Network meta-analysis
HbA1c change
Type 2 diabetes (adults); background therapy: one or more non insulin glucose lowering drugs
weeks 20 to 36 (target week 26)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean difference
19
Randomized trials
20
Treatments
11,980
Participants
56
Trial arms
In plain language
Across 19 trials with 11,980 participants, 19 of 19 treatments had a clearly better result than placebo on HbA1c change. The most favorable estimate was for Tirzepatide 15 mg subcutaneous once weekly: mean difference -1.86 percentage points (95% credible interval -2.20 to -1.52).
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 |
|---|---|---|---|---|
| Tirzepatide 15 mg subcutaneous once weekly TIRZ_SC_15MG_QW | -1.86 (-2.20 to -1.52) | -2.31 to -1.39 | -1.89 (-2.23 to -1.55) | Better |
| Tirzepatide 10 mg subcutaneous once weekly TIRZ_SC_10MG_QW | -1.78 (-2.11 to -1.45) | -2.23 to -1.31 | -1.81 (-2.14 to -1.47) | Better |
| Tirzepatide 5 mg subcutaneous once weekly TIRZ_SC_5MG_QW | -1.58 (-1.91 to -1.25) | -2.03 to -1.12 | -1.61 (-1.94 to -1.27) | Better |
| Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW | -1.33 (-1.62 to -1.05) | -1.75 to -0.91 | -1.35 (-1.62 to -1.07) | Better |
| Semaglutide 14 mg oral once daily (original tablet) SEMA_PO_14MG_QD | -1.25 (-1.48 to -1.00) | -1.64 to -0.85 | -1.26 (-1.49 to -1.03) | Better |
| Dulaglutide 1.5 mg subcutaneous once weekly DULA_SC_1p5MG_QW | -1.08 (-1.27 to -0.89) | -1.45 to -0.72 | -1.10 (-1.28 to -0.91) | Better |
| Liraglutide 1.8 mg subcutaneous once daily LIRA_SC_1p8MG_QD | -1.07 (-1.34 to -0.79) | -1.49 to -0.65 | -1.08 (-1.36 to -0.81) | Better |
| IGlarLixi 2:1 pen subcutaneous once daily titrated IGLARLIXI2_SC_TIT_QD | -1.05 (-1.38 to -0.72) | -1.52 to -0.60 | -1.07 (-1.40 to -0.74) | Better |
| Insulin degludec INS_DEGLUDEC | -1.00 (-1.40 to -0.58) | -1.51 to -0.48 | -1.03 (-1.44 to -0.62) | Better |
| Semaglutide 0.5 mg subcutaneous once weekly SEMA_SC_0p5MG_QW | -0.99 (-1.37 to -0.61) | -1.47 to -0.50 | -1.01 (-1.38 to -0.64) | Better |
| Semaglutide 7 mg oral once daily (original tablet) SEMA_PO_7MG_QD | -0.98 (-1.24 to -0.69) | -1.39 to -0.57 | -0.99 (-1.25 to -0.73) | Better |
| Tirzepatide 1 mg subcutaneous once weekly TIRZ_SC_1MG_QW | -0.95 (-1.34 to -0.55) | -1.44 to -0.45 | -0.97 (-1.38 to -0.57) | Better |
| Dulaglutide 0.75 mg subcutaneous once weekly DULA_SC_0p75MG_QW | -0.90 (-1.09 to -0.70) | -1.28 to -0.51 | -0.91 (-1.10 to -0.72) | Better |
| Insulin glargine INS_GLARGINE | -0.61 (-0.87 to -0.35) | -1.02 to -0.19 | -0.62 (-0.88 to -0.37) | Better |
| Visepegenatide 150 µg injection once weekly VISEPE_SC_150UG_QW | -0.57 (-0.92 to -0.22) | -1.04 to -0.11 | -0.57 (-0.91 to -0.23) | Better |
| Exenatide 10 ug subcutaneous twice daily EXEN_SC_10UG_BID | -0.56 (-0.87 to -0.25) | -0.99 to -0.11 | -0.57 (-0.88 to -0.26) | Better |
| Sitagliptin SITAGLIPTIN | -0.47 (-0.70 to -0.22) | -0.85 to -0.07 | -0.48 (-0.71 to -0.25) | Better |
| Semaglutide 3 mg oral once daily (original tablet) SEMA_PO_3MG_QD | -0.41 (-0.68 to -0.15) | -0.83 to 0.02 | -0.43 (-0.69 to -0.16) | Better |
