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)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean difference
13
Randomized trials
20
Treatments
8,598
Participants
36
Trial arms
In plain language
Across 13 trials with 8,598 participants, 16 of 19 treatments had a clearly better result than placebo on HbA1c change, and for 3 the evidence could not tell them apart from placebo. The most favorable estimate was for Tirzepatide 15 mg subcutaneous once weekly: mean difference -2.26 percentage points (95% credible interval -2.74 to -1.65).
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 | -2.26 (-2.74 to -1.65) | -2.77 to -1.60 | -2.39 (-2.81 to -1.98) | Better |
| Tirzepatide 10 mg subcutaneous once weekly TIRZ_SC_10MG_QW | -2.13 (-2.61 to -1.54) | -2.65 to -1.48 | -2.27 (-2.68 to -1.85) | Better |
| Orforglipron 36 mg oral once daily ORFO_PO_36MG_QD | -2.04 (-2.39 to -1.61) | -2.43 to -1.54 | -2.10 (-2.37 to -1.84) | Better |
| Tirzepatide 5 mg subcutaneous once weekly TIRZ_SC_5MG_QW | -1.89 (-2.37 to -1.29) | -2.41 to -1.23 | -2.02 (-2.44 to -1.60) | Better |
| Semaglutide 2.0 mg subcutaneous once weekly SEMA_SC_2p0MG_QW | -1.81 (-2.67 to -0.97) | -2.71 to -0.93 | -2.00 (-2.90 to -1.10) | Better |
| Orforglipron 12 mg oral once daily ORFO_PO_12MG_QD | -1.79 (-2.14 to -1.34) | -2.17 to -1.25 | -1.85 (-2.12 to -1.58) | Better |
| Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW | -1.60 (-2.47 to -0.74) | -2.51 to -0.69 | -1.80 (-2.71 to -0.89) | Better |
| Dulaglutide 4.5 mg subcutaneous once weekly DULA_SC_4p5MG_QW | -1.43 (-1.88 to -0.87) | -1.93 to -0.80 | -1.54 (-1.93 to -1.15) | Better |
| Semaglutide 14 mg oral once daily (original tablet) SEMA_PO_14MG_QD | -1.35 (-1.60 to -1.02) | -1.68 to -0.93 | -1.40 (-1.61 to -1.19) | Better |
| Insulin degludec INS_DEGLUDEC | -1.27 (-1.77 to -0.63) | -1.79 to -0.58 | -1.40 (-1.83 to -0.97) | Better |
| Dulaglutide 1.5 mg subcutaneous once weekly DULA_SC_1p5MG_QW | -1.13 (-1.52 to -0.61) | -1.55 to -0.56 | -1.23 (-1.59 to -0.87) | Better |
| Exenatide extended release 2 mg subcutaneous once weekly EXENER_SC_2MG_QW | -0.98 (-1.87 to -0.06) | -1.89 to -0.03 | -1.18 (-2.11 to -0.25) | Better |
| Semaglutide 7 mg oral once daily (original tablet) SEMA_PO_7MG_QD | -0.98 (-1.29 to -0.57) | -1.35 to -0.48 | -1.04 (-1.30 to -0.78) | Better |
| Canagliflozin CANAGLIFLOZIN | -0.90 (-1.81 to 0.03) | -1.84 to 0.06 | -1.10 (-2.03 to -0.17) | Unclear |
| Dulaglutide 0.75 mg subcutaneous once weekly DULA_SC_0p75MG_QW | -0.83 (-1.19 to -0.35) | -1.23 to -0.30 | -0.92 (-1.25 to -0.59) | Better |
