Network meta-analysis
SF-36 physical component summary change
Type 2 diabetes (adults)
weeks 20 to 130 (target week 52)Not stated by the trialsDoses of a drug pooledMean difference
15
Randomized trials
10
Treatments
13,428
Participants
30
Trial arms
In plain language
Across 15 trials with 13,428 participants, 0 of 9 treatments had a clearly better result than placebo on SF-36 physical component summary change, and for 9 the evidence could not tell them apart from placebo. The most favorable estimate was for Canagliflozin: mean difference 1.34 points (95% credible interval -2.08 to 4.97).
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
Mean difference in points. Higher values favor the treatment.
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Canagliflozin CANAGLIFLOZIN | 1.34 (-2.08 to 4.97) | -2.96 to 5.88 | 1.31 (-1.30 to 3.92) | Unclear |
| Semaglutide injection SEMA_SC | 1.12 (-0.93 to 3.40) | -2.19 to 4.74 | 1.11 (-0.49 to 2.71) | Unclear |
| Dulaglutide injection DULA_SC | 1.09 (-2.37 to 4.74) | -3.26 to 5.65 | 1.10 (-1.47 to 3.67) | Unclear |
| Semaglutide tablet SEMA_PO | 0.71 (-0.88 to 2.36) | -2.34 to 3.89 | 0.71 (-0.55 to 1.97) | Unclear |
| Liraglutide injection LIRA_SC | 0.41 (-1.78 to 2.76) | -3.01 to 4.02 | 0.39 (-1.34 to 2.12) | Unclear |
| Insulin aspart (prandial) INS_ASPART | 0.21 (-2.34 to 3.06) | -3.53 to 4.17 | 0.20 (-1.83 to 2.23) | Unclear |
| Sitagliptin SITAGLIPTIN | -0.14 (-3.26 to 3.10) | -4.13 to 4.06 | -0.16 (-2.57 to 2.26) | Unclear |
| Insulin glargine INS_GLARGINE | -0.49 (-3.34 to 2.60) | -4.48 to 3.59 | -0.55 (-2.74 to 1.64) | Unclear |
| Insulin degludec with liraglutide injection IDEGLIRA_SC | -0.58 (-4.23 to 2.85) | -5.19 to 3.73 | -0.68 (-3.40 to 2.03) | 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 | CANAGLIFLOZIN | SEMA_SC | DULA_SC | SEMA_PO | LIRA_SC | INS_ASPART | SITAGLIPTIN | INS_GLARGINE | IDEGLIRA_SC |
|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | -1.34 -4.97 to 2.08 | -1.12 -3.40 to 0.93 | -1.09 -4.74 to 2.37 | -0.71 -2.36 to 0.88 | -0.41 -2.76 to 1.78 | -0.21 -3.06 to 2.34 | 0.14 -3.10 to 3.26 | 0.49 -2.60 to 3.34 | 0.58 -2.85 to 4.23 |
| CANAGLIFLOZIN | 1.34 -2.08 to 4.97 | CANAGLIFLOZIN | 0.21 -2.59 to 3.10 | 0.25 -3.72 to 4.19 | 0.65 -3.19 to 4.62 | 0.91 -2.49 to 4.43 | 1.12 -2.37 to 4.63 | 1.52 -3.28 to 6.30 | 1.84 -1.59 to 5.34 | 1.92 -1.95 to 6.19 |
| SEMA_SC | 1.12 -0.93 to 3.40 | -0.21 -3.10 to 2.59 | SEMA_SC | 0.03 -2.80 to 2.81 | 0.44 -2.25 to 3.18 | 0.73 -1.31 to 2.69 | 0.91 -1.27 to 3.09 | 1.29 -2.69 to 5.08 | 1.62 -0.36 to 3.70 | 1.70 -0.96 to 4.77 |
| DULA_SC | 1.09 -2.37 to 4.74 | -0.25 -4.19 to 3.72 | -0.03 -2.81 to 2.80 | DULA_SC | 0.38 -3.50 to 4.29 | 0.70 -2.84 to 4.20 | 0.90 -2.64 to 4.48 | 1.27 -3.51 to 6.03 | 1.57 -1.73 to 5.19 | 1.67 -2.10 to 5.80 |
| SEMA_PO | 0.71 -0.88 to 2.36 | -0.65 -4.62 to 3.19 | -0.44 -3.18 to 2.25 | -0.38 -4.29 to 3.50 | SEMA_PO | 0.29 -2.55 to 3.10 | 0.49 -2.78 to 3.63 | 0.86 -1.93 to 3.56 | 1.19 -2.16 to 4.52 | 1.27 -2.41 to 5.29 |
| LIRA_SC | 0.41 -1.78 to 2.76 | -0.91 -4.43 to 2.49 | -0.73 -2.69 to 1.31 | -0.70 -4.20 to 2.84 | -0.29 -3.10 to 2.55 | LIRA_SC | 0.19 -1.95 to 2.34 | 0.57 -3.50 to 4.35 | 0.89 -1.96 to 3.73 | 0.99 -2.41 to 4.65 |
| INS_ASPART | 0.21 -2.34 to 3.06 | -1.12 -4.63 to 2.37 | -0.91 -3.09 to 1.27 | -0.90 -4.48 to 2.64 | -0.49 -3.63 to 2.78 | -0.19 -2.34 to 1.95 | INS_ASPART | 0.38 -3.86 to 4.57 | 0.71 -2.25 to 3.72 | 0.79 -2.53 to 4.63 |
| SITAGLIPTIN | -0.14 -3.26 to 3.10 | -1.52 -6.30 to 3.28 | -1.29 -5.08 to 2.69 | -1.27 -6.03 to 3.51 | -0.86 -3.56 to 1.93 | -0.57 -4.35 to 3.50 | -0.38 -4.57 to 3.86 | SITAGLIPTIN | 0.33 -3.83 to 4.69 | 0.41 -4.19 to 5.51 |
