Network meta-analysis
SF-36 physical component summary change
Type 2 diabetes (adults)
weeks 20 to 130 (target week 52)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean differenceSeparate part 2 of a disconnected network
11
Randomized trials
14
Treatments
5,454
Participants
36
Trial arms
In plain language
Across 11 trials with 5,454 participants, 1 of 13 treatments had a clearly better result than placebo on SF-36 physical component summary change, and for 12 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 0.5 mg subcutaneous once weekly: mean difference 1.30 points (95% credible interval -0.01 to 2.62).
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 |
|---|---|---|---|---|
| Semaglutide 0.5 mg subcutaneous once weekly SEMA_SC_0p5MG_QW | 1.30 (-0.01 to 2.62) | -0.17 to 2.75 | 1.31 (0.14 to 2.47) | Unclear |
| Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW | 1.13 (0.11 to 2.17) | -0.02 to 2.36 | 1.13 (0.24 to 2.03) | Better |
| Exenatide extended release 2 mg subcutaneous once weekly EXENER_SC_2MG_QW | 0.68 (-0.95 to 2.31) | -1.01 to 2.44 | 0.67 (-0.75 to 2.09) | Unclear |
| Liraglutide 0.9 mg injection once daily LIRA_SC_0p9MG_QD | 0.18 (-1.13 to 1.52) | -1.28 to 1.71 | 0.18 (-1.05 to 1.41) | Unclear |
| Insulin aspart (prandial) INS_ASPART | 0.17 (-1.14 to 1.54) | -1.23 to 1.63 | 0.18 (-0.88 to 1.25) | Unclear |
| Dulaglutide 0.75 mg subcutaneous once weekly DULA_SC_0p75MG_QW | 0.11 (-1.65 to 1.83) | -1.75 to 1.93 | 0.13 (-1.46 to 1.72) | Unclear |
| Orforglipron 12 mg oral once daily ORFO_PO_12MG_QD | 0.08 (-0.75 to 0.92) | -0.95 to 1.12 | 0.08 (-0.69 to 0.85) | Unclear |
| Sitagliptin SITAGLIPTIN | -0.03 (-0.97 to 0.92) | -1.14 to 1.11 | -0.02 (-0.83 to 0.80) | Unclear |
| Semaglutide 14 mg oral once daily (original tablet) SEMA_PO_14MG_QD | -0.10 (-0.86 to 0.65) | -1.04 to 0.86 | -0.08 (-0.76 to 0.60) | Unclear |
| Semaglutide 7 mg oral once daily (original tablet) SEMA_PO_7MG_QD | -0.20 (-0.92 to 0.56) | -1.12 to 0.81 | -0.20 (-0.88 to 0.48) | Unclear |
| Orforglipron 3 mg oral once daily ORFO_PO_3MG_QD | -0.21 (-1.22 to 0.82) | -1.36 to 0.98 | -0.20 (-1.13 to 0.74) | Unclear |
| Orforglipron 36 mg oral once daily ORFO_PO_36MG_QD | -0.38 (-1.22 to 0.47) | -1.39 to 0.67 | -0.37 (-1.14 to 0.40) | Unclear |