| Insulin glargine INS_GLARGINE | -0.68 (-1.08 to -0.14) | -1.12 to -0.07 | -0.79 (-1.16 to -0.41) | Better |
| Exenatide 10 ug subcutaneous twice daily EXEN_SC_10UG_BID | -0.56 (-0.99 to -0.02) | -1.02 to 0.06 | -0.66 (-1.06 to -0.27) | Better |
| Albiglutide flexible dose injection once weekly ALBI_SC_FLEX_30-50_QW | -0.55 (-1.03 to 0.04) | -1.07 to 0.09 | -0.67 (-1.07 to -0.26) | Unclear |
| Semaglutide 3 mg oral once daily (original tablet) SEMA_PO_3MG_QD | -0.25 (-0.64 to 0.20) | -0.68 to 0.26 | -0.32 (-0.65 to 0.01) | 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 | TIRZ_SC_15MG_QW | TIRZ_SC_10MG_QW | ORFO_PO_36MG_QD | TIRZ_SC_5MG_QW | SEMA_SC_2p0MG_QW | ORFO_PO_12MG_QD | SEMA_SC_1p0MG_QW | DULA_SC_4p5MG_QW | SEMA_PO_14MG_QD | INS_DEGLUDEC | DULA_SC_1p5MG_QW | EXENER_SC_2MG_QW | SEMA_PO_7MG_QD | CANAGLIFLOZIN | DULA_SC_0p75MG_QW | INS_GLARGINE | EXEN_SC_10UG_BID | ALBI_SC_FLEX_30-50_QW | SEMA_PO_3MG_QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 2.26 1.65 to 2.74 | 2.13 1.54 to 2.61 | 2.04 1.61 to 2.39 | 1.89 1.29 to 2.37 | 1.81 0.97 to 2.67 | 1.79 1.34 to 2.14 | 1.60 0.74 to 2.47 | 1.43 0.87 to 1.88 | 1.35 1.02 to 1.60 | 1.27 0.63 to 1.77 | 1.13 0.61 to 1.52 | 0.98 0.06 to 1.87 | 0.98 0.57 to 1.29 | 0.90 -0.03 to 1.81 | 0.83 0.35 to 1.19 | 0.68 0.14 to 1.08 | 0.56 0.02 to 0.99 | 0.55 -0.04 to 1.03 | 0.25 -0.20 to 0.64 |
| TIRZ_SC_15MG_QW | -2.26 -2.74 to -1.65 | TIRZ_SC_15MG_QW | -0.13 -0.31 to 0.07 | -0.23 -0.70 to 0.32 | -0.37 -0.54 to -0.16 | -0.45 -1.45 to 0.62 | -0.48 -0.96 to 0.08 | -0.66 -1.66 to 0.42 | -0.83 -1.26 to -0.38 | -0.91 -1.34 to -0.39 | -0.99 -1.23 to -0.75 | -1.14 -1.49 to -0.75 | -1.28 -2.34 to -0.18 | -1.29 -1.72 to -0.79 | -1.35 -2.42 to -0.24 | -1.44 -1.78 to -1.04 | -1.59 -1.83 to -1.30 | -1.70 -2.13 to -1.25 | -1.71 -2.06 to -1.30 | -2.01 -2.46 to -1.49 |
| TIRZ_SC_10MG_QW | -2.13 -2.61 to -1.54 | 0.13 -0.07 to 0.31 | TIRZ_SC_10MG_QW | -0.10 -0.57 to 0.44 | -0.24 -0.43 to -0.05 | -0.32 -1.32 to 0.73 | -0.35 -0.83 to 0.20 | -0.53 -1.55 to 0.52 | -0.70 -1.13 to -0.27 | -0.79 -1.22 to -0.28 | -0.87 -1.11 to -0.63 | -1.01 -1.36 to -0.62 | -1.15 -2.21 to -0.07 | -1.16 -1.61 to -0.66 | -1.23 -2.27 to -0.14 | -1.31 -1.65 to -0.93 | -1.46 -1.72 to -1.19 | -1.58 -2.00 to -1.11 | -1.58 -1.94 to -1.20 | -1.89 -2.33 to -1.37 |
