 1.86 | 5.11 -0.76 to 10.94 | 4.48 -1.01 to 9.97 | 3.15 -2.66 to 9.10 | 2.60 -2.94 to 8.32 | 2.53 -3.59 to 8.52 | 0.72 -4.54 to 6.38 | 0.49 -5.18 to 6.18 | ORFO_PO | -0.04 -5.38 to 5.56 | -0.11 -5.20 to 5.15 | -0.42 -4.51 to 3.63 |
| SAFIGL_PO | -2.21 -5.98 to 1.48 | 5.13 -1.30 to 11.30 | 4.51 -0.87 to 9.70 | 3.19 -1.18 to 7.42 | 2.64 -2.66 to 8.02 | 2.56 -4.56 to 9.44 | 0.77 -2.32 to 3.53 | 0.52 -5.09 to 5.82 | 0.04 -5.56 to 5.38 | SAFIGL_PO | -0.05 -3.97 to 3.71 | -0.42 -5.78 to 4.91 |
| EXENER_SC | -2.16 -5.41 to 1.05 | 5.20 -0.92 to 11.16 | 4.60 -0.35 to 9.57 | 3.24 -0.14 to 6.64 | 2.70 -2.23 to 7.68 | 2.61 -4.20 to 9.26 | 0.83 -2.31 to 4.04 | 0.55 -4.49 to 5.58 | 0.11 -5.15 to 5.20 | 0.05 -3.71 to 3.97 | EXENER_SC | -0.35 -5.45 to 4.79 |
| DULA_SC | -1.81 -5.74 to 2.17 | 5.55 0.56 to 10.53 | 5.00 -0.65 to 10.35 | 3.56 -2.17 to 9.55 | 3.02 -2.44 to 8.62 | 2.96 -1.47 to 7.41 | 1.14 -4.17 to 6.76 | 0.92 -4.82 to 6.39 | 0.42 -3.63 to 4.51 | 0.42 -4.91 to 5.78 | 0.35 -4.79 to 5.45 | DULA_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.
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; 12 of 12 |
|---|---|
| OUTSTAND-1 S000213 | 27.83 |
| PIONEER 10 S000234 | 26.26 |
| NCT04867785 S000489 | 35.08 |
| NCT06589765 S000558 | 27.12 |
| NCT02229383 S000703 | 33.7 |
| NCT02229396 S000791 | 32.73 |
| LIRA-SWITCH™ S001119 | 31.95 |
| SUSTAIN S001311 | 27.8 |
| SUSTAIN™ 5 S001872 | 32.2 |
| SUSTAIN™ S002082 | 25.43 |
| NCT05048719 S002265 | 35.11 |
| NCT02113332 S002357 | 33.6 |
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 26.3 (DULA_SC vs SEMA_PO) to 35.1 (DULA_SC vs ORFO_PO vs PLACEBO) kg/m2; threshold 3
- NoteOutcome assessment, time point: selected time points span 24 to 32 weeks
- NoteOutcome assessment, analysis set: mixed: full_analysis 5, modified_itt 4, randomized 2, safety 1
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 11, not stated 1
- NoteRisk of bias, blinding: mixed: double_blind 10, open_label 1, single_blind 1
- NoteData handling, input conversions: arms_combined 5
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OUTSTAND-1 | 32 | randomized | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2024 | age 18 to 75; HbA1c 7.0 to 10.0 percent; BMI 19.0 to 40.0; diet and exercise only |
| PIONEER 10 | 26 | 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 |
| NCT04867785 | 24 | 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 |
| NCT06589765 | 32 | randomized | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2024 | age 18 to 75; HbA1c 7.5 to 11.0 percent; BMI 19 to 40; metformin monotherapy; eGFR 45 or more |
| NCT02229383 | 28 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2014 | adults; insulin glargine 20 U/d or more with or without metformin; HbA1c 7.0 to 10.5 percent at randomization |
| NCT02229396 | 28 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2014 | age 18 or older; HbA1c 8.0 to 12.0 percent on metformin 1500 mg/d or more |
| LIRA-SWITCH™ | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2013 | age 18 or more; HbA1c 7.5 to 9.5 percent; BMI 20 or more; on sitagliptin 100 mg and metformin for 90 days or more |
| SUSTAIN | 30 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2017 | Adults 18 or older, HbA1c 7.0 to 10.5 percent on metformin monotherapy, eGFR 60 or more |
| SUSTAIN™ 5 | 30 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2014 | age 18 or older (20 in Japan); HbA1c 7.0 to 10.0 percent; stable basal insulin with or without metformin; eGFR 30 or more |