| Semaglutide 3 mg oral once daily (original tablet) SEMA_PO_3MG_QD | -0.55 (-1.43 to 0.31) | -1.63 to 0.50 | -0.54 (-1.31 to 0.23) | 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 | SEMA_SC_0p5MG_QW | SEMA_SC_1p0MG_QW | EXENER_SC_2MG_QW | LIRA_SC_0p9MG_QD | INS_ASPART | DULA_SC_0p75MG_QW | ORFO_PO_12MG_QD | SITAGLIPTIN | SEMA_PO_14MG_QD | SEMA_PO_7MG_QD | ORFO_PO_3MG_QD | ORFO_PO_36MG_QD | SEMA_PO_3MG_QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | -1.30 -2.62 to 0.01 | -1.13 -2.17 to -0.11 | -0.68 -2.31 to 0.95 | -0.18 -1.52 to 1.13 | -0.17 -1.54 to 1.14 | -0.11 -1.83 to 1.65 | -0.08 -0.92 to 0.75 | 0.03 -0.92 to 0.97 | 0.10 -0.65 to 0.86 | 0.20 -0.56 to 0.92 | 0.21 -0.82 to 1.22 | 0.38 -0.47 to 1.22 | 0.55 -0.31 to 1.43 |
| SEMA_SC_0p5MG_QW | 1.30 -0.01 to 2.62 | SEMA_SC_0p5MG_QW | 0.17 -0.96 to 1.31 | 0.63 -1.04 to 2.30 | 1.12 -0.65 to 2.87 | 1.12 -0.29 to 2.55 | 1.20 -0.87 to 3.26 | 1.23 -0.24 to 2.67 | 1.33 0.19 to 2.48 | 1.41 0.06 to 2.78 | 1.50 0.14 to 2.83 | 1.52 -0.10 to 3.12 | 1.69 0.23 to 3.15 | 1.85 0.49 to 3.24 |
| SEMA_SC_1p0MG_QW | 1.13 0.11 to 2.17 | -0.17 -1.31 to 0.96 | SEMA_SC_1p0MG_QW | 0.45 -0.76 to 1.67 | 0.94 -0.66 to 2.54 | 0.94 0.09 to 1.78 | 1.03 -0.90 to 2.93 | 1.04 -0.19 to 2.25 | 1.15 0.18 to 2.13 | 1.23 0.12 to 2.38 | 1.32 0.20 to 2.44 | 1.35 -0.05 to 2.71 | 1.52 0.26 to 2.76 | 1.68 0.51 to 2.86 |
| EXENER_SC_2MG_QW | 0.68 -0.95 to 2.31 | -0.63 -2.30 to 1.04 | -0.45 -1.67 to 0.76 | EXENER_SC_2MG_QW | 0.48 -1.54 to 2.52 | 0.51 -1.01 to 1.97 | 0.59 -1.67 to 2.86 | 0.60 -1.14 to 2.34 | 0.71 -0.87 to 2.31 | 0.78 -0.93 to 2.45 | 0.88 -0.85 to 2.53 | 0.90 -1.01 to 2.74 | 1.06 -0.71 to 2.80 | 1.24 -0.49 to 2.94 |
| LIRA_SC_0p9MG_QD | 0.18 -1.13 to 1.52 | -1.12 -2.87 to 0.65 | -0.94 -2.54 to 0.66 | -0.48 -2.52 to 1.54 | LIRA_SC_0p9MG_QD | -0.00 -1.81 to 1.79 | 0.08 -1.95 to 2.08 | 0.11 -1.33 to 1.54 | 0.21 -1.22 to 1.66 | 0.28 -0.96 to 1.59 | 0.37 -0.90 to 1.66 | 0.39 -1.22 to 1.98 | 0.57 -0.84 to 2.02 | 0.75 -0.61 to 2.10 |
| INS_ASPART | 0.17 -1.14 to 1.54 | -1.12 -2.55 to 0.29 | -0.94 -1.78 to -0.09 | -0.51 -1.97 to 1.01 | 0.00 -1.79 to 1.81 | INS_ASPART | 0.09 -2.02 to 2.14 | 0.10 -1.40 to 1.57 | 0.22 -1.11 to 1.47 | 0.28 -1.13 to 1.70 | 0.39 -1.02 to 1.77 | 0.40 -1.25 to 1.96 | 0.57 -0.94 to 2.05 | 0.74 -0.75 to 2.18 |
| DULA_SC_0p75MG_QW | 0.11 -1.65 to 1.83 | -1.20 -3.26 to 0.87 | -1.03 -2.93 to 0.90 | -0.59 -2.86 to 1.67 | -0.08 -2.08 to 1.95 | -0.09 -2.14 to 2.02 | DULA_SC_0p75MG_QW | 0.03 -1.78 to 1.80 | 0.14 -1.63 to 1.89 | 0.21 -1.43 to 1.87 | 0.30 -1.34 to 1.94 | 0.32 -1.60 to 2.22 | 0.49 -1.30 to 2.24 | 0.66 -0.83 to 2.17 |