| Lixisenatide 20 ug subcutaneous once daily LIXI_SC_20UG_QD | -0.29 (-0.55 to -0.03) | -0.69 to 0.13 | -0.30 (-0.56 to -0.04) | Better |
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 | TIRZ_SC_15MG_QW | TIRZ_SC_10MG_QW | TIRZ_SC_5MG_QW | SEMA_SC_1p0MG_QW | SEMA_PO_14MG_QD | DULA_SC_1p5MG_QW | LIRA_SC_1p8MG_QD | IGLARLIXI2_SC_TIT_QD | INS_DEGLUDEC | SEMA_SC_0p5MG_QW | SEMA_PO_7MG_QD | TIRZ_SC_1MG_QW | DULA_SC_0p75MG_QW | INS_GLARGINE | VISEPE_SC_150UG_QW | EXEN_SC_10UG_BID | SITAGLIPTIN | SEMA_PO_3MG_QD | LIXI_SC_20UG_QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 1.86 1.52 to 2.20 | 1.78 1.45 to 2.11 | 1.58 1.25 to 1.91 | 1.33 1.05 to 1.62 | 1.25 1.00 to 1.48 | 1.08 0.89 to 1.27 | 1.07 0.79 to 1.34 | 1.05 0.72 to 1.38 | 1.00 0.58 to 1.40 | 0.99 0.61 to 1.37 | 0.98 0.69 to 1.24 | 0.95 0.55 to 1.34 | 0.90 0.70 to 1.09 | 0.61 0.35 to 0.87 | 0.57 0.22 to 0.92 | 0.56 0.25 to 0.87 | 0.47 0.22 to 0.70 | 0.41 0.15 to 0.68 | 0.29 0.03 to 0.55 |
| TIRZ_SC_15MG_QW | -1.86 -2.20 to -1.52 | TIRZ_SC_15MG_QW | -0.08 -0.33 to 0.17 | -0.28 -0.53 to -0.02 | -0.52 -0.96 to -0.09 | -0.61 -1.01 to -0.21 | -0.77 -1.11 to -0.43 | -0.79 -1.22 to -0.36 | -0.81 -1.25 to -0.36 | -0.86 -1.18 to -0.55 | -0.87 -1.36 to -0.37 | -0.88 -1.30 to -0.46 | -0.91 -1.29 to -0.54 | -0.96 -1.33 to -0.60 | -1.25 -1.65 to -0.85 | -1.29 -1.78 to -0.81 | -1.30 -1.73 to -0.86 | -1.39 -1.79 to -1.00 | -1.45 -1.86 to -1.03 | -1.57 -1.99 to -1.14 |
| TIRZ_SC_10MG_QW | -1.78 -2.11 to -1.45 | 0.08 -0.17 to 0.33 | TIRZ_SC_10MG_QW | -0.20 -0.46 to 0.05 | -0.45 -0.87 to -0.01 | -0.53 -0.93 to -0.14 | -0.69 -1.03 to -0.37 | -0.70 -1.13 to -0.29 | -0.73 -1.19 to -0.28 | -0.78 -1.10 to -0.47 | -0.79 -1.30 to -0.29 | -0.80 -1.22 to -0.39 | -0.84 -1.21 to -0.46 | -0.88 -1.25 to -0.53 | -1.17 -1.57 to -0.78 | -1.21 -1.69 to -0.73 | -1.22 -1.66 to -0.79 | -1.31 -1.71 to -0.93 | -1.37 -1.78 to -0.95 | -1.49 -1.91 to -1.07 |
| TIRZ_SC_5MG_QW | -1.58 -1.91 to -1.25 | 0.28 0.02 to 0.53 | 0.20 -0.05 to 0.46 | TIRZ_SC_5MG_QW | -0.24 -0.67 to 0.20 | -0.33 -0.72 to 0.06 | -0.50 -0.82 to -0.16 | -0.50 -0.94 to -0.09 | -0.53 -0.99 to -0.07 | -0.58 -0.90 to -0.28 | -0.59 -1.08 to -0.09 | -0.60 -1.02 to -0.18 | -0.63 -1.01 to -0.26 | -0.68 -1.04 to -0.32 | -0.97 -1.36 to -0.56 | -1.01 -1.49 to -0.53 | -1.02 -1.45 to -0.57 | -1.11 -1.51 to -0.72 | -1.16 -1.57 to -0.76 | -1.29 -1.71 to -0.88 |
| SEMA_SC_1p0MG_QW | -1.33 -1.62 to -1.05 | 0.52 0.09 to 0.96 | 0.45 0.01 to 0.87 | 0.24 -0.20 to 0.67 | SEMA_SC_1p0MG_QW | -0.09 -0.39 to 0.22 | -0.25 -0.58 to 0.08 | -0.26 -0.61 to 0.08 | -0.28 -0.69 to 0.14 | -0.33 -0.83 to 0.16 | -0.34 -0.68 to -0.01 | -0.36 -0.69 to -0.03 | -0.39 -0.87 to 0.09 | -0.44 -0.76 to -0.11 | -0.73 -1.09 to -0.35 | -0.77 -1.20 to -0.32 | -0.78 -1.19 to -0.36 | -0.86 -1.14 to -0.60 | -0.92 -1.25 to -0.59 | -1.04 -1.39 to -0.69 |