| ORFO_PO_36MG_QD | -2.04 -2.39 to -1.61 | 0.23 -0.32 to 0.70 | 0.10 -0.44 to 0.57 | ORFO_PO_36MG_QD | -0.14 -0.70 to 0.35 | -0.23 -1.14 to 0.74 | -0.25 -0.52 to 0.00 | -0.44 -1.37 to 0.55 | -0.60 -1.10 to -0.16 | -0.69 -0.93 to -0.43 | -0.77 -1.35 to -0.26 | -0.91 -1.35 to -0.51 | -1.06 -2.03 to -0.04 | -1.06 -1.32 to -0.81 | -1.14 -2.13 to -0.10 | -1.21 -1.61 to -0.86 | -1.36 -1.84 to -0.95 | -1.48 -1.96 to -1.04 | -1.48 -2.03 to -1.01 | -1.79 -2.16 to -1.42 |
| TIRZ_SC_5MG_QW | -1.89 -2.37 to -1.29 | 0.37 0.16 to 0.54 | 0.24 0.05 to 0.43 | 0.14 -0.35 to 0.70 | TIRZ_SC_5MG_QW | -0.08 -1.08 to 0.99 | -0.11 -0.60 to 0.44 | -0.28 -1.29 to 0.77 | -0.46 -0.90 to -0.03 | -0.55 -0.98 to -0.04 | -0.63 -0.88 to -0.39 | -0.77 -1.13 to -0.39 | -0.91 -1.98 to 0.16 | -0.92 -1.37 to -0.43 | -0.99 -2.04 to 0.10 | -1.07 -1.42 to -0.69 | -1.22 -1.47 to -0.94 | -1.34 -1.77 to -0.88 | -1.34 -1.70 to -0.96 | -1.64 -2.11 to -1.12 |
| SEMA_SC_2p0MG_QW | -1.81 -2.67 to -0.97 | 0.45 -0.62 to 1.45 | 0.32 -0.73 to 1.32 | 0.23 -0.74 to 1.14 | 0.08 -0.99 to 1.08 | SEMA_SC_2p0MG_QW | -0.03 -1.00 to 0.91 | -0.21 -0.47 to 0.03 | -0.38 -1.40 to 0.60 | -0.46 -1.40 to 0.43 | -0.55 -1.63 to 0.46 | -0.69 -1.69 to 0.25 | -0.83 -1.20 to -0.48 | -0.83 -1.80 to 0.08 | -0.91 -1.28 to -0.56 | -0.99 -1.98 to -0.04 | -1.14 -2.17 to -0.18 | -1.26 -2.28 to -0.29 | -1.26 -2.32 to -0.28 | -1.57 -2.56 to -0.63 |
| ORFO_PO_12MG_QD | -1.79 -2.14 to -1.34 | 0.48 -0.08 to 0.96 | 0.35 -0.20 to 0.83 | 0.25 -0.00 to 0.52 | 0.11 -0.44 to 0.60 | 0.03 -0.91 to 1.00 | ORFO_PO_12MG_QD | -0.19 -1.15 to 0.81 | -0.35 -0.86 to 0.11 | -0.44 -0.68 to -0.17 | -0.52 -1.09 to -0.01 | -0.66 -1.11 to -0.25 | -0.81 -1.79 to 0.21 | -0.81 -1.07 to -0.55 | -0.88 -1.89 to 0.14 | -0.96 -1.35 to -0.60 | -1.11 -1.59 to -0.69 | -1.23 -1.72 to -0.78 | -1.23 -1.78 to -0.74 | -1.54 -1.91 to -1.16 |
| SEMA_SC_1p0MG_QW | -1.60 -2.47 to -0.74 | 0.66 -0.42 to 1.66 | 0.53 -0.52 to 1.55 | 0.44 -0.55 to 1.37 | 0.28 -0.77 to 1.29 | 0.21 -0.03 to 0.47 | 0.19 -0.81 to 1.15 | SEMA_SC_1p0MG_QW | -0.17 -1.22 to 0.84 | -0.25 -1.21 to 0.65 | -0.34 -1.42 to 0.67 | -0.48 -1.50 to 0.49 | -0.62 -0.90 to -0.36 | -0.62 -1.61 to 0.30 | -0.70 -0.96 to -0.44 | -0.78 -1.78 to 0.18 | -0.93 -1.97 to 0.05 | -1.04 -2.08 to -0.07 | -1.05 -2.13 to -0.04 | -1.36 -2.37 to -0.41 |
| DULA_SC_4p5MG_QW | -1.43 -1.88 to -0.87 | 0.83 0.38 to 1.26 | 0.70 0.27 to 1.13 | 0.60 0.16 to 1.10 | 0.46 0.03 to 0.90 | 0.38 -0.60 to 1.40 | 0.35 -0.11 to 0.86 | 0.17 -0.84 to 1.22 | DULA_SC_4p5MG_QW | -0.08 -0.49 to 0.38 | -0.17 -0.64 to 0.30 | -0.31 -0.56 to -0.06 | -0.45 -1.50 to 0.65 | -0.46 -0.87 to 0.00 | -0.53 -1.57 to 0.53 | -0.61 -0.90 to -0.28 | -0.76 -1.10 to -0.41 | -0.87 -1.24 to -0.50 | -0.88 -1.29 to -0.45 | -1.18 -1.63 to -0.70 |