| ORFO_PO_12MG_QD | 0.08 -0.75 to 0.92 | -1.23 -2.67 to 0.24 | -1.04 -2.25 to 0.19 | -0.60 -2.34 to 1.14 | -0.11 -1.54 to 1.33 | -0.10 -1.57 to 1.40 | -0.03 -1.80 to 1.78 | ORFO_PO_12MG_QD | 0.10 -0.94 to 1.20 | 0.18 -0.63 to 1.02 | 0.27 -0.55 to 1.13 | 0.29 -0.79 to 1.34 | 0.45 -0.34 to 1.26 | 0.62 -0.33 to 1.63 |
| SITAGLIPTIN | -0.03 -0.97 to 0.92 | -1.33 -2.48 to -0.19 | -1.15 -2.13 to -0.18 | -0.71 -2.31 to 0.87 | -0.21 -1.66 to 1.22 | -0.22 -1.47 to 1.11 | -0.14 -1.89 to 1.63 | -0.10 -1.20 to 0.94 | SITAGLIPTIN | 0.06 -0.75 to 0.95 | 0.17 -0.67 to 1.00 | 0.18 -1.09 to 1.46 | 0.35 -0.71 to 1.42 | 0.52 -0.38 to 1.41 |
| SEMA_PO_14MG_QD | -0.10 -0.86 to 0.65 | -1.41 -2.78 to -0.06 | -1.23 -2.38 to -0.12 | -0.78 -2.45 to 0.93 | -0.28 -1.59 to 0.96 | -0.28 -1.70 to 1.13 | -0.21 -1.87 to 1.43 | -0.18 -1.02 to 0.63 | -0.06 -0.95 to 0.75 | SEMA_PO_14MG_QD | 0.09 -0.52 to 0.68 | 0.11 -1.03 to 1.25 | 0.28 -0.56 to 1.11 | 0.45 -0.30 to 1.19 |
| SEMA_PO_7MG_QD | -0.20 -0.92 to 0.56 | -1.50 -2.83 to -0.14 | -1.32 -2.44 to -0.20 | -0.88 -2.53 to 0.85 | -0.37 -1.66 to 0.90 | -0.39 -1.77 to 1.02 | -0.30 -1.94 to 1.34 | -0.27 -1.13 to 0.55 | -0.17 -1.00 to 0.67 | -0.09 -0.68 to 0.52 | SEMA_PO_7MG_QD | 0.02 -1.11 to 1.17 | 0.19 -0.64 to 1.01 | 0.36 -0.35 to 1.10 |
| ORFO_PO_3MG_QD | -0.21 -1.22 to 0.82 | -1.52 -3.12 to 0.10 | -1.35 -2.71 to 0.05 | -0.90 -2.74 to 1.01 | -0.39 -1.98 to 1.22 | -0.40 -1.96 to 1.25 | -0.32 -2.22 to 1.60 | -0.29 -1.34 to 0.79 | -0.18 -1.46 to 1.09 | -0.11 -1.25 to 1.03 | -0.02 -1.17 to 1.11 | ORFO_PO_3MG_QD | 0.17 -0.90 to 1.24 | 0.34 -0.89 to 1.58 |
| ORFO_PO_36MG_QD | -0.38 -1.22 to 0.47 | -1.69 -3.15 to -0.23 | -1.52 -2.76 to -0.26 | -1.06 -2.80 to 0.71 | -0.57 -2.02 to 0.84 | -0.57 -2.05 to 0.94 | -0.49 -2.24 to 1.30 | -0.45 -1.26 to 0.34 | -0.35 -1.42 to 0.71 | -0.28 -1.11 to 0.56 | -0.19 -1.01 to 0.64 | -0.17 -1.24 to 0.90 | ORFO_PO_36MG_QD | 0.17 -0.81 to 1.18 |
| SEMA_PO_3MG_QD | -0.55 -1.43 to 0.31 | -1.85 -3.24 to -0.49 | -1.68 -2.86 to -0.51 | -1.24 -2.94 to 0.49 | -0.75 -2.10 to 0.61 | -0.74 -2.18 to 0.75 | -0.66 -2.17 to 0.83 | -0.62 -1.63 to 0.33 | -0.52 -1.41 to 0.38 | -0.45 -1.19 to 0.30 | -0.36 -1.10 to 0.35 | -0.34 -1.58 to 0.89 | -0.17 -1.18 to 0.81 | SEMA_PO_3MG_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.