| SEMA_PO_14MG_QD | -1.25 -1.48 to -1.00 | 0.61 0.21 to 1.01 | 0.53 0.14 to 0.93 | 0.33 -0.06 to 0.72 | 0.09 -0.22 to 0.39 | SEMA_PO_14MG_QD | -0.17 -0.43 to 0.12 | -0.18 -0.44 to 0.09 | -0.20 -0.56 to 0.18 | -0.25 -0.72 to 0.21 | -0.25 -0.65 to 0.11 | -0.27 -0.48 to -0.07 | -0.30 -0.74 to 0.15 | -0.35 -0.60 to -0.10 | -0.64 -0.96 to -0.32 | -0.68 -1.08 to -0.27 | -0.69 -1.05 to -0.32 | -0.78 -0.98 to -0.59 | -0.83 -1.04 to -0.63 | -0.96 -1.26 to -0.65 |
| DULA_SC_1p5MG_QW | -1.08 -1.27 to -0.89 | 0.77 0.43 to 1.11 | 0.69 0.37 to 1.03 | 0.50 0.16 to 0.82 | 0.25 -0.08 to 0.58 | 0.17 -0.12 to 0.43 | DULA_SC_1p5MG_QW | -0.01 -0.33 to 0.30 | -0.03 -0.37 to 0.31 | -0.08 -0.51 to 0.32 | -0.09 -0.51 to 0.32 | -0.11 -0.41 to 0.19 | -0.14 -0.53 to 0.26 | -0.19 -0.38 to -0.01 | -0.47 -0.72 to -0.23 | -0.51 -0.92 to -0.12 | -0.52 -0.83 to -0.22 | -0.62 -0.89 to -0.35 | -0.67 -0.97 to -0.38 | -0.79 -1.09 to -0.50 |
| LIRA_SC_1p8MG_QD | -1.07 -1.34 to -0.79 | 0.79 0.36 to 1.22 | 0.70 0.29 to 1.13 | 0.50 0.09 to 0.94 | 0.26 -0.08 to 0.61 | 0.18 -0.09 to 0.44 | 0.01 -0.30 to 0.33 | LIRA_SC_1p8MG_QD | -0.02 -0.42 to 0.39 | -0.07 -0.55 to 0.42 | -0.08 -0.49 to 0.32 | -0.10 -0.39 to 0.21 | -0.13 -0.59 to 0.35 | -0.18 -0.48 to 0.13 | -0.46 -0.81 to -0.10 | -0.50 -0.94 to -0.05 | -0.51 -0.91 to -0.10 | -0.61 -0.86 to -0.35 | -0.66 -0.95 to -0.34 | -0.78 -1.12 to -0.43 |
| IGLARLIXI2_SC_TIT_QD | -1.05 -1.38 to -0.72 | 0.81 0.36 to 1.25 | 0.73 0.28 to 1.19 | 0.53 0.07 to 0.99 | 0.28 -0.14 to 0.69 | 0.20 -0.18 to 0.56 | 0.03 -0.31 to 0.37 | 0.02 -0.39 to 0.42 | IGLARLIXI2_SC_TIT_QD | -0.05 -0.57 to 0.46 | -0.06 -0.54 to 0.40 | -0.07 -0.47 to 0.31 | -0.11 -0.61 to 0.40 | -0.16 -0.48 to 0.16 | -0.44 -0.73 to -0.15 | -0.48 -0.98 to 0.01 | -0.49 -0.93 to -0.07 | -0.58 -0.96 to -0.23 | -0.64 -1.03 to -0.25 | -0.76 -1.08 to -0.46 |
| INS_DEGLUDEC | -1.00 -1.40 to -0.58 | 0.86 0.55 to 1.18 | 0.78 0.47 to 1.10 | 0.58 0.28 to 0.90 | 0.33 -0.16 to 0.83 | 0.25 -0.21 to 0.72 | 0.08 -0.32 to 0.51 | 0.07 -0.42 to 0.55 | 0.05 -0.46 to 0.57 | INS_DEGLUDEC | -0.01 -0.55 to 0.55 | -0.02 -0.51 to 0.46 | -0.05 -0.48 to 0.39 | -0.10 -0.54 to 0.34 | -0.39 -0.85 to 0.08 | -0.43 -0.97 to 0.12 | -0.44 -0.93 to 0.07 | -0.53 -1.00 to -0.07 | -0.58 -1.06 to -0.09 | -0.71 -1.19 to -0.23 |
| SEMA_SC_0p5MG_QW | -0.99 -1.37 to -0.61 | 0.87 0.37 to 1.36 | 0.79 0.29 to 1.30 | 0.59 0.09 to 1.08 | 0.34 0.01 to 0.68 | 0.25 -0.11 to 0.65 | 0.09 -0.32 to 0.51 | 0.08 -0.32 to 0.49 | 0.06 -0.40 to 0.54 | 0.01 -0.55 to 0.55 | SEMA_SC_0p5MG_QW | -0.02 -0.40 to 0.37 | -0.04 -0.59 to 0.50 | -0.10 -0.50 to 0.32 | -0.38 -0.82 to 0.06 | -0.43 -0.94 to 0.10 | -0.43 -0.91 to 0.06 | -0.53 -0.86 to -0.19 | -0.58 -0.96 to -0.18 | -0.70 -1.12 to -0.27 |
| SEMA_PO_7MG_QD | -0.98 -1.24 to -0.69 | 0.88 0.46 to 1.30 | 0.80 0.39 to 1.22 | 0.60 0.18 to 1.02 | 0.36 0.03 to 0.69 | 0.27 0.07 to 0.48 | 0.11 -0.19 to 0.41 | 0.10 -0.21 to 0.39 | 0.07 -0.31 to 0.47 | 0.02 -0.46 to 0.51 | 0.02 -0.37 to 0.40 | SEMA_PO_7MG_QD | -0.03 -0.50 to 0.44 | -0.08 -0.35 to 0.20 | -0.37 -0.70 to -0.03 | -0.41 -0.83 to 0.03 | -0.42 -0.80 to -0.02 | -0.51 -0.73 to -0.30 | -0.56 -0.77 to -0.35 | -0.69 -1.01 to -0.36 |
