Network meta-analysis
HbA1c change
Type 2 diabetes (adults); background therapy: one or more non insulin glucose lowering drugs
weeks 36 to 64 (target week 52)Not stated by the trialsDoses of a drug pooledMean difference
20
Randomized trials
19
Treatments
11,347
Participants
43
Trial arms
In plain language
Across 20 trials with 11,347 participants, 0 of 18 treatments had a clearly better result than placebo on HbA1c change, and for 18 the evidence could not tell them apart from placebo. The most favorable estimate was for Insulin icodec with semaglutide injection: mean difference -1.21 percentage points (95% credible interval -2.48 to 0.17).
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 percentage points. Lower values favor the treatment.
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Insulin icodec with semaglutide injection ICOSEMA_SC | -1.21 (-2.48 to 0.17) | -2.90 to 0.61 | -1.28 (-2.82 to 0.25) | Unclear |
| Tirzepatide injection TIRZ_SC | -0.91 (-2.46 to 0.75) | -2.83 to 1.07 | -0.92 (-2.95 to 1.10) | Unclear |
| Insulin degludec with liraglutide injection IDEGLIRA_SC | -0.82 (-2.04 to 0.48) | -2.46 to 0.88 | -0.85 (-2.31 to 0.61) | Unclear |
| Semaglutide injection SEMA_SC | -0.72 (-1.42 to 0.07) | -2.01 to 0.69 | -0.74 (-1.67 to 0.18) | Unclear |
| Cotadutide injection COTA_SC | -0.56 (-1.66 to 0.56) | -2.15 to 1.00 | -0.58 (-1.81 to 0.65) | Unclear |
| Liraglutide and empagliflozin injection EMPALIRA_SC | -0.49 (-1.70 to 0.83) | -2.16 to 1.32 | -0.53 (-2.03 to 0.97) | Unclear |
| Dulaglutide injection DULA_SC | -0.32 (-1.36 to 0.84) | -1.88 to 1.34 | -0.32 (-1.74 to 1.09) | Unclear |
| Taspoglutide injection TASP_SC | -0.25 (-1.37 to 0.95) | -1.88 to 1.44 | -0.24 (-1.74 to 1.26) | Unclear |
| Insulin degludec INS_DEGLUDEC | -0.24 (-1.42 to 1.04) | -1.85 to 1.48 | -0.23 (-1.69 to 1.23) | Unclear |
| Liraglutide injection LIRA_SC | -0.24 (-0.88 to 0.47) | -1.50 to 1.18 | -0.23 (-1.03 to 0.57) | Unclear |
| Canagliflozin CANAGLIFLOZIN | -0.22 (-1.47 to 1.15) | -1.94 to 1.62 | -0.25 (-1.79 to 1.28) | Unclear |
| Semaglutide tablet SEMA_PO | -0.22 (-1.49 to 1.26) | -1.96 to 1.66 | -0.19 (-1.86 to 1.47) | Unclear |
| Exenatide injection EXEN_SC | -0.06 (-1.29 to 1.18) | -1.68 to 1.63 | -0.03 (-1.68 to 1.63) | Unclear |
| Insulin glargine INS_GLARGINE | 0.05 (-1.13 to 1.31) | -1.65 to 1.74 | 0.05 (-1.57 to 1.68) | Unclear |
| Premixed insulin INS_PREMIX | 0.12 (-1.31 to 1.59) | -1.66 to 1.98 | 0.15 (-1.74 to 2.05) | Unclear |
| Basal insulin OTHER_ACTIVE_basal_insulin | 0.20 (-1.04 to 1.53) | -1.47 to 1.94 | 0.17 (-1.36 to 1.69) | Unclear |
| Empagliflozin EMPAGLIFLOZIN | 0.20 (-1.04 to 1.53) | -1.44 to 1.97 | 0.17 (-1.35 to 1.69) | Unclear |