| SEMA_PO_14MG_QD | -1.35 -1.60 to -1.02 | 0.91 0.39 to 1.34 | 0.79 0.28 to 1.22 | 0.69 0.43 to 0.93 | 0.55 0.04 to 0.98 | 0.46 -0.43 to 1.40 | 0.44 0.17 to 0.68 | 0.25 -0.65 to 1.21 | 0.08 -0.38 to 0.49 | SEMA_PO_14MG_QD | -0.08 -0.63 to 0.38 | -0.23 -0.62 to 0.11 | -0.37 -1.30 to 0.60 | -0.37 -0.59 to -0.17 | -0.45 -1.43 to 0.54 | -0.52 -0.86 to -0.23 | -0.67 -1.11 to -0.32 | -0.79 -1.25 to -0.40 | -0.79 -1.30 to -0.36 | -1.10 -1.42 to -0.79 |
| INS_DEGLUDEC | -1.27 -1.77 to -0.63 | 0.99 0.75 to 1.23 | 0.87 0.63 to 1.11 | 0.77 0.26 to 1.35 | 0.63 0.39 to 0.88 | 0.55 -0.46 to 1.63 | 0.52 0.01 to 1.09 | 0.34 -0.67 to 1.42 | 0.17 -0.30 to 0.64 | 0.08 -0.38 to 0.63 | INS_DEGLUDEC | -0.14 -0.54 to 0.28 | -0.29 -1.35 to 0.82 | -0.29 -0.77 to 0.24 | -0.36 -1.42 to 0.75 | -0.44 -0.83 to -0.02 | -0.60 -0.90 to -0.24 | -0.71 -1.18 to -0.21 | -0.72 -1.10 to -0.28 | -1.02 -1.50 to -0.46 |
| DULA_SC_1p5MG_QW | -1.13 -1.52 to -0.61 | 1.14 0.75 to 1.49 | 1.01 0.62 to 1.36 | 0.91 0.51 to 1.35 | 0.77 0.39 to 1.13 | 0.69 -0.25 to 1.69 | 0.66 0.25 to 1.11 | 0.48 -0.49 to 1.50 | 0.31 0.06 to 0.56 | 0.23 -0.11 to 0.62 | 0.14 -0.28 to 0.54 | DULA_SC_1p5MG_QW | -0.14 -1.15 to 0.90 | -0.15 -0.50 to 0.24 | -0.22 -1.23 to 0.82 | -0.30 -0.49 to -0.10 | -0.45 -0.71 to -0.21 | -0.57 -0.85 to -0.29 | -0.57 -0.92 to -0.21 | -0.88 -1.25 to -0.47 |
| EXENER_SC_2MG_QW | -0.98 -1.87 to -0.06 | 1.28 0.18 to 2.34 | 1.15 0.07 to 2.21 | 1.06 0.04 to 2.03 | 0.91 -0.16 to 1.98 | 0.83 0.48 to 1.20 | 0.81 -0.21 to 1.79 | 0.62 0.36 to 0.90 | 0.45 -0.65 to 1.50 | 0.37 -0.60 to 1.30 | 0.29 -0.82 to 1.35 | 0.14 -0.90 to 1.15 | EXENER_SC_2MG_QW | -0.00 -1.01 to 0.97 | -0.08 -0.46 to 0.30 | -0.16 -1.20 to 0.83 | -0.31 -1.37 to 0.73 | -0.43 -1.49 to 0.60 | -0.43 -1.52 to 0.62 | -0.73 -1.77 to 0.26 |
| SEMA_PO_7MG_QD | -0.98 -1.29 to -0.57 | 1.29 0.79 to 1.72 | 1.16 0.66 to 1.61 | 1.06 0.81 to 1.32 | 0.92 0.43 to 1.37 | 0.83 -0.08 to 1.80 | 0.81 0.55 to 1.07 | 0.62 -0.30 to 1.61 | 0.46 -0.00 to 0.87 | 0.37 0.17 to 0.59 | 0.29 -0.24 to 0.77 | 0.15 -0.24 to 0.50 | 0.00 -0.97 to 1.01 | SEMA_PO_7MG_QD | -0.07 -1.07 to 0.93 | -0.15 -0.47 to 0.16 | -0.30 -0.72 to 0.08 | -0.42 -0.85 to -0.02 | -0.42 -0.91 to 0.04 | -0.72 -1.04 to -0.41 |
| CANAGLIFLOZIN | -0.90 -1.81 to 0.03 | 1.35 0.24 to 2.42 | 1.23 0.14 to 2.27 | 1.14 0.10 to 2.13 | 0.99 -0.10 to 2.04 | 0.91 0.56 to 1.28 | 0.88 -0.14 to 1.89 | 0.70 0.44 to 0.96 | 0.53 -0.53 to 1.57 | 0.45 -0.54 to 1.43 | 0.36 -0.75 to 1.42 | 0.22 -0.82 to 1.23 | 0.08 -0.30 to 0.46 | 0.07 -0.93 to 1.07 | CANAGLIFLOZIN | -0.07 -1.11 to 0.93 | -0.23 -1.29 to 0.79 | -0.35 -1.39 to 0.69 | -0.35 -1.46 to 0.70 | -0.66 -1.69 to 0.35 |