| TIRZ_SC_1MG_QW | -0.95 -1.34 to -0.55 | 0.91 0.54 to 1.29 | 0.84 0.46 to 1.21 | 0.63 0.26 to 1.01 | 0.39 -0.09 to 0.87 | 0.30 -0.15 to 0.74 | 0.14 -0.26 to 0.53 | 0.13 -0.35 to 0.59 | 0.11 -0.40 to 0.61 | 0.05 -0.39 to 0.48 | 0.04 -0.50 to 0.59 | 0.03 -0.44 to 0.50 | TIRZ_SC_1MG_QW | -0.05 -0.48 to 0.37 | -0.33 -0.78 to 0.11 | -0.38 -0.91 to 0.14 | -0.39 -0.87 to 0.10 | -0.48 -0.94 to -0.04 | -0.53 -0.99 to -0.06 | -0.65 -1.13 to -0.20 |
| DULA_SC_0p75MG_QW | -0.90 -1.09 to -0.70 | 0.96 0.60 to 1.33 | 0.88 0.53 to 1.25 | 0.68 0.32 to 1.04 | 0.44 0.11 to 0.76 | 0.35 0.10 to 0.60 | 0.19 0.01 to 0.38 | 0.18 -0.13 to 0.48 | 0.16 -0.16 to 0.48 | 0.10 -0.34 to 0.54 | 0.10 -0.32 to 0.50 | 0.08 -0.20 to 0.35 | 0.05 -0.37 to 0.48 | DULA_SC_0p75MG_QW | -0.29 -0.50 to -0.06 | -0.33 -0.72 to 0.08 | -0.34 -0.64 to -0.02 | -0.43 -0.69 to -0.18 | -0.48 -0.76 to -0.21 | -0.61 -0.89 to -0.30 |
| INS_GLARGINE | -0.61 -0.87 to -0.35 | 1.25 0.85 to 1.65 | 1.17 0.78 to 1.57 | 0.97 0.56 to 1.36 | 0.73 0.35 to 1.09 | 0.64 0.32 to 0.96 | 0.47 0.23 to 0.72 | 0.46 0.10 to 0.81 | 0.44 0.15 to 0.73 | 0.39 -0.08 to 0.85 | 0.38 -0.06 to 0.82 | 0.37 0.03 to 0.70 | 0.33 -0.11 to 0.78 | 0.29 0.06 to 0.50 | INS_GLARGINE | -0.04 -0.47 to 0.39 | -0.05 -0.42 to 0.31 | -0.14 -0.47 to 0.16 | -0.19 -0.54 to 0.14 | -0.32 -0.63 to -0.01 |
| VISEPE_SC_150UG_QW | -0.57 -0.92 to -0.22 | 1.29 0.81 to 1.78 | 1.21 0.73 to 1.69 | 1.01 0.53 to 1.49 | 0.77 0.32 to 1.20 | 0.68 0.27 to 1.08 | 0.51 0.12 to 0.92 | 0.50 0.05 to 0.94 | 0.48 -0.01 to 0.98 | 0.43 -0.12 to 0.97 | 0.43 -0.10 to 0.94 | 0.41 -0.03 to 0.83 | 0.38 -0.14 to 0.91 | 0.33 -0.08 to 0.72 | 0.04 -0.39 to 0.47 | VISEPE_SC_150UG_QW | -0.01 -0.47 to 0.47 | -0.10 -0.53 to 0.30 | -0.15 -0.58 to 0.28 | -0.28 -0.71 to 0.15 |
| EXEN_SC_10UG_BID | -0.56 -0.87 to -0.25 | 1.30 0.86 to 1.73 | 1.22 0.79 to 1.66 | 1.02 0.57 to 1.45 | 0.78 0.36 to 1.19 | 0.69 0.32 to 1.05 | 0.52 0.22 to 0.83 | 0.51 0.10 to 0.91 | 0.49 0.07 to 0.93 | 0.44 -0.07 to 0.93 | 0.43 -0.06 to 0.91 | 0.42 0.02 to 0.80 | 0.39 -0.10 to 0.87 | 0.34 0.02 to 0.64 | 0.05 -0.31 to 0.42 | 0.01 -0.47 to 0.47 | EXEN_SC_10UG_BID | -0.09 -0.47 to 0.27 | -0.14 -0.54 to 0.24 | -0.27 -0.66 to 0.12 |
| SITAGLIPTIN | -0.47 -0.70 to -0.22 | 1.39 1.00 to 1.79 | 1.31 0.93 to 1.71 | 1.11 0.72 to 1.51 | 0.86 0.60 to 1.14 | 0.78 0.59 to 0.98 | 0.62 0.35 to 0.89 | 0.61 0.35 to 0.86 | 0.58 0.23 to 0.96 | 0.53 0.07 to 1.00 | 0.53 0.19 to 0.86 | 0.51 0.30 to 0.73 | 0.48 0.04 to 0.94 | 0.43 0.18 to 0.69 | 0.14 -0.16 to 0.47 | 0.10 -0.30 to 0.53 | 0.09 -0.27 to 0.47 | SITAGLIPTIN | -0.05 -0.26 to 0.17 | -0.18 -0.46 to 0.11 |
| SEMA_PO_3MG_QD | -0.41 -0.68 to -0.15 | 1.45 1.03 to 1.86 | 1.37 0.95 to 1.78 | 1.16 0.76 to 1.57 | 0.92 0.59 to 1.25 | 0.83 0.63 to 1.04 | 0.67 0.38 to 0.97 | 0.66 0.34 to 0.95 | 0.64 0.25 to 1.03 | 0.58 0.09 to 1.06 | 0.58 0.18 to 0.96 | 0.56 0.35 to 0.77 | 0.53 0.06 to 0.99 | 0.48 0.21 to 0.76 | 0.19 -0.14 to 0.54 | 0.15 -0.28 to 0.58 | 0.14 -0.24 to 0.54 | 0.05 -0.17 to 0.26 | SEMA_PO_3MG_QD | -0.12 -0.46 to 0.21 |