| INS_GLARGINE | -0.49 -3.34 to 2.60 | -1.84 -5.34 to 1.59 | -1.62 -3.70 to 0.36 | -1.57 -5.19 to 1.73 | -1.19 -4.52 to 2.16 | -0.89 -3.73 to 1.96 | -0.71 -3.72 to 2.25 | -0.33 -4.69 to 3.83 | INS_GLARGINE | 0.09 -1.88 to 2.28 |
| IDEGLIRA_SC | -0.58 -4.23 to 2.85 | -1.92 -6.19 to 1.95 | -1.70 -4.77 to 0.96 | -1.67 -5.80 to 2.10 | -1.27 -5.29 to 2.41 | -0.99 -4.65 to 2.41 | -0.79 -4.63 to 2.53 | -0.41 -5.51 to 4.19 | -0.09 -2.28 to 1.88 | IDEGLIRA_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.
- FlagEligibility, hba1c entry range: a design requires hba1c 10 or more while another admits only 9.5 or less
- NoteOutcome assessment, time point: selected time points span 26 to 104 weeks
- NoteOutcome assessment, analysis set: mixed: completers 1, full_analysis 13, randomized 1
- NoteOutcome assessment, definition: mixed: not stated 14, overall physical summary norm based score 1
- NoteOutcome assessment, instrument: mixed: not stated 14, SF-36v2 1
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 2, not stated 13
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 2, not stated 13
- NoteRisk of bias, blinding: mixed: double_blind 6, open_label 9
- NoteData handling, input conversions: arms_combined 9, median_converted 2
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SCALE™ Insulin | 56 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | age 18 or older; BMI 27 or higher; HbA1c 6.0 to 10 percent; basal insulin plus up to 2 oral drugs |
| SUSTAIN 11 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2018 | adults; HbA1c above 7.5 to 10.0 percent on insulin glargine plus metformin |
| SUSTAIN 7 | 40 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2016 | age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin background |
| SUSTAIN 10 | 30 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2017 | adults with T2D, HbA1c 7.0 to 11.0 percent on 1 to 3 oral drugs |
| DUAL™ VIII | 26 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2016 | adults with type 2 diabetes uncontrolled on oral drugs, insulin naive |
| PIONEER 7 | 52 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2016 | age 18 or more; HbA1c 7.5 to 9.5 percent; one or two oral glucose lowering drugs |
| NCT05514535 | 40 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2022 | adults with T2D, BMI 25 or more, HbA1c 7 to 10 percent, basal insulin up to 40 U/day plus metformin with or without SGLT2i |
| SUSTAIN™ 4 | 30 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2014 | adults with T2D, insulin naive, on metformin with or without SU; HbA1c 7.0 to 10.0 percent |
| DUALTM IX | 26 | full_analysis | overall physical summary norm based score | SF-36v2 | not stated | not stated | not stated | not stated | open_label | industry | 2016 | adults; insulin naive type 2 diabetes on SGLT2 inhibitor with or without other oral drugs; HbA1c 7.0 to 11.0 percent; BMI 20 to 40 |
| PIONEER 1 | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2016 | adults with type 2 diabetes on diet and exercise only; HbA1c 7.0 to 9.5 percent |
| SUSTAIN 8 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin 1500 mg or maximum tolerated |
| SUSTAIN™ 6 | 104 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2013 | T2D HbA1c 7.0 or more; age 50 or more with CVD, CHF or CKD stage 3 or more, or age 60 or more with CV risk factor |
| PIONEER 5 | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2016 | type 2 diabetes; HbA1c 7.0 to 9.5 percent; moderate renal impairment |