| DULA_SC_0p75MG_QW | -0.83 -1.19 to -0.35 | 1.44 1.04 to 1.78 | 1.31 0.93 to 1.65 | 1.21 0.86 to 1.61 | 1.07 0.69 to 1.42 | 0.99 0.04 to 1.98 | 0.96 0.60 to 1.35 | 0.78 -0.18 to 1.78 | 0.61 0.28 to 0.90 | 0.52 0.23 to 0.86 | 0.44 0.02 to 0.83 | 0.30 0.10 to 0.49 | 0.16 -0.83 to 1.20 | 0.15 -0.16 to 0.47 | 0.07 -0.93 to 1.11 | DULA_SC_0p75MG_QW | -0.15 -0.41 to 0.09 | -0.27 -0.56 to 0.00 | -0.27 -0.63 to 0.07 | -0.58 -0.91 to -0.22 |
| INS_GLARGINE | -0.68 -1.08 to -0.14 | 1.59 1.30 to 1.83 | 1.46 1.19 to 1.72 | 1.36 0.95 to 1.84 | 1.22 0.94 to 1.47 | 1.14 0.18 to 2.17 | 1.11 0.69 to 1.59 | 0.93 -0.05 to 1.97 | 0.76 0.41 to 1.10 | 0.67 0.32 to 1.11 | 0.60 0.24 to 0.90 | 0.45 0.21 to 0.71 | 0.31 -0.73 to 1.37 | 0.30 -0.08 to 0.72 | 0.23 -0.79 to 1.29 | 0.15 -0.09 to 0.41 | INS_GLARGINE | -0.12 -0.47 to 0.25 | -0.12 -0.38 to 0.14 | -0.43 -0.81 to 0.02 |
| EXEN_SC_10UG_BID | -0.56 -0.99 to -0.02 | 1.70 1.25 to 2.13 | 1.58 1.11 to 2.00 | 1.48 1.04 to 1.96 | 1.34 0.88 to 1.77 | 1.26 0.29 to 2.28 | 1.23 0.78 to 1.72 | 1.04 0.07 to 2.08 | 0.87 0.50 to 1.24 | 0.79 0.40 to 1.25 | 0.71 0.21 to 1.18 | 0.57 0.29 to 0.85 | 0.43 -0.60 to 1.49 | 0.42 0.02 to 0.85 | 0.35 -0.69 to 1.39 | 0.27 -0.00 to 0.56 | 0.12 -0.25 to 0.47 | EXEN_SC_10UG_BID | -0.01 -0.43 to 0.44 | -0.31 -0.72 to 0.14 |
| ALBI_SC_FLEX_30-50_QW | -0.55 -1.03 to 0.04 | 1.71 1.30 to 2.06 | 1.58 1.20 to 1.94 | 1.48 1.01 to 2.03 | 1.34 0.96 to 1.70 | 1.26 0.28 to 2.32 | 1.23 0.74 to 1.78 | 1.05 0.04 to 2.13 | 0.88 0.45 to 1.29 | 0.79 0.36 to 1.30 | 0.72 0.28 to 1.10 | 0.57 0.21 to 0.92 | 0.43 -0.62 to 1.52 | 0.42 -0.04 to 0.91 | 0.35 -0.70 to 1.46 | 0.27 -0.07 to 0.63 | 0.12 -0.14 to 0.38 | 0.01 -0.44 to 0.43 | ALBI_SC_FLEX_30-50_QW | -0.30 -0.77 to 0.20 |
| SEMA_PO_3MG_QD | -0.25 -0.64 to 0.20 | 2.01 1.49 to 2.46 | 1.89 1.37 to 2.33 | 1.79 1.42 to 2.16 | 1.64 1.12 to 2.11 | 1.57 0.63 to 2.56 | 1.54 1.16 to 1.91 | 1.36 0.41 to 2.37 | 1.18 0.70 to 1.63 | 1.10 0.79 to 1.42 | 1.02 0.46 to 1.50 | 0.88 0.47 to 1.25 | 0.73 -0.26 to 1.77 | 0.72 0.41 to 1.04 | 0.66 -0.35 to 1.69 | 0.58 0.22 to 0.91 | 0.43 -0.02 to 0.81 | 0.31 -0.14 to 0.72 | 0.30 -0.20 to 0.77 | 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.