| LIXI_SC_20UG_QD | -0.29 -0.55 to -0.03 | 1.57 1.14 to 1.99 | 1.49 1.07 to 1.91 | 1.29 0.88 to 1.71 | 1.04 0.69 to 1.39 | 0.96 0.65 to 1.26 | 0.79 0.50 to 1.09 | 0.78 0.43 to 1.12 | 0.76 0.46 to 1.08 | 0.71 0.23 to 1.19 | 0.70 0.27 to 1.12 | 0.69 0.36 to 1.01 | 0.65 0.20 to 1.13 | 0.61 0.30 to 0.89 | 0.32 0.01 to 0.63 | 0.28 -0.15 to 0.71 | 0.27 -0.12 to 0.66 | 0.18 -0.11 to 0.46 | 0.12 -0.21 to 0.46 | LIXI_SC_20UG_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.
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 HbA1c (percent) effect modifier, prognostic factor; 19 of 19 | Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 19 of 19 | Diabetes duration (years) effect modifier, prognostic factor; 18 of 19 | Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 17 of 19 | Age (years) prognostic factor; 19 of 19 | Treatment duration (weeks) effect modifier; 19 of 19 |
|---|---|---|---|---|---|---|
| NCT03131687 S000010 | 8.13 | S1 | 8.51 | 1.66 | 57.2 | 26 |
| PIONEER 4 S000133 | 7.98 | S1 | 7.6 | 13.4 | 56.2 | 52 |
| NCT01476475 S000191 | 8.05 | S1 | 6.7 | 0.62 | 56.75 | 24 |
| PIONEER 10 S000234 | 8.31 | S1 | 9.36 | 100 | 58.43 | 52 |
| NCT01584232 S000246 | 8.05 | S1 | 8.85 | 100 | 56.8 | 26 |
| AWARD-10 S000305 | 8.04 | S1 | 9.38 | not reported | 57.27 | 24 |
| NCT00976937 S000415 | 8.13 | S1 | 4.4 | 0.6 | 43.05 | 24 |
| SUSTAIN 9 S000483 | 8.05 | S1 | 9.7 | 23.51 | 57.05 | 30 |
| PIONEER 12 S000522 | 8.12 | S1 | 5.63 | 75.22 | 53.25 | 26 |
| AWARD-8 S001068 | 8.4 | S1 | 7.6 | 1.7 | 57.8 | 24 |
| LIRA-SWITCH™ S001119 | 8.25 | S1 | 7.75 | not reported | 56.4 | 26 |
| AWARD-2 S001130 | 8.14 | S1 | 9.1 | 16.91 | 56.66 | 78 |
| NCT04504396 S001230 | 8.47 | S1 | 5.14 | 100 region: all sites in Asia | 53.2 | 24 |
| SUSTAIN S001311 | 8.1 | S1 | 6.37 | 85.03 | 53.03 | 30 |
| SURPASS-3 S001591 | 8.17 | S1 | 8.4 | 5.4 | 57.4 | 52 |
| LIXILAN JP-O1 S002018 | 8.39 | S1 | 8.67 | 100 region: all sites in Asia | 58 | 52 |
| AWARD-1 S002153 | 8.07 | S1 | 8.77 | 2.45 | 55.65 | 52 |
| GETGOAL-M S002188 | 8.05 | S1 | 6.2 | 8.2 | 54.65 | 24 |
| PIONEER 3 S002267 | 8.33 | S1 | not reported | 13.14 | 57.75 | 78 |
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, Diabetes duration: design means range from 4.4 (LIXI_SC_20UG_QD vs SITAGLIPTIN) to 9.7 (PLACEBO vs SEMA_SC_1p0MG_QW) years; threshold 3
- FlagBaseline, Asian ancestry or region: design means range from 0.6 (LIXI_SC_20UG_QD vs SITAGLIPTIN) to 100.0 (DULA_SC_0p75MG_QW vs INS_GLARGINE) percent Asian; threshold 30
- FlagBaseline, Age: design means range from 43.1 (LIXI_SC_20UG_QD vs SITAGLIPTIN) to 58.4 (DULA_SC_0p75MG_QW vs SEMA_PO_14MG_QD vs SEMA_PO_3MG_QD vs SEMA_PO_7MG_QD) years; threshold 10
- FlagBaseline, Treatment duration: design means range from 24.0 (DULA_SC_0p75MG_QW vs DULA_SC_1p5MG_QW vs PLACEBO) to 78.0 (DULA_SC_0p75MG_QW vs DULA_SC_1p5MG_QW vs INS_GLARGINE) weeks; threshold 26
- NoteOutcome assessment, time point: selected time points span 24 to 30 weeks
- NoteOutcome assessment, analysis set: mixed: full_analysis 9, modified_itt 10
- NoteOutcome assessment, definition: mixed: change in HbA1c from baseline to week 26, LOCF 1, not stated 18
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 12, not stated 6, treatment_policy 1