| Sitagliptin SITAGLIPTIN | 0.21 (-0.64 to 1.15) | -1.24 to 1.72 | 0.22 (-0.90 to 1.35) | 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 | ICOSEMA_SC | TIRZ_SC | IDEGLIRA_SC | SEMA_SC | COTA_SC | EMPALIRA_SC | DULA_SC | TASP_SC | INS_DEGLUDEC | LIRA_SC | CANAGLIFLOZIN | SEMA_PO | EXEN_SC | INS_GLARGINE | INS_PREMIX | OTHER_ACTIVE_basal_insulin | EMPAGLIFLOZIN | SITAGLIPTIN |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 1.21 -0.17 to 2.48 | 0.91 -0.75 to 2.46 | 0.82 -0.48 to 2.04 | 0.72 -0.07 to 1.42 | 0.56 -0.56 to 1.66 | 0.49 -0.83 to 1.70 | 0.32 -0.84 to 1.36 | 0.25 -0.95 to 1.37 | 0.24 -1.04 to 1.42 | 0.24 -0.47 to 0.88 | 0.22 -1.15 to 1.47 | 0.22 -1.26 to 1.49 | 0.06 -1.18 to 1.29 | -0.05 -1.31 to 1.13 | -0.12 -1.59 to 1.31 | -0.20 -1.53 to 1.04 | -0.20 -1.53 to 1.04 | -0.21 -1.15 to 0.64 |
| ICOSEMA_SC | -1.21 -2.48 to 0.17 | ICOSEMA_SC | -0.31 -2.21 to 1.60 | -0.38 -2.14 to 1.34 | -0.50 -1.59 to 0.64 | -0.64 -2.31 to 1.11 | -0.71 -2.44 to 0.97 | -0.90 -2.35 to 0.63 | -0.94 -2.55 to 0.72 | -0.97 -2.72 to 0.68 | -0.96 -2.30 to 0.38 | -0.98 -2.58 to 0.64 | -1.00 -2.75 to 0.79 | -1.16 -2.72 to 0.51 | -1.25 -2.83 to 0.36 | -1.35 -3.07 to 0.59 | -1.40 -3.15 to 0.35 | -1.39 -3.17 to 0.34 | -1.42 -2.79 to -0.00 |
| TIRZ_SC | -0.91 -2.46 to 0.75 | 0.31 -1.60 to 2.21 | TIRZ_SC | -0.07 -1.98 to 1.84 | -0.17 -1.74 to 1.40 | -0.34 -2.24 to 1.64 | -0.41 -2.40 to 1.60 | -0.58 -2.00 to 0.89 | -0.64 -2.29 to 0.98 | -0.68 -2.61 to 1.26 | -0.66 -2.30 to 1.00 | -0.67 -2.62 to 1.24 | -0.68 -2.65 to 1.25 | -0.86 -2.33 to 0.69 | -0.95 -2.01 to 0.18 | -1.03 -2.71 to 0.74 | -1.09 -3.10 to 0.90 | -1.09 -3.11 to 0.91 | -1.10 -2.77 to 0.54 |
| IDEGLIRA_SC | -0.82 -2.04 to 0.48 | 0.38 -1.34 to 2.14 | 0.07 -1.84 to 1.98 | IDEGLIRA_SC | -0.11 -1.37 to 1.22 | -0.25 -1.90 to 1.43 | -0.34 -1.88 to 1.22 | -0.52 -2.02 to 1.03 | -0.58 -2.11 to 1.04 | -0.60 -1.73 to 0.54 | -0.59 -1.68 to 0.49 | -0.62 -2.26 to 1.16 | -0.61 -2.34 to 1.08 | -0.78 -2.36 to 0.89 | -0.88 -2.49 to 0.80 | -0.96 -2.70 to 0.92 | -1.03 -2.67 to 0.58 | -1.02 -2.61 to 0.54 | -1.03 -2.39 to 0.33 |
| SEMA_SC | -0.72 -1.42 to 0.07 | 0.50 -0.64 to 1.59 | 0.17 -1.40 to 1.74 | 0.11 -1.22 to 1.37 | SEMA_SC | -0.15 -1.49 to 1.19 | -0.22 -1.56 to 1.04 | -0.41 -1.35 to 0.55 | -0.46 -1.60 to 0.67 | -0.49 -1.81 to 0.76 | -0.48 -1.23 to 0.26 | -0.49 -1.61 to 0.63 | -0.52 -1.86 to 0.82 | -0.67 -1.84 to 0.60 | -0.77 -1.92 to 0.40 | -0.85 -2.27 to 0.63 | -0.91 -2.26 to 0.42 | -0.92 -2.28 to 0.43 | -0.92 -1.72 to -0.11 |
| COTA_SC | -0.56 -1.66 to 0.56 | 0.64 -1.11 to 2.31 | 0.34 -1.64 to 2.24 | 0.25 -1.43 to 1.90 | 0.15 -1.19 to 1.49 | COTA_SC | -0.06 -1.75 to 1.53 | -0.25 -1.81 to 1.36 | -0.31 -1.88 to 1.29 | -0.34 -1.96 to 1.27 | -0.33 -1.66 to 0.94 | -0.35 -2.06 to 1.34 | -0.33 -2.20 to 1.34 | -0.51 -2.12 to 1.17 | -0.61 -2.30 to 1.03 | -0.68 -2.50 to 1.11 | -0.75 -2.45 to 0.89 | -0.75 -2.48 to 0.92 | -0.78 -2.22 to 0.66 |