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; 13 of 13 | Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 13 of 13 | Diabetes duration (years) effect modifier, prognostic factor; 12 of 13 | Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 12 of 13 | Age (years) prognostic factor; 13 of 13 | Treatment duration (weeks) effect modifier; 13 of 13 |
|---|---|---|---|---|---|---|
| AWARD-11 S000046 | 8.6 | S1 | 7.63 | 2.43 | 57.1 | 52 |
| NCT00838916 S000099 | 8.31 | S1 | 8.73 | 5.13 Asian subgroup rows | 55.43 | 156 |
| PIONEER 4 S000133 | 7.98 | S1 | 7.6 | 13.4 | 56.2 | 52 |
| PIONEER 10 S000234 | 8.31 | S1 | 9.36 | 100 | 58.43 | 52 |
| SUSTAIN™ 3 S000329 | 8.34 | S1 | 9.2 | not reported | 56.55 | 56 |
| ACHIEVE-3 S000438 | 8.29 | S1 | 8.7 | 11.9 | 53.93 | 52 |
| NCT04093752 S000909 | 8.71 | S1 | 7.63 | 97.27 | 54.13 | 40 |
| AWARD-2 S001130 | 8.14 | S1 | 9.1 | 16.91 | 56.66 | 78 |
| SUSTAIN FORTE S001353 | 8.9 | S1 | 9.5 | 7.18 | 58.05 | 40 |
| NCT05486065 S001555 | 8.35 | S1 | 6.96 | 1.49 | 52.76 | 40 |
| SURPASS-3 S001591 | 8.17 | S1 | 8.4 | 5.4 | 57.4 | 52 |
| SUSTAIN 8 S001847 | 8.25 | S1 | not reported | 15.86 | 56.6 | 52 |
| AWARD-1 S002153 | 8.07 | S1 | 8.77 | 2.45 | 55.65 | 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 8.0 (PLACEBO vs SEMA_PO_14MG_QD) to 8.9 (SEMA_SC_1p0MG_QW vs SEMA_SC_2p0MG_QW) percent; threshold 0.5
- FlagBaseline, Asian ancestry or region: design means range from 1.5 (PLACEBO vs SEMA_SC_2p0MG_QW) to 100.0 (DULA_SC_0p75MG_QW vs SEMA_PO_14MG_QD vs SEMA_PO_3MG_QD vs SEMA_PO_7MG_QD) percent Asian; threshold 30
- FlagBaseline, Treatment duration: design means range from 40.0 (INS_GLARGINE vs TIRZ_SC_10MG_QW vs TIRZ_SC_15MG_QW vs TIRZ_SC_5MG_QW) to 156.0 (ALBI_SC_FLEX_30-50_QW vs INS_GLARGINE) weeks; threshold 26
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 12, not stated 1
- NoteOutcome assessment, time point: selected time points span 40 to 56 weeks
- NoteOutcome assessment, analysis set: mixed: full_analysis 6, modified_itt 7
- NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 9, not stated 4
- NoteRisk of bias, blinding: mixed: double_blind 6, open_label 6, single_blind 1
| Trial | time weeks | analysis set | proportion method | definition | instrument | adjudicated | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AWARD-11 | 52 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2018 | age 18 or older; HbA1c 7.5 to 11.0%; BMI 25 or more; metformin 1500 mg/day or more; GLP-1 RA and insulin naive |
| NCT00838916 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | open_label | industry | 2009 | age 18 or older, HbA1c 7.0 to 10.0 percent, BMI 20 to 45, creatinine clearance above 60 |
