Network meta-analysis
HbA1c below 7 percent
Type 2 diabetes (adults); background therapy: one or more non insulin glucose lowering drugs
weeks 20 to 36 (target week 26)Not stated by the trialsEach dose separatelyOdds ratioSeparate part 2 of a disconnected network
16
Randomized trials
23
Treatments
8,883
Participants
4,294
Events
In plain language
Across 16 trials with 8,883 participants, 17 of 22 treatments had a clearly better result than placebo on HbA1c below 7 percent, and for 5 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide 1.0 mg subcutaneous once weekly: odds ratio 17.45 (95% credible interval 7.78 to 35.11).
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
Odds ratio. Higher values favor the treatment.
| Treatment | Bayesian OR (95% CrI) | 95% prediction interval | Frequentist OR (95% CI) | Verdict |
|---|---|---|---|---|
| Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW | 17.45 (7.78 to 35.11) | 5.41 to 47.85 | 19.68 (11.27 to 34.34) | Better |
| Insulin degludec and liraglutide (IDegLira) subcutaneous once daily titrated IDEGLIRA_SC_TIT_QD | 14.36 (3.11 to 37.96) | 2.54 to 47.66 | 18.04 (8.55 to 38.02) | Better |
| Polyethylene glycol loxenatide 400 µg injection once weekly PEGLOX_SC_400UG_QW | 10.27 (2.68 to 44.79) | 2.20 to 52.84 | 11.63 (3.21 to 42.08) | Better |
| IGlarLixi 2:1 pen subcutaneous once daily titrated IGLARLIXI2_SC_TIT_QD | 9.95 (2.94 to 22.15) | 2.30 to 28.92 | 11.79 (6.39 to 21.75) | Better |
| Dulaglutide 1.5 mg subcutaneous once weekly DULA_SC_1p5MG_QW | 9.20 (3.52 to 19.81) | 2.54 to 26.79 | 9.85 (5.49 to 17.67) | Better |
| Exenatide extended release and dapagliflozin 2 to 10 mg injection once weekly DAPAEXEN_SC_2-10MG_QW | 6.95 (1.51 to 20.14) | 1.24 to 24.24 | 9.47 (3.78 to 23.71) | Better |
| Dulaglutide 0.75 mg subcutaneous once weekly DULA_SC_0p75MG_QW | 6.80 (2.60 to 15.17) | 1.98 to 20.80 | 7.29 (4.10 to 12.97) | Better |
| Insulin glargine INS_GLARGINE | 5.07 (1.60 to 10.64) | 1.15 to 14.10 | 6.16 (3.36 to 11.29) | Better |
| Liraglutide 1.8 mg subcutaneous once daily LIRA_SC_1p8MG_QD | 4.73 (1.85 to 9.70) | 1.38 to 13.04 | 5.84 (3.12 to 10.92) | Better |
| Cotadutide 300 ug subcutaneous once daily COTA_SC_300UG_QD | 4.13 (1.65 to 9.27) | 1.19 to 12.26 | 4.40 (2.39 to 8.11) | Better |
| Cotadutide 200 ug subcutaneous once daily COTA_SC_200UG_QD | 3.88 (1.55 to 8.70) | 1.15 to 11.22 | 4.13 (2.25 to 7.61) | Better |
| Glimepiride GLIMEPIRIDE | 3.83 (1.48 to 8.45) | 1.05 to 11.06 | 4.50 (2.40 to 8.45) | Better |