| EMPALIRA_SC | -0.49 -1.70 to 0.83 | 0.71 -0.97 to 2.44 | 0.41 -1.60 to 2.40 | 0.34 -1.22 to 1.88 | 0.22 -1.04 to 1.56 | 0.06 -1.53 to 1.75 | EMPALIRA_SC | -0.18 -1.71 to 1.45 | -0.22 -1.83 to 1.41 | -0.27 -1.80 to 1.29 | -0.25 -1.39 to 0.89 | -0.26 -1.98 to 1.46 | -0.28 -2.02 to 1.49 | -0.44 -2.05 to 1.29 | -0.54 -2.19 to 1.19 | -0.62 -2.39 to 1.27 | -0.69 -1.86 to 0.52 | -0.69 -1.88 to 0.53 | -0.70 -2.08 to 0.71 |
| DULA_SC | -0.32 -1.36 to 0.84 | 0.90 -0.63 to 2.35 | 0.58 -0.89 to 2.00 | 0.52 -1.03 to 2.02 | 0.41 -0.55 to 1.35 | 0.25 -1.36 to 1.81 | 0.18 -1.45 to 1.71 | DULA_SC | -0.06 -1.34 to 1.25 | -0.08 -1.63 to 1.43 | -0.07 -1.23 to 1.04 | -0.10 -1.59 to 1.32 | -0.11 -1.73 to 1.45 | -0.27 -1.49 to 1.03 | -0.36 -1.36 to 0.63 | -0.44 -1.89 to 1.06 | -0.51 -2.16 to 1.06 | -0.50 -2.16 to 1.05 | -0.53 -1.71 to 0.64 |
| TASP_SC | -0.25 -1.37 to 0.95 | 0.94 -0.72 to 2.55 | 0.64 -0.98 to 2.29 | 0.58 -1.04 to 2.11 | 0.46 -0.67 to 1.60 | 0.31 -1.29 to 1.88 | 0.22 -1.41 to 1.83 | 0.06 -1.25 to 1.34 | TASP_SC | -0.02 -1.61 to 1.52 | -0.01 -1.20 to 1.10 | -0.04 -1.62 to 1.55 | -0.05 -1.56 to 1.38 | -0.20 -1.19 to 0.84 | -0.31 -1.59 to 0.99 | -0.38 -1.68 to 0.98 | -0.45 -2.06 to 1.17 | -0.45 -2.16 to 1.21 | -0.46 -1.48 to 0.52 |
| INS_DEGLUDEC | -0.24 -1.42 to 1.04 | 0.97 -0.68 to 2.72 | 0.68 -1.26 to 2.61 | 0.60 -0.54 to 1.73 | 0.49 -0.76 to 1.81 | 0.34 -1.27 to 1.96 | 0.27 -1.29 to 1.80 | 0.08 -1.43 to 1.63 | 0.02 -1.52 to 1.61 | INS_DEGLUDEC | 0.00 -1.07 to 1.11 | -0.02 -1.70 to 1.75 | -0.02 -1.71 to 1.71 | -0.18 -1.75 to 1.45 | -0.28 -1.90 to 1.40 | -0.36 -2.07 to 1.52 | -0.44 -1.98 to 1.21 | -0.42 -2.00 to 1.18 | -0.43 -1.77 to 0.92 |
| LIRA_SC | -0.24 -0.88 to 0.47 | 0.96 -0.38 to 2.30 | 0.66 -1.00 to 2.30 | 0.59 -0.49 to 1.68 | 0.48 -0.26 to 1.23 | 0.33 -0.94 to 1.66 | 0.25 -0.89 to 1.39 | 0.07 -1.04 to 1.23 | 0.01 -1.10 to 1.20 | -0.00 -1.11 to 1.07 | LIRA_SC | -0.03 -1.34 to 1.31 | -0.02 -1.41 to 1.32 | -0.19 -1.39 to 1.09 | -0.30 -1.53 to 0.99 | -0.36 -1.79 to 1.18 | -0.44 -1.61 to 0.73 | -0.43 -1.61 to 0.71 | -0.45 -1.27 to 0.39 |
| CANAGLIFLOZIN | -0.22 -1.47 to 1.15 | 0.98 -0.64 to 2.58 | 0.67 -1.24 to 2.62 | 0.62 -1.16 to 2.26 | 0.49 -0.63 to 1.61 | 0.35 -1.34 to 2.06 | 0.26 -1.46 to 1.98 | 0.10 -1.32 to 1.59 | 0.04 -1.55 to 1.62 | 0.02 -1.75 to 1.70 | 0.03 -1.31 to 1.34 | CANAGLIFLOZIN | -0.01 -1.78 to 1.73 | -0.17 -1.78 to 1.51 | -0.27 -1.88 to 1.37 | -0.34 -2.14 to 1.50 | -0.41 -2.20 to 1.36 | -0.41 -2.18 to 1.27 | -0.42 -1.82 to 0.95 |
| SEMA_PO | -0.22 -1.49 to 1.26 | 1.00 -0.79 to 2.75 | 0.68 -1.25 to 2.65 | 0.61 -1.08 to 2.34 | 0.52 -0.82 to 1.86 | 0.33 -1.34 to 2.20 | 0.28 -1.49 to 2.02 | 0.11 -1.45 to 1.73 | 0.05 -1.38 to 1.56 | 0.02 -1.71 to 1.71 | 0.02 -1.32 to 1.41 | 0.01 -1.73 to 1.78 | SEMA_PO | -0.16 -1.74 to 1.47 | -0.26 -1.87 to 1.41 | -0.33 -2.07 to 1.50 | -0.41 -2.21 to 1.41 | -0.40 -2.22 to 1.37 | -0.42 -1.49 to 0.68 |