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 18, not stated 1
- NoteRisk of bias, blinding: mixed: double_blind 13, open_label 5, single_blind 1
- NoteData handling, input conversions: arms_combined 1, n_randomized 8
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03131687 | 26 | modified_itt | not stated | not stated | not stated | not stated | treatment_policy | hypothetical | double_blind | industry | 2017 | age 18 to 75; T2D at least 6 months; HbA1c 7.0 to 10.5%; BMI 23 to 50; diet and exercise or metformin |
| PIONEER 4 | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2016 | Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more |
| NCT01476475 | 24 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2011 | Adults with T2D; HbA1c 7 to 10 percent on metformin at least 1.5 g/day; insulin naive |
| PIONEER 10 | 26 | full_analysis | 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 |
| NCT01584232 | 26 | full_analysis | not stated | not stated | not stated | not stated | not stated | hypothetical | open_label | industry | 2012 | Japanese adults 20 years or older; BMI 18.5 to less than 35 kg/m2; HbA1c 7.0 to 10.0 percent; on sulfonylurea and/or biguanide |
| AWARD-10 | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | double_blind | industry | 2015 | T2D; HbA1c 7.0 to 9.5 percent; BMI 45 or lower; SGLT2i with or without metformin |
| NCT00976937 | 24 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2009 | age 18 to under 50; BMI 30 or more; HbA1c 7.0 to 10 percent; metformin at least 1.5 g/day |
| SUSTAIN 9 | 30 | full_analysis | not stated | 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 | 26 | full_analysis | not stated | 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 |
| AWARD-8 | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | double_blind | industry | 2013 | age 18 or older; BMI up to 45; HbA1c 7.5 to 9.5 percent on sulfonylurea at least half maximal dose |
| 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 |
| AWARD-2 | 26 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | open_label | industry | 2010 | type 2 diabetes on metformin and glimepiride |
| NCT04504396 | 24 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2020 | age 18 to 75; HbA1c 7.0 to 10.5 percent; BMI 40 or lower; eGFR 60 or higher; metformin monotherapy at least 1000 mg |
| 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 |
| SURPASS-3 | 24 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2019 | insulin naive; HbA1c 7.0 to 10.5 percent; BMI at least 25; metformin with or without SGLT2i; eGFR above 45 |
| LIXILAN JP-O1 | 26 | modified_itt | change in HbA1c from baseline to week 26, LOCF | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2016 | insulin naive Japanese adults; HbA1c 7.5 to 10%; FPG 13.8 mmol/L or less; one or two OADs |
| AWARD-1 | 26 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | double_blind | industry | 2010 | adults with type 2 diabetes on metformin and pioglitazone |