| SIMPLE | 26 | completers | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2014 | age 18 or older; HbA1c 10 or higher; no prandial insulin, DPP-4 inhibitor or GLP-1 RA |
| PIONEER 8 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | adults with type 2 diabetes on basal, premixed or basal bolus insulin 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 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 |
|---|---|---|---|---|---|---|---|---|---|
| SCALE™ Insulin | A1 | LIRA_SC | 56 | arm, change | 2.700 | 0.533 | 198 | registry:outcomes | |
| SCALE™ Insulin | A2 | PLACEBO | 56 | arm, change | 2.200 | 0.512 | 198 | registry:outcomes | |
| SUSTAIN 11 | A1 | SEMA_SC | 52 | arm, change | 1.400 | 0.226 | 803 | registry:outcomes | |
| SUSTAIN 11 | A2 | INS_ASPART | 52 | arm, change | 0.400 | 0.238 | 794 | registry:outcomes | |
| SUSTAIN 7 | A1+A2 | SEMA_SC | 40 | arm, change | 1.624 | 0.283 | 601 | arms_combined | registry:outcomes |
| SUSTAIN 7 | A3+A4 | DULA_SC | 40 | arm, change | 1.610 | 0.276 | 598 | arms_combined | registry:outcomes |
| SUSTAIN 10 | A1 | SEMA_SC | 30 | arm, change | 2.100 | 0.376 | 290 | registry:outcomes | |
| SUSTAIN 10 | A2 | LIRA_SC | 30 | arm, change | 1.400 | 0.348 | 287 | registry:outcomes | |
| DUAL™ VIII | A1 | IDEGLIRA_SC | 26 | arm, change | 1.600 | 0.280 | 506 | registry:outcomes | |
| DUAL™ VIII | A2 | INS_GLARGINE | 26 | arm, change | 0.900 | 0.280 | 506 | registry:outcomes | |
| PIONEER 7 | A1+A3 | SEMA_PO | 52 | arm, change | 1.282 | 0.339 | 346 | arms_combined | registry:outcomes |
| PIONEER 7 | A2+A4 | SITAGLIPTIN | 52 | arm, change | 0.414 | 0.306 | 348 | arms_combined | registry:outcomes |
| NCT05514535 | A1 | SEMA_SC | 40 | arm, change | 3.180 | 0.440 | 288 | registry:outcomes | |
| NCT05514535 | A2 | INS_GLARGINE | 40 | arm, change | 0.120 | 0.395 | 285 | registry:outcomes | |
| SUSTAIN™ 4 | A1+A2 | SEMA_SC | 30 | arm, change | 1.634 | 0.255 | 722 | arms_combined | registry:outcomes |
| SUSTAIN™ 4 | A3 | INS_GLARGINE | 30 | arm, change | 1.180 | 0.340 | 360 | registry:outcomes | |
| DUALTM IX | A1 | IDEGLIRA_SC | 26 | arm, final | 48.325 | 0.709 | 210 | median_converted | registry:outcomes |
| DUALTM IX | A2 | INS_GLARGINE | 26 | arm, final | 49.950 | 0.700 | 210 | median_converted | registry:outcomes |
| PIONEER 1 | A1+A2+A3 | SEMA_PO | 26 | arm, change | 0.671 | 0.267 | 481 | arms_combined | registry:outcomes |
| PIONEER 1 | A4 | PLACEBO | 26 | arm, change | 0.650 | 0.421 | 167 | registry:outcomes | |
| SUSTAIN 8 | A1 | SEMA_SC | 52 | arm, change | 2.700 | 0.338 | 394 | registry:outcomes | |
| SUSTAIN 8 | A2 | CANAGLIFLOZIN | 52 | arm, change | 2.900 | 0.312 | 394 | registry:outcomes | |
| SUSTAIN™ 6 | A1+A2 | SEMA_SC | 104 | arm, change | 1.249 | 0.198 | 1,648 | arms_combined | registry:outcomes |
| SUSTAIN™ 6 | A3+A4 | PLACEBO | 104 | arm, change | 0.210 | 0.198 | 1,649 | arms_combined | registry:outcomes |
| PIONEER 5 | A1 | SEMA_PO | 26 | arm, change | 1.780 | 0.561 | 163 | registry:outcomes | |
| PIONEER 5 | A2 | PLACEBO | 26 | arm, change | -0.150 | 0.481 | 161 | registry:outcomes | |
| SIMPLE | A1 | INS_ASPART | 26 | arm, change | -0.100 | 0.153 | 44 | registry:outcomes | |
| SIMPLE | A2 | LIRA_SC | 26 | arm, change | 0.007 | 0.153 | 46 | registry:outcomes | |
| PIONEER 8 | A1+A2+A3 | SEMA_PO | 52 | arm, change | 0.008 | 0.272 | 547 | arms_combined | registry:outcomes |
| PIONEER 8 | A4 | PLACEBO | 52 | arm, change | -0.410 | 0.482 | 184 | 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.