| EXEN_SC | -0.06 -1.29 to 1.18 | 1.16 -0.51 to 2.72 | 0.86 -0.69 to 2.33 | 0.78 -0.89 to 2.36 | 0.67 -0.60 to 1.84 | 0.51 -1.17 to 2.12 | 0.44 -1.29 to 2.05 | 0.27 -1.03 to 1.49 | 0.20 -0.84 to 1.19 | 0.18 -1.45 to 1.75 | 0.19 -1.09 to 1.39 | 0.17 -1.51 to 1.78 | 0.16 -1.47 to 1.74 | EXEN_SC | -0.10 -1.19 to 0.93 | -0.18 -1.04 to 0.72 | -0.24 -2.02 to 1.39 | -0.24 -2.06 to 1.42 | -0.25 -1.49 to 0.89 |
| INS_GLARGINE | 0.05 -1.13 to 1.31 | 1.25 -0.36 to 2.83 | 0.95 -0.18 to 2.01 | 0.88 -0.80 to 2.49 | 0.77 -0.40 to 1.92 | 0.61 -1.03 to 2.30 | 0.54 -1.19 to 2.19 | 0.36 -0.63 to 1.36 | 0.31 -0.99 to 1.59 | 0.28 -1.40 to 1.90 | 0.30 -0.99 to 1.53 | 0.27 -1.37 to 1.88 | 0.26 -1.41 to 1.87 | 0.10 -0.93 to 1.19 | INS_GLARGINE | -0.08 -1.40 to 1.31 | -0.15 -1.88 to 1.53 | -0.13 -1.90 to 1.56 | -0.16 -1.44 to 1.07 |
| INS_PREMIX | 0.12 -1.31 to 1.59 | 1.35 -0.59 to 3.07 | 1.03 -0.74 to 2.71 | 0.96 -0.92 to 2.70 | 0.85 -0.63 to 2.27 | 0.68 -1.11 to 2.50 | 0.62 -1.27 to 2.39 | 0.44 -1.06 to 1.89 | 0.38 -0.98 to 1.68 | 0.36 -1.52 to 2.07 | 0.36 -1.18 to 1.79 | 0.34 -1.50 to 2.14 | 0.33 -1.50 to 2.07 | 0.18 -0.72 to 1.04 | 0.08 -1.31 to 1.40 | INS_PREMIX | -0.06 -2.05 to 1.74 | -0.07 -2.05 to 1.77 | -0.08 -1.54 to 1.29 |
| OTHER_ACTIVE_basal_insulin | 0.20 -1.04 to 1.53 | 1.40 -0.35 to 3.15 | 1.09 -0.90 to 3.10 | 1.03 -0.58 to 2.67 | 0.91 -0.42 to 2.26 | 0.75 -0.89 to 2.45 | 0.69 -0.52 to 1.86 | 0.51 -1.06 to 2.16 | 0.45 -1.17 to 2.06 | 0.44 -1.21 to 1.98 | 0.44 -0.73 to 1.61 | 0.41 -1.36 to 2.20 | 0.41 -1.41 to 2.21 | 0.24 -1.39 to 2.02 | 0.15 -1.53 to 1.88 | 0.06 -1.74 to 2.05 | OTHER_ACTIVE_basal_insulin | -0.00 -1.25 to 1.25 | -0.02 -1.42 to 1.42 |
| EMPAGLIFLOZIN | 0.20 -1.04 to 1.53 | 1.39 -0.34 to 3.17 | 1.09 -0.91 to 3.11 | 1.02 -0.54 to 2.61 | 0.92 -0.43 to 2.28 | 0.75 -0.92 to 2.48 | 0.69 -0.53 to 1.88 | 0.50 -1.05 to 2.16 | 0.45 -1.21 to 2.16 | 0.42 -1.18 to 2.00 | 0.43 -0.71 to 1.61 | 0.41 -1.27 to 2.18 | 0.40 -1.37 to 2.22 | 0.24 -1.42 to 2.06 | 0.13 -1.56 to 1.90 | 0.07 -1.77 to 2.05 | 0.00 -1.25 to 1.25 | EMPAGLIFLOZIN | -0.03 -1.40 to 1.47 |
| SITAGLIPTIN | 0.21 -0.64 to 1.15 | 1.42 0.00 to 2.79 | 1.10 -0.54 to 2.77 | 1.03 -0.33 to 2.39 | 0.92 0.11 to 1.72 | 0.78 -0.66 to 2.22 | 0.70 -0.71 to 2.08 | 0.53 -0.64 to 1.71 | 0.46 -0.52 to 1.48 | 0.43 -0.92 to 1.77 | 0.45 -0.39 to 1.27 | 0.42 -0.95 to 1.82 | 0.42 -0.68 to 1.49 | 0.25 -0.89 to 1.49 | 0.16 -1.07 to 1.44 | 0.08 -1.29 to 1.54 | 0.02 -1.42 to 1.42 | 0.03 -1.47 to 1.40 | SITAGLIPTIN |
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 | Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 20 of 20 | Baseline HbA1c (percent) effect modifier, prognostic factor; 19 of 20 | Diabetes duration (years) effect modifier, prognostic factor; 17 of 20 | Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 14 of 20 | Age (years) prognostic factor; 20 of 20 | Treatment duration (weeks) effect modifier; 20 of 20 |
|---|---|---|---|---|---|---|