| GETGOAL-M | 24 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2008 | type 2 diabetes on metformin 1.5 g/day or more for 3 months; HbA1c 7 to 10 percent; FPG 13.9 mmol/L or less |
| PIONEER 3 | 26 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2016 | adults with T2D; HbA1c 7.0 to 10.5 percent; metformin with or without sulfonylurea |
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 |
|---|---|---|---|---|---|---|---|---|---|
| NCT03131687 | A1 | PLACEBO | 26 | arm, change | -0.060 | 0.140 | 44 | R0016215:Supplement Table 1 | |
| NCT03131687 | A2 | TIRZ_SC_1MG_QW | 26 | arm, change | -1.060 | 0.110 | 45 | R0016215:Supplement Table 1 | |
| NCT03131687 | A3 | TIRZ_SC_5MG_QW | 26 | arm, change | -1.730 | 0.080 | 52 | R0016215:Supplement Table 1 | |
| NCT03131687 | A4 | TIRZ_SC_10MG_QW | 26 | arm, change | -1.890 | 0.080 | 47 | R0016215:Supplement Table 1 | |
| NCT03131687 | A5 | TIRZ_SC_15MG_QW | 26 | arm, change | -1.940 | 0.090 | 44 | R0016215:Supplement Table 1 | |
| NCT03131687 | A6 | DULA_SC_1p5MG_QW | 26 | arm, change | -1.210 | 0.140 | 49 | R0016215:Supplement Table 1 | |
| PIONEER 4 | A1 | SEMA_PO_14MG_QD | 26 | arm, change | -1.400 | 0.053 | 285 | registry:outcomes | |
| PIONEER 4 | A2 | LIRA_SC_1p8MG_QD | 26 | arm, change | -1.200 | 0.053 | 284 | registry:outcomes | |
| PIONEER 4 | A3 | PLACEBO | 26 | arm, change | -0.100 | 0.059 | 142 | registry:outcomes | |
| NCT01476475 | A1 | IGLARLIXI2_SC_TIT_QD | 24 | arm, change | -1.820 | 0.058 | 160 | registry:outcomes | |
| NCT01476475 | A2 | INS_GLARGINE | 24 | arm, change | -1.640 | 0.057 | 161 | registry:outcomes | |
| PIONEER 10 | A1 | SEMA_PO_3MG_QD | 26 | arm, change | -1.100 | 0.100 | 126 | R0018421:Figure 2D | |
| PIONEER 10 | A2 | SEMA_PO_7MG_QD | 26 | arm, change | -1.700 | 0.100 | 124 | R0018421:Figure 2D | |
| PIONEER 10 | A3 | SEMA_PO_14MG_QD | 26 | arm, change | -2.000 | 0.100 | 120 | R0018421:Figure 2D | |
| PIONEER 10 | A4 | DULA_SC_0p75MG_QW | 26 | arm, change | -1.600 | 0.100 | 62 | R0018421:Figure 2D | |
| NCT01584232 | A1 | DULA_SC_0p75MG_QW | 26 | arm, change | -1.440 | 0.050 | 178 | R0016159:Table 2 | |
| NCT01584232 | A2 | INS_GLARGINE | 26 | arm, change | -0.900 | 0.050 | 179 | R0016159:Table 2 | |
| AWARD-10 | A1 | DULA_SC_1p5MG_QW | 24 | arm, change | -1.330 | 0.063 | 130 | registry:outcomes | |
| AWARD-10 | A2 | DULA_SC_0p75MG_QW | 24 | arm, change | -1.190 | 0.063 | 131 | registry:outcomes | |
| AWARD-10 | A3 | PLACEBO | 24 | arm, change | -0.510 | 0.065 | 123 | registry:outcomes | |
| NCT00976937 | A1 | LIXI_SC_20UG_QD | 24 | arm, change | -0.700 | 0.100 | 150 | R0012687:Results | |
| NCT00976937 | A2 | SITAGLIPTIN | 24 | arm, change | -0.700 | 0.100 | 160 | R0012687:Results | |
| SUSTAIN 9 | A1 | SEMA_SC_1p0MG_QW | 30 | contrast, md | -1.420 | 0.094 | R0021710:Figure 1 | ||
| SUSTAIN 9 | A2 | PLACEBO | 30 | contrast, md | R0021710:Figure 1 | ||||
| PIONEER 12 | A1 | SEMA_PO_3MG_QD | 26 | arm, change | -0.800 | 0.053 | 361 | n_randomized | registry:outcomes |
| PIONEER 12 | A2 | SEMA_PO_7MG_QD | 26 | arm, change | -1.300 | 0.053 | 360 | n_randomized | registry:outcomes |