- NoteOutcome assessment, time point: selected time points span 26 to 56 weeks
- NoteOutcome assessment, analysis set: mixed: full_analysis 8, modified_itt 2, randomized 1
- NoteOutcome assessment, definition: mixed: not stated 10, SF-36v2 physical component summary change 1
- NoteOutcome assessment, instrument: mixed: not stated 9, SF-36v2 2
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 8, not stated 3
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 7, not stated 4
- NoteRisk of bias, blinding: mixed: double_blind 7, open_label 3, single_blind 1
| Trial | adjudicated | time weeks | analysis set | definition | instrument | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PIONEER 10 | not stated | 52 | full_analysis | not stated | SF-36v2 | 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 | not stated | 56 | full_analysis | SF-36v2 physical component summary change | SF-36v2 | 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 | not stated | 52 | full_analysis | 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 |
| ACHIEVE-3 | not stated | 52 | modified_itt | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2023 | adults T2D on metformin; HbA1c 7.0 to 10.5 percent |
| SUSTAIN 9 | not stated | 30 | full_analysis | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | adults 18 or older (20 in Japan); HbA1c 7.0 to 10.5 percent; stable SGLT2i with or without metformin or SU |
| PIONEER 12 | not stated | 26 | full_analysis | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2019 | adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent |
| ACHIEVE-5 | not stated | 40 | randomized | 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 |
| SUSTAIN | not stated | 30 | full_analysis | 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 |
| PIONEER 11 | not stated | 26 | full_analysis | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2019 | age 18 or older; HbA1c 7.0 to 10.0 percent at screening, 7.0 to 9.5 at randomization; no glucose lowering drugs; eGFR 60 or more |
| PIONEER 9 | not stated | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | Japanese adults 20 y or older; HbA1c 6.5 to 9.5 on one oral drug washed out, or 7.0 to 10.0 on diet and exercise |
| ACHIEVE-1 | not stated | 40 | modified_itt | 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 | A1 | SEMA_PO_3MG_QD | 52 | contrast, md | -0.670 | 0.709 | R0018421:Supplement Figure S5B | ||
| PIONEER 10 | A4 | DULA_SC_0p75MG_QW | 52 | contrast, md | R0018421:Supplement Figure S5B | ||||
| SUSTAIN™ 3 | A1 | SEMA_SC_1p0MG_QW | 56 | contrast, md | 0.460 | 0.561 | R0020680:Supplement Figure S5B | ||
| SUSTAIN™ 3 | A2 | EXENER_SC_2MG_QW | 56 | contrast, md | R0020680:Supplement Figure S5B | ||||
| SUSTAIN 11 | A1 | SEMA_SC_1p0MG_QW | 52 | contrast, md | 0.950 | 0.296 | R0022346:Results | ||
| SUSTAIN 11 | A2 | INS_ASPART | 52 | contrast, md | R0022346:Results | ||||