| SUSTAIN™ 2 S001876 | S1 | 8.07 | 6.6 | 25.1 | 55.13 | 56 |
| NCT00754988 S000027 | S1 | 7.96 | 5.87 | 8.82 | 55.91 | 156 |
| COMBINE 2 S000155 | S1 | 8 | 12.64 | 27.65 | 59.1 | 52 |
| NCT03235050 S000257 | S1 | not reported | not reported | 0.72 | 56.79 | 54 |
| SUSTAIN 7 S000372 | S1 | 8.23 | 7.4 | 15.9 | 55.5 | 40 |
| NCT00717457 S000414 | S1 | 8.1 | 6.6 | not reported | 55.67 | 52 |
| NCT00082407 S000441 | S1 | 8.6 | 9.9 | not reported | 58.5 | 52 |
| NCT03878706 S000665 | S1 | 8.05 | 6.5 median | not reported | 57.5 | 52.14 |
| NCT00395746 S000862 | S1 | 8.82 | 10.33 | 100 region: all sites in Asia | 59.67 | 52 |
| NCT00097500 S001020 | S1 | 7.5 | 4.89 | not reported | 58.35 | 52 |
| PIONEER 7 S001153 | S1 | 7.93 | 8.71 | 15.08 | 57.64 | 104 |
| SURPASS-4 S001287 | S1 | 8.52 | 11.8 | 3.5 | 63.62 | 104 |
| AWARD-CHN2 S001404 | S1 | 8.37 | 8.13 | 81.52 | 54.97 | 52 |
| NCT05486065 S001555 | S1 | 8.35 | 6.96 | 1.49 | 52.76 | 40 |
| SUSTAIN 8 S001847 | S1 | 8.25 | not reported | 15.86 | 56.6 | 52 |
| DUAL™ I Japan S001965 | S1 | 8.43 | 9.43 | 100 region: all sites in Asia | 57.16 | 52 |
| NCT00700817 S002361 | S1 | 8.43 | 6.23 | 1.65 | 55.3 | 26 |
| S002969 S002969 | S1 | 6.74 median | 3.48 median | not reported | 52.3 | 26 |
| S003030 S003030 | S1 | 8.5 | 7.2 | 100 region: all sites in Asia | 58.44 | 52 |
| S003432 S003432 | S1 | 8.35 | not reported | not reported | 51.05 | 52 |
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 HbA1c: design means range from 7.5 (EXEN_SC vs INS_GLARGINE) to 8.5 (EXEN_SC vs INS_PREMIX) percent; threshold 0.5
- FlagBaseline, Diabetes duration: design means range from 4.9 (EXEN_SC vs INS_GLARGINE) to 12.6 (ICOSEMA_SC vs SEMA_SC) years; threshold 3
- FlagBaseline, Asian ancestry or region: not reported by 6 of 20 trials
- FlagBaseline, Asian ancestry or region: design means range from 0.7 (COTA_SC vs PLACEBO) to 100.0 (EXEN_SC vs INS_PREMIX) percent Asian; threshold 30
- FlagBaseline, Age: design means range from 51.0 (LIRA_SC vs SEMA_SC) to 63.6 (INS_GLARGINE vs TIRZ_SC) years; threshold 10
- FlagBaseline, Treatment duration: design means range from 26.0 (LIRA_SC vs SITAGLIPTIN) to 156.0 (SITAGLIPTIN vs TASP_SC) weeks; threshold 26
- FlagHeterogeneity, tau above threshold: tau 0.52 exceeds the outcome threshold 0.3; the flags of this network are candidate explanations
- NoteOutcome assessment, time point: selected time points span 40 to 56 weeks
- NoteOutcome assessment, analysis set: mixed: completers 1, full_analysis 9, modified_itt 6, other 3, randomized 1
- NoteOutcome assessment, definition: mixed: mean HbA1c change baseline to week 52 1, not stated 18, Observed HbA1c at 12 months, mean and SD 1
- NoteRisk of bias, blinding: mixed: double_blind 7, open_label 12, single_blind 1
- NoteRisk of bias, funding: mixed: industry 18, non_industry 2
- NoteData handling, input conversions: arms_combined 13, median_converted 2