| PIONEER 12 | A3 | SEMA_PO_14MG_QD | 26 | arm, change | -1.600 | 0.053 | 361 | n_randomized | registry:outcomes |
| PIONEER 12 | A4 | SITAGLIPTIN | 26 | arm, change | -0.700 | 0.053 | 359 | n_randomized | registry:outcomes |
| AWARD-8 | A1 | DULA_SC_1p5MG_QW | 24 | arm, change | -1.380 | 0.080 | 215 | registry:outcomes | |
| AWARD-8 | A2 | PLACEBO | 24 | arm, change | -0.110 | 0.140 | 53 | registry:outcomes | |
| LIRA-SWITCH™ | A1 | LIRA_SC_1p8MG_QD | 26 | contrast, md | -0.610 | 0.107 | R0025720:Results | ||
| LIRA-SWITCH™ | A2 | SITAGLIPTIN | 26 | contrast, md | R0025720:Results | ||||
| AWARD-2 | A1 | DULA_SC_1p5MG_QW | 26 | arm, change | -1.160 | 0.060 | 263 | registry:outcomes | |
| AWARD-2 | A2 | DULA_SC_0p75MG_QW | 26 | arm, change | -0.890 | 0.050 | 266 | registry:outcomes | |
| AWARD-2 | A3 | INS_GLARGINE | 26 | arm, change | -0.650 | 0.060 | 258 | registry:outcomes | |
| NCT04504396 | A1 | VISEPE_SC_150UG_QW | 24 | arm, change | -1.270 | 0.054 | 310 | R0009432:Table 2 | |
| NCT04504396 | A2 | PLACEBO | 24 | arm, change | -0.700 | 0.051 | 310 | R0009432:Table 2 | |
| SUSTAIN | A1 | SEMA_SC_0p5MG_QW | 30 | arm, change | -1.500 | 0.065 | 288 | registry:outcomes | |
| SUSTAIN | A2 | SEMA_SC_1p0MG_QW | 30 | arm, change | -1.800 | 0.053 | 290 | registry:outcomes | |
| SUSTAIN | A3 | SITAGLIPTIN | 30 | arm, change | -1.000 | 0.053 | 290 | registry:outcomes | |
| SURPASS-3 | A1 | TIRZ_SC_5MG_QW | 24 | arm, change | -1.910 | 0.044 | 359 | n_randomized | R0007660:Table 1 |
| SURPASS-3 | A2 | TIRZ_SC_10MG_QW | 24 | arm, change | -2.140 | 0.045 | 361 | n_randomized | R0007660:Table 1 |
| SURPASS-3 | A3 | TIRZ_SC_15MG_QW | 24 | arm, change | -2.240 | 0.045 | 359 | n_randomized | R0007660:Table 1 |
| SURPASS-3 | A4 | INS_DEGLUDEC | 24 | arm, change | -1.360 | 0.045 | 365 | n_randomized | R0007660:Table 1 |
| LIXILAN JP-O1 | A1 | IGLARLIXI2_SC_TIT_QD | 26 | arm, change | -1.580 | 0.072 | 161 | R0015751:Table 2 | |
| LIXILAN JP-O1 | A2 | LIXI_SC_20UG_QD | 26 | arm, change | -0.510 | 0.073 | 160 | R0015751:Table 2 | |
| AWARD-1 | A1 | DULA_SC_1p5MG_QW | 26 | arm, change | -1.510 | 0.060 | 271 | registry:outcomes | |
| AWARD-1 | A2 | DULA_SC_0p75MG_QW | 26 | arm, change | -1.300 | 0.060 | 269 | registry:outcomes | |
| AWARD-1 | A3 | EXEN_SC_10UG_BID | 26 | arm, change | -0.990 | 0.060 | 266 | registry:outcomes | |
| AWARD-1 | A4 | PLACEBO | 26 | arm, change | -0.460 | 0.080 | 119 | registry:outcomes | |
| GETGOAL-M | A1+A2 | LIXI_SC_20UG_QD | 24 | arm, change | -0.851 | 0.050 | 483 | arms_combined | R0025872:Results |
| GETGOAL-M | A3 | PLACEBO | 24 | arm, change | -0.400 | 0.080 | 164 | R0025872:Results | |
| PIONEER 3 | A1 | SEMA_PO_3MG_QD | 26 | arm, change | -0.600 | 0.046 | 466 | registry:outcomes | |
| PIONEER 3 | A2 | SEMA_PO_7MG_QD | 26 | arm, change | -1.200 | 0.051 | 465 | registry:outcomes | |
| PIONEER 3 | A3 | SEMA_PO_14MG_QD | 26 | arm, change | -1.400 | 0.046 | 465 | registry:outcomes | |
| PIONEER 3 | A4 | SITAGLIPTIN | 26 | arm, change | -0.800 | 0.042 | 467 | registry:outcomes |
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