| SUSTAIN™ | 30 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2014 | Japanese; age 20 or older; HbA1c 6.5 to 9.5 percent on one OAD or 7.0 to 10.5 percent on diet and exercise |
| NCT05048719 | 26 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2021 | adults with type 2 diabetes, HbA1c 7.0 to 10.5 percent, BMI 23 or more, diet or metformin |
| NCT02113332 | 24 | full_analysis | not stated | not stated | not stated | not stated | not stated | hypothetical | double_blind | industry | 2013 | T2D on multiple daily insulin injections; HbA1c 7.5 to 11.5 percent; BMI 27.5 to 45 kg/m2 |
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 |
|---|---|---|---|---|---|---|---|---|---|
| OUTSTAND-1 | A3 | SAFIGL_PO | 32 | contrast, md | -2.850 | 2.074 | R0011607:Results | ||
| OUTSTAND-1 | A4 | PLACEBO | 32 | contrast, md | R0011607:Results | ||||
| PIONEER 10 | A3 | SEMA_PO | 26 | contrast, md | -3.000 | 1.786 | R0018421:Supplement Table S4 | ||
| PIONEER 10 | A4 | DULA_SC | 26 | contrast, md | R0018421:Supplement Table S4 | ||||
| NCT04867785 | A1 | PLACEBO | 24 | arm, change | 0.240 | 2.150 | 45 | R0013029:Supplement Table S4 | |
| NCT04867785 | A2 | DULA_SC | 24 | arm, change | -1.150 | 2.020 | 46 | R0013029:Supplement Table S4 | |
| NCT04867785 | A3+A8 | RETA_SC | 24 | arm, change | -6.993 | 1.478 | 89 | arms_combined | R0013029:Supplement Table S4 |
| NCT06589765 | A1+A2+A3 | SAFIGL_PO | 32 | arm, change | -3.665 | 0.451 | 449 | arms_combined | R0029347:Results |
| NCT06589765 | A4 | DAPAGLIFLOZIN | 32 | arm, change | -4.610 | 0.722 | 183 | R0029347:Results | |
| NCT02229383 | A1 | EXENER_SC | 28 | arm, change | -2.600 | 0.900 | 231 | R0014763:Table 2 | |
| NCT02229383 | A2 | PLACEBO | 28 | arm, change | -0.700 | 0.900 | 230 | R0014763:Table 2 | |
| NCT02229396 | A1 | DAPAEXEN_SC | 28 | arm, change | -4.300 | 0.800 | 228 | R0024738:Results | |
| NCT02229396 | A2 | EXENER_SC | 28 | arm, change | -1.200 | 0.800 | 227 | R0024738:Results | |
| NCT02229396 | A3 | DAPAGLIFLOZIN | 28 | arm, change | -1.800 | 0.800 | 230 | R0024738:Results | |
| LIRA-SWITCH™ | A1 | LIRA_SC | 26 | contrast, md | -1.870 | 1.227 | R0025720:Results | ||
| LIRA-SWITCH™ | A2 | SITAGLIPTIN | 26 | contrast, md | R0025720:Results | ||||
| SUSTAIN | A1+A2 | SEMA_SC | 30 | arm, change | -4.953 | 0.647 | 477 | arms_combined | registry:outcomes |
| SUSTAIN | A3 | SITAGLIPTIN | 30 | arm, change | -0.900 | 0.853 | 254 | registry:outcomes | |
| SUSTAIN™ 5 | A2 | SEMA_SC | 30 | contrast, md | -6.290 | 1.850 | R0012671:Results | ||
| SUSTAIN™ 5 | A3 | PLACEBO | 30 | contrast, md | R0012671:Results | ||||
| SUSTAIN™ | A1+A2 | SEMA_SC | 30 | arm, change | -7.041 | 0.821 | 205 | arms_combined | R0014736:Table 3 |
| SUSTAIN™ | A3 | SITAGLIPTIN | 30 | arm, change | -2.800 | 1.100 | 103 | R0014736:Table 3 | |
| NCT05048719 | A1 | PLACEBO | 26 | arm, change | -5.800 | 1.658 | 54 | R0004295:Supplement Table 1 | |
| NCT05048719 | A2+A3+A4+A5+A7 | ORFO_PO | 26 | arm, change | -8.239 | 0.755 | 257 | arms_combined | R0004295:Supplement Table 1 |
| NCT05048719 | A9 | DULA_SC | 26 | arm, change | -8.000 | 1.684 | 50 | R0004295:Supplement Table 1 | |
| NCT02113332 | A1 | LIRA_SC | 24 | arm, change | -4.620 | 1.530 | 61 | R0026157:Table 2 | |
| NCT02113332 | A2 | PLACEBO | 24 | arm, change | 0.860 | 1.570 | 58 | R0026157: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.