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | funding | intercurrent events (rescue) | blinding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SUSTAIN™ 2 | 56 | full_analysis | not stated | not stated | not stated | not stated | not stated | industry | not stated | double_blind | 2013 | type 2 diabetes on metformin and or thiazolidinedione; HbA1c 7.0 to 10.5 percent |
| NCT00754988 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | industry | not stated | double_blind | 2008 | age 18 to 75; HbA1c 7.0 to 10.0 percent; BMI 25 (23 Asian) to 45; metformin at least 1500 mg |
| COMBINE 2 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2022 | adults T2D on GLP-1 RA with or without oral drugs; HbA1c 7.0 to 10.0 percent |
| NCT03235050 | 54 | full_analysis | not stated | not stated | not stated | not stated | not stated | industry | not stated | double_blind | 2017 | age 18 or older; BMI 25 or higher; HbA1c 7.0 to 10.5 percent; on metformin |
| SUSTAIN 7 | 40 | full_analysis | not stated | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2016 | age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin background |
| NCT00717457 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2008 | age 18 to 75; HbA1c 7 to 10 percent; BMI 25 to 45 (above 23 for Asians); metformin with or without TZD |
| NCT00082407 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2003 | Age 30 to 75; HbA1c 7.0 to 11.0 on metformin plus sulfonylurea; BMI 25 to 40 |
| NCT03878706 | 52.14 | completers | Observed HbA1c at 12 months, mean and SD | not stated | not stated | not stated | not stated | non_industry | not stated | single_blind | 2017 | T2D on metformin, HbA1c above 7 percent, high or very high CV risk, eGFR 60 or more |
| NCT00395746 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | industry | not stated | double_blind | 2006 | age 20 or older; HbA1c 7.4 to 10.4 on one sulfonylurea |
| NCT00097500 | 52 | other | not stated | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2004 | age 30 to 75; HbA1c 6.5 to 9.5 percent; BMI 25 to 40; on metformin |
| PIONEER 7 | 52 | randomized | not stated | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2016 | age 18 or more; HbA1c 7.5 to 9.5 percent; one or two oral glucose lowering drugs |
| SURPASS-4 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2018 | age 18 or older; HbA1c 7.5 to 10.5 percent; BMI 25 or more; increased cardiovascular risk; 1 to 3 oral agents |
| AWARD-CHN2 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2012 | age 18 or older; BMI 19 to 35 kg/m2; HbA1c 7.0 to 11.0 percent on metformin and/or sulfonylurea |
| NCT05486065 | 40 | full_analysis | not stated | not stated | not stated | not stated | not stated | industry | not stated | double_blind | 2022 | age 18 to 64; HbA1c 7.0 to 10.5; BMI 27 or more; on metformin |