| PIONEER 4 | 52 | 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 |
| PIONEER 10 | 52 | 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 |
| SUSTAIN™ 3 | 56 | full_analysis | not stated | not stated | not stated | 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 |
| ACHIEVE-3 | 52 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2023 | adults T2D on metformin; HbA1c 7.0 to 10.5 percent |
| NCT04093752 | 40 | modified_itt | not stated | not stated | not stated | not stated | hypothetical | hypothetical | open_label | industry | 2019 | adults with T2D on metformin with or without sulfonylurea |
| AWARD-2 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | open_label | industry | 2010 | type 2 diabetes on metformin and glimepiride |
| SUSTAIN FORTE | 40 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2019 | T2D on metformin with or without SU; HbA1c 8.0 to 10.0 percent; duration at least 6 months |
| NCT05486065 | 40 | full_analysis | not stated | not stated | not stated | not stated | hypothetical | hypothetical | double_blind | industry | 2022 | age 18 to 64; HbA1c 7.0 to 10.5; BMI 27 or more; on metformin |
| SURPASS-3 | 52 | 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 |
| 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 |
| AWARD-1 | 52 | 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 |
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 |
|---|---|---|---|---|---|---|---|---|---|
| AWARD-11 | A1 | DULA_SC_1p5MG_QW | 52 | contrast, md | R0022783:Figure 2 | ||||
| AWARD-11 | A3 | DULA_SC_4p5MG_QW | 52 | contrast, md | -0.310 | 0.061 | R0022783:Figure 2 | ||
| NCT00838916 | A1 | ALBI_SC_FLEX_30-50_QW | 52 | arm, change | -0.670 | 0.044 | 493 | registry:outcomes | |
| NCT00838916 | A2 | INS_GLARGINE | 52 | arm, change | -0.790 | 0.064 | 238 | registry:outcomes | |
| PIONEER 4 | A1 | SEMA_PO_14MG_QD | 52 | contrast, md | -1.400 | 0.102 | R0015836:Figure 2B | ||
| PIONEER 4 | A3 | PLACEBO | 52 | contrast, md | R0015836:Figure 2B | ||||
| PIONEER 10 | A1 | SEMA_PO_3MG_QD | 52 | arm, change | -0.700 | 0.100 | 102 | R0018421:Figure 2D | |
| PIONEER 10 | A2 | SEMA_PO_7MG_QD | 52 | arm, change | -1.400 | 0.100 | 114 | R0018421:Figure 2D | |
| PIONEER 10 | A3 | SEMA_PO_14MG_QD | 52 | arm, change | -1.800 | 0.100 | 113 | R0018421:Figure 2D | |
| PIONEER 10 | A4 | DULA_SC_0p75MG_QW | 52 | arm, change | -1.300 | 0.100 | 56 | R0018421:Figure 2D | |
| SUSTAIN™ 3 | A1 | SEMA_SC_1p0MG_QW | 56 | arm, change | -1.540 | 0.060 | 404 | registry:outcomes | |