| Liraglutide 1.2 mg subcutaneous once daily LIRA_SC_1p2MG_QD | 3.67 (1.64 to 7.32) | 1.15 to 9.99 | 4.24 (2.43 to 7.40) | Better |
| Exenatide extended release 2 mg subcutaneous once weekly EXENER_SC_2MG_QW | 3.28 (0.94 to 7.90) | 0.72 to 9.98 | 4.30 (2.01 to 9.17) | Unclear |
| Visepegenatide 150 µg injection once weekly VISEPE_SC_150UG_QW | 3.01 (1.28 to 6.93) | 0.99 to 9.14 | 3.07 (1.84 to 5.10) | Better |
| Cotadutide 100 ug subcutaneous once daily COTA_SC_100UG_QD | 3.00 (1.15 to 7.19) | 0.90 to 9.32 | 3.21 (1.62 to 6.35) | Better |
| Liraglutide 0.6 mg subcutaneous once daily LIRA_SC_0p6MG_QD | 2.62 (1.03 to 5.81) | 0.76 to 7.80 | 3.08 (1.63 to 5.82) | Better |
| Exenatide 10 ug subcutaneous twice daily EXEN_SC_10UG_BID | 2.46 (1.13 to 5.51) | 0.86 to 7.76 | 2.35 (1.23 to 4.48) | Better |
| Polyethylene glycol loxenatide 300 µg injection once weekly PEGLOX_SC_300UG_QW | 2.33 (0.69 to 7.47) | 0.56 to 9.19 | 2.54 (0.92 to 7.04) | Unclear |
| Dapagliflozin DAPAGLIFLOZIN | 2.02 (0.44 to 6.15) | 0.37 to 7.64 | 2.77 (1.08 to 7.08) | Unclear |
| Liraglutide 0.9 mg injection once daily LIRA_SC_0p9MG_QD | 1.95 (0.37 to 8.51) | 0.32 to 9.89 | 2.67 (0.70 to 10.26) | Unclear |
| Lixisenatide 20 ug subcutaneous once daily LIXI_SC_20UG_QD | 1.91 (0.95 to 3.14) | 0.65 to 4.75 | 2.07 (1.42 to 3.03) | Unclear |
Ranking
How likely each treatment is to be among the best. Rankings ignore the size of differences and their certainty, so read them with the effects above.
League table
Every treatment against every other: odds ratio 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_1p0MG_QW | IDEGLIRA_SC_TIT_QD | PEGLOX_SC_400UG_QW | IGLARLIXI2_SC_TIT_QD | DULA_SC_1p5MG_QW | DAPAEXEN_SC_2-10MG_QW | DULA_SC_0p75MG_QW | INS_GLARGINE | LIRA_SC_1p8MG_QD | COTA_SC_300UG_QD | COTA_SC_200UG_QD | GLIMEPIRIDE | LIRA_SC_1p2MG_QD | EXENER_SC_2MG_QW | VISEPE_SC_150UG_QW | COTA_SC_100UG_QD | LIRA_SC_0p6MG_QD | EXEN_SC_10UG_BID | PEGLOX_SC_300UG_QW | DAPAGLIFLOZIN | LIRA_SC_0p9MG_QD | LIXI_SC_20UG_QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 0.06 0.03 to 0.13 | 0.07 0.03 to 0.32 | 0.10 0.02 to 0.37 | 0.10 0.05 to 0.34 | 0.11 0.05 to 0.28 | 0.14 0.05 to 0.66 | 0.15 0.07 to 0.38 | 0.20 0.09 to 0.63 | 0.21 0.10 to 0.54 | 0.24 0.11 to 0.60 | 0.26 0.11 to 0.64 | 0.26 0.12 to 0.68 | 0.27 0.14 to 0.61 | 0.30 0.13 to 1.06 | 0.33 0.14 to 0.78 | 0.33 0.14 to 0.87 | 0.38 0.17 to 0.97 | 0.41 0.18 to 0.88 | 0.43 0.13 to 1.45 | 0.50 0.16 to 2.26 | 0.51 0.12 to 2.69 | 0.52 0.32 to 1.05 |