| SUSTAIN 8 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | industry | not stated | double_blind | 2017 | age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin 1500 mg or maximum tolerated |
| DUAL™ I Japan | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2015 | Japanese adults 20 or older; HbA1c 7.0 to 11.0 percent; BMI at least 20; insulin naive on one oral drug |
| NCT00700817 | 52 | other | not stated | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2008 | age 18 to 80; HbA1c 7.5 to 10%; BMI 45 or less; metformin 1500 mg/day or more for 3 months |
| S002969 | 52.14 | modified_itt | not stated | not stated | not stated | not stated | not stated | industry | not stated | double_blind | 2018 | age 18 to 70; BMI 30 to 50; HbA1c 48 to below 97 mmol/mol; T2DM under 10 years; undergoing LAGB |
| S003030 | 52 | full_analysis | mean HbA1c change baseline to week 52 | not stated | not stated | not stated | not stated | industry | not stated | open_label | 2015 | age 20 to 75; HbA1c 7.5 to 11 percent; two or more oral agents for 3 months |
| S003432 | 52 | other | not stated | not stated | not stated | not stated | not stated | non_industry | not stated | open_label | 2020 | age 18 to 65; type 2 diabetes 1 year or more; HbA1c 7.0 to 10.5 percent; BMI 30 or higher; stable 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 |
|---|---|---|---|---|---|---|---|---|---|
| NCT00754988 | A2+A3 | TASP_SC | 52 | arm, change | -1.106 | 0.043 | 369 | arms_combined | R0022521:Results |
| NCT00754988 | A4 | SITAGLIPTIN | 52 | arm, change | -0.660 | 0.061 | 177 | R0022521:Results | |
| COMBINE 2 | A1 | ICOSEMA_SC | 52 | arm, change | -1.400 | 0.050 | 325 | registry:outcomes | |
| COMBINE 2 | A2 | SEMA_SC | 52 | arm, change | -0.860 | 0.052 | 335 | registry:outcomes | |
| NCT03235050 | A1 | PLACEBO | 54 | arm, change | -0.440 | 0.099 | 112 | registry:outcomes | |
| NCT03235050 | A3+A4+A5 | COTA_SC | 54 | arm, change | -1.023 | 0.043 | 612 | arms_combined | registry:outcomes |
| SUSTAIN 7 | A1+A2 | SEMA_SC | 40 | arm, change | -1.645 | 0.043 | 601 | arms_combined | registry:outcomes |
| SUSTAIN 7 | A3+A4 | DULA_SC | 40 | arm, change | -1.240 | 0.039 | 598 | arms_combined | registry:outcomes |
| NCT00717457 | A1+A2 | TASP_SC | 52 | arm, change | -1.170 | 0.064 | 776 | arms_combined | R0013639:Results |
| NCT00717457 | A3 | EXEN_SC | 52 | arm, change | -0.940 | 0.090 | 373 | R0013639:Results | |
| NCT00082407 | A1 | EXEN_SC | 52 | arm, change | -1.040 | 0.070 | 253 | R0025791:Table 2 | |
| NCT00082407 | A2 | INS_PREMIX | 52 | arm, change | -0.890 | 0.060 | 248 | R0025791:Table 2 | |
| NCT03878706 | A1 | OTHER_ACTIVE_basal_insulin | 52.14 | arm, final | 7.100 | 0.190 | 40 | R0008057:Table 2 | |
| NCT03878706 | A2 | LIRA_SC | 52.14 | arm, final | 6.700 | 0.142 | 40 | R0008057:Table 2 | |