| SUSTAIN™ 3 | A2 | EXENER_SC_2MG_QW | 56 | arm, change | -0.920 | 0.060 | 405 | registry:outcomes | |
| ACHIEVE-3 | A1 | ORFO_PO_12MG_QD | 52 | arm, change | -1.910 | 0.058 | 326 | registry:outcomes | |
| ACHIEVE-3 | A2 | ORFO_PO_36MG_QD | 52 | arm, change | -2.160 | 0.051 | 322 | registry:outcomes | |
| ACHIEVE-3 | A3 | SEMA_PO_7MG_QD | 52 | arm, change | -1.110 | 0.063 | 325 | registry:outcomes | |
| ACHIEVE-3 | A4 | SEMA_PO_14MG_QD | 52 | arm, change | -1.450 | 0.061 | 351 | registry:outcomes | |
| NCT04093752 | A1 | TIRZ_SC_5MG_QW | 40 | arm, change | -2.240 | 0.070 | 211 | registry:outcomes | |
| NCT04093752 | A2 | TIRZ_SC_10MG_QW | 40 | arm, change | -2.440 | 0.073 | 194 | registry:outcomes | |
| NCT04093752 | A3 | TIRZ_SC_15MG_QW | 40 | arm, change | -2.490 | 0.072 | 193 | registry:outcomes | |
| NCT04093752 | A4 | INS_GLARGINE | 40 | arm, change | -0.950 | 0.073 | 193 | registry:outcomes | |
| AWARD-2 | A1 | DULA_SC_1p5MG_QW | 52 | arm, change | -1.080 | 0.060 | 263 | registry:outcomes | |
| AWARD-2 | A2 | DULA_SC_0p75MG_QW | 52 | arm, change | -0.760 | 0.060 | 267 | registry:outcomes | |
| AWARD-2 | A3 | INS_GLARGINE | 52 | arm, change | -0.630 | 0.060 | 259 | registry:outcomes | |
| SUSTAIN FORTE | A1 | SEMA_SC_1p0MG_QW | 40 | arm, change | -2.000 | 0.046 | 481 | registry:outcomes | |
| SUSTAIN FORTE | A2 | SEMA_SC_2p0MG_QW | 40 | arm, change | -2.200 | 0.046 | 480 | registry:outcomes | |
| NCT05486065 | A1 | SEMA_SC_2p0MG_QW | 40 | contrast, md | -2.000 | 0.459 | R0005510:Figure 1 | ||
| NCT05486065 | A4 | PLACEBO | 40 | contrast, md | R0005510:Figure 1 | ||||
| SURPASS-3 | A1 | TIRZ_SC_5MG_QW | 52 | arm, change | -1.930 | 0.050 | 312 | R0007531:Table 2 | |
| SURPASS-3 | A2 | TIRZ_SC_10MG_QW | 52 | arm, change | -2.200 | 0.050 | 291 | R0007531:Table 2 | |
| SURPASS-3 | A3 | TIRZ_SC_15MG_QW | 52 | arm, change | -2.370 | 0.050 | 294 | R0007531:Table 2 | |
| SURPASS-3 | A4 | INS_DEGLUDEC | 52 | arm, change | -1.340 | 0.050 | 317 | R0007531:Table 2 | |
| SUSTAIN 8 | A1 | SEMA_SC_1p0MG_QW | 52 | arm, change | -1.700 | 0.055 | 394 | registry:outcomes | |
| SUSTAIN 8 | A2 | CANAGLIFLOZIN | 52 | arm, change | -1.000 | 0.050 | 394 | registry:outcomes | |
| AWARD-1 | A1 | DULA_SC_1p5MG_QW | 52 | arm, change | -1.360 | 0.080 | 271 | registry:outcomes | |
| AWARD-1 | A2 | DULA_SC_0p75MG_QW | 52 | arm, change | -1.070 | 0.080 | 269 | registry:outcomes | |
| AWARD-1 | A3 | EXEN_SC_10UG_BID | 52 | arm, change | -0.800 | 0.080 | 266 | registry:outcomes |
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