| ACHIEVE-3 | A1 | ORFO_PO_12MG_QD | 52 | arm, change | 2.880 | 0.333 | 329 | registry:outcomes | |
| ACHIEVE-3 | A2 | ORFO_PO_36MG_QD | 52 | arm, change | 2.570 | 0.328 | 320 | registry:outcomes | |
| ACHIEVE-3 | A3 | SEMA_PO_7MG_QD | 52 | arm, change | 2.890 | 0.322 | 324 | registry:outcomes | |
| ACHIEVE-3 | A4 | SEMA_PO_14MG_QD | 52 | arm, change | 2.560 | 0.324 | 353 | registry:outcomes | |
| SUSTAIN 9 | A1 | SEMA_SC_1p0MG_QW | 30 | arm, change | 1.900 | 0.399 | 151 | registry:outcomes | |
| SUSTAIN 9 | A2 | PLACEBO | 30 | arm, change | 0.700 | 0.439 | 151 | registry:outcomes | |
| PIONEER 12 | A1 | SEMA_PO_3MG_QD | 26 | arm, change | 0.150 | 0.296 | 322 | registry:outcomes | |
| PIONEER 12 | A2 | SEMA_PO_7MG_QD | 26 | arm, change | 0.290 | 0.265 | 320 | registry:outcomes | |
| PIONEER 12 | A3 | SEMA_PO_14MG_QD | 26 | arm, change | 0.980 | 0.289 | 299 | registry:outcomes | |
| PIONEER 12 | A4 | SITAGLIPTIN | 26 | arm, change | 0.690 | 0.308 | 334 | registry:outcomes | |
| ACHIEVE-5 | A1 | PLACEBO | 40 | arm, change | 0.710 | 0.491 | 141 | registry:outcomes | |
| ACHIEVE-5 | A2 | ORFO_PO_3MG_QD | 40 | arm, change | 0.470 | 0.496 | 137 | registry:outcomes | |
| ACHIEVE-5 | A3 | ORFO_PO_12MG_QD | 40 | arm, change | 1.070 | 0.592 | 132 | registry:outcomes | |
| ACHIEVE-5 | A4 | ORFO_PO_36MG_QD | 40 | arm, change | 0.350 | 0.572 | 136 | registry:outcomes | |
| SUSTAIN | A1 | SEMA_SC_0p5MG_QW | 30 | arm, change | 1.300 | 0.376 | 246 | registry:outcomes | |
| SUSTAIN | A2 | SEMA_SC_1p0MG_QW | 30 | arm, change | 1.100 | 0.380 | 249 | registry:outcomes | |
| SUSTAIN | A3 | SITAGLIPTIN | 30 | arm, change | 0.000 | 0.362 | 257 | registry:outcomes | |
| PIONEER 11 | A1 | SEMA_PO_3MG_QD | 26 | arm, change | 0.660 | 0.486 | 115 | registry:outcomes | |
| PIONEER 11 | A2 | SEMA_PO_7MG_QD | 26 | arm, change | 0.880 | 0.457 | 119 | registry:outcomes | |
| PIONEER 11 | A3 | SEMA_PO_14MG_QD | 26 | arm, change | 0.390 | 0.429 | 115 | registry:outcomes | |
| PIONEER 11 | A4 | PLACEBO | 26 | arm, change | 0.940 | 0.457 | 106 | registry:outcomes | |
| PIONEER 9 | A1 | SEMA_PO_3MG_QD | 52 | arm, change | -1.280 | 0.861 | 49 | registry:outcomes | |
| PIONEER 9 | A2 | SEMA_PO_7MG_QD | 52 | arm, change | -0.120 | 0.614 | 49 | registry:outcomes | |
| PIONEER 9 | A3 | SEMA_PO_14MG_QD | 52 | arm, change | 0.020 | 0.585 | 48 | registry:outcomes | |
| PIONEER 9 | A4 | LIRA_SC_0p9MG_QD | 52 | arm, change | 0.100 | 0.494 | 48 | registry:outcomes | |
| PIONEER 9 | A5 | PLACEBO | 52 | arm, change | -0.100 | 0.576 | 49 | registry:outcomes | |
| ACHIEVE-1 | A1 | PLACEBO | 40 | arm, change | 2.250 | 0.592 | 136 | registry:outcomes | |
| ACHIEVE-1 | A2 | ORFO_PO_3MG_QD | 40 | arm, change | 2.060 | 0.513 | 143 | registry:outcomes | |
| ACHIEVE-1 | A3 | ORFO_PO_12MG_QD | 40 | arm, change | 2.210 | 0.574 | 137 | registry:outcomes | |
| ACHIEVE-1 | A4 | ORFO_PO_36MG_QD | 40 | arm, change | 1.580 | 0.632 | 139 | 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.