| NCT03878706 | A3 | EMPAGLIFLOZIN | 52.14 | arm, final | 7.100 | 0.174 | 40 | R0008057:Table 2 | |
| NCT03878706 | A4 | EMPALIRA_SC | 52.14 | arm, final | 6.400 | 0.126 | 40 | R0008057:Table 2 | |
| NCT00395746 | A1+A2 | LIRA_SC | 52 | arm, final | 7.649 | 0.071 | 173 | arms_combined | R0022802:Table 2 |
| NCT00395746 | A3 | PLACEBO | 52 | arm, final | 8.800 | 0.100 | 88 | R0022802:Table 2 | |
| NCT00097500 | A1 | EXEN_SC | 52 | arm, change | -0.800 | 0.100 | R0027264:Results | ||
| NCT00097500 | A2 | INS_GLARGINE | 52 | arm, change | -0.700 | 0.200 | R0027264:Results | ||
| PIONEER 7 | A1+A3 | SEMA_PO | 52 | arm, change | -0.986 | 0.062 | 322 | arms_combined | registry:outcomes |
| PIONEER 7 | A2+A4 | SITAGLIPTIN | 52 | arm, change | -0.570 | 0.058 | 334 | arms_combined | registry:outcomes |
| SURPASS-4 | A1+A2+A3 | TIRZ_SC | 52 | arm, change | -2.418 | 0.031 | 863 | arms_combined | registry:outcomes |
| SURPASS-4 | A4 | INS_GLARGINE | 52 | arm, change | -1.440 | 0.030 | 887 | registry:outcomes | |
| AWARD-CHN2 | A1+A2 | DULA_SC | 52 | arm, change | -1.250 | 0.055 | 505 | arms_combined | R0023722:Results |
| AWARD-CHN2 | A3 | INS_GLARGINE | 52 | arm, change | -0.890 | 0.075 | 250 | R0023722:Results | |
| NCT05486065 | A1+A2+A3 | SEMA_SC | 40 | arm, change | -1.933 | 0.106 | 169 | arms_combined | registry:outcomes |
| NCT05486065 | A4 | PLACEBO | 40 | arm, change | -1.100 | 0.177 | 54 | registry:outcomes | |
| SUSTAIN 8 | A1 | SEMA_SC | 52 | contrast, md | -0.490 | 0.082 | registry:outcomes | ||
| SUSTAIN 8 | A2 | CANAGLIFLOZIN | 52 | contrast, md | registry:outcomes | ||||
| SUSTAIN™ 2 | A1+A2 | SEMA_SC | 56 | arm, change | -1.465 | 0.036 | 818 | arms_combined | registry:outcomes |
| SUSTAIN™ 2 | A3 | SITAGLIPTIN | 56 | arm, change | -0.550 | 0.050 | 407 | registry:outcomes | |
| DUAL™ I Japan | A1 | IDEGLIRA_SC | 52 | arm, change | -2.420 | 0.063 | 275 | registry:outcomes | |
| DUAL™ I Japan | A2 | INS_DEGLUDEC | 52 | arm, change | -1.800 | 0.062 | 271 | registry:outcomes | |
| DUAL™ I Japan | A3 | LIRA_SC | 52 | arm, change | -1.800 | 0.056 | 273 | registry:outcomes | |
| NCT00700817 | A1+A2 | LIRA_SC | 52 | arm, change | -1.401 | 0.051 | 425 | arms_combined | R0024199:Results |
| NCT00700817 | A3 | SITAGLIPTIN | 52 | arm, change | -0.880 | 0.071 | 210 | R0024199:Results | |
| S002969 | A1 | LIRA_SC | 52.14 | arm, change | 0.747 | 0.068 | 12 | median_converted | R0010852:Table 2 |
| S002969 | A2 | PLACEBO | 52.14 | arm, change | -0.320 | 0.357 | 13 | median_converted | R0010852:Table 2 |
| S003030 | A1 | EXEN_SC | 52 | arm, change | -1.310 | 0.273 | 27 | R0018574:Table 2 | |
| S003030 | A2 | INS_PREMIX | 52 | arm, change | -1.090 | 0.251 | 32 | R0018574:Table 2 | |
| S003432 | A1 | SEMA_SC | 52 | contrast, md | -0.500 | 0.107 | R0053844:p4 | ||
| S003432 | A2 | LIRA_SC | 52 | contrast, md | R0053844:p4 |
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.