| SEMA_SC_1p0MG_QW | 17.45 7.78 to 35.11 | SEMA_SC_1p0MG_QW | 1.23 0.36 to 6.15 | 1.68 0.32 to 7.45 | 1.75 0.60 to 6.67 | 1.91 0.63 to 5.99 | 2.54 0.74 to 11.68 | 2.59 0.82 to 8.25 | 3.48 1.24 to 12.88 | 3.70 1.52 to 9.61 | 4.25 1.35 to 12.92 | 4.50 1.45 to 14.30 | 4.58 1.80 to 12.18 | 4.77 2.42 to 9.59 | 5.35 1.93 to 18.97 | 5.81 1.77 to 16.86 | 5.82 1.81 to 18.83 | 6.68 2.54 to 17.59 | 7.11 2.13 to 19.52 | 7.49 1.85 to 28.50 | 8.70 2.47 to 39.68 | 8.85 1.70 to 53.86 | 9.15 3.76 to 24.14 |
| IDEGLIRA_SC_TIT_QD | 14.36 3.11 to 37.96 | 0.82 0.16 to 2.78 | IDEGLIRA_SC_TIT_QD | 1.35 0.18 to 7.10 | 1.44 0.43 to 4.18 | 1.55 0.32 to 5.54 | 2.06 0.38 to 10.92 | 2.08 0.40 to 7.69 | 2.81 1.21 to 6.08 | 2.98 0.67 to 10.77 | 3.45 0.62 to 12.48 | 3.67 0.66 to 13.58 | 3.72 0.74 to 13.46 | 3.89 0.79 to 12.90 | 4.33 0.90 to 19.29 | 4.76 0.81 to 16.32 | 4.75 0.85 to 18.39 | 5.40 1.05 to 19.44 | 5.78 0.94 to 19.79 | 6.05 0.98 to 27.67 | 7.04 1.24 to 36.18 | 7.21 1.48 to 32.64 | 7.50 1.95 to 18.93 |
| PEGLOX_SC_400UG_QW | 10.27 2.68 to 44.79 | 0.60 0.13 to 3.09 | 0.74 0.14 to 5.59 | PEGLOX_SC_400UG_QW | 1.07 0.22 to 6.69 | 1.14 0.24 to 6.46 | 1.52 0.26 to 11.88 | 1.53 0.33 to 8.24 | 2.10 0.44 to 12.49 | 2.23 0.48 to 12.18 | 2.54 0.53 to 13.37 | 2.69 0.57 to 13.96 | 2.76 0.57 to 14.83 | 2.85 0.64 to 15.13 | 3.24 0.64 to 21.68 | 3.46 0.70 to 18.38 | 3.49 0.67 to 18.87 | 3.97 0.85 to 22.72 | 4.19 0.84 to 22.26 | 4.42 1.12 to 20.71 | 5.24 0.89 to 39.81 | 5.43 0.72 to 50.05 | 5.43 1.32 to 26.48 |
| IGLARLIXI2_SC_TIT_QD | 9.95 2.94 to 22.15 | 0.57 0.15 to 1.66 | 0.70 0.24 to 2.35 | 0.93 0.15 to 4.53 | IGLARLIXI2_SC_TIT_QD | 1.08 0.27 to 3.52 | 1.43 0.33 to 7.28 | 1.45 0.37 to 4.63 | 1.96 0.90 to 4.58 | 2.10 0.58 to 6.56 | 2.40 0.62 to 7.70 | 2.55 0.64 to 8.37 | 2.59 0.66 to 8.40 | 2.73 0.75 to 7.81 | 3.03 0.79 to 12.19 | 3.32 0.72 to 9.99 | 3.30 0.80 to 10.92 | 3.76 0.94 to 12.12 | 4.04 0.89 to 11.70 | 4.21 0.86 to 17.19 | 4.91 1.10 to 24.64 | 5.04 1.11 to 22.90 | 5.23 2.06 to 10.71 |
| DULA_SC_1p5MG_QW | 9.20 3.52 to 19.81 | 0.52 0.17 to 1.59 | 0.64 0.18 to 3.17 | 0.88 0.15 to 4.22 | 0.92 0.28 to 3.69 | DULA_SC_1p5MG_QW | 1.32 0.34 to 7.01 | 1.35 0.58 to 2.97 | 1.83 0.60 to 6.95 | 1.94 0.62 to 6.27 | 2.22 0.65 to 6.89 | 2.36 0.68 to 7.57 | 2.42 0.70 to 7.95 | 2.52 0.79 to 7.56 | 2.82 0.80 to 12.03 | 3.03 0.82 to 9.08 | 3.04 0.86 to 10.04 | 3.49 1.04 to 11.45 | 3.71 1.05 to 10.58 | 3.87 0.89 to 16.04 | 4.54 1.10 to 23.56 | 4.71 0.85 to 27.84 | 4.82 1.73 to 12.95 |
| DAPAEXEN_SC_2-10MG_QW | 6.95 1.51 to 20.14 | 0.39 0.09 to 1.36 | 0.49 0.09 to 2.66 | 0.66 0.08 to 3.79 | 0.70 0.14 to 3.07 | 0.76 0.14 to 2.93 | DAPAEXEN_SC_2-10MG_QW | 1.02 0.18 to 3.98 | 1.39 0.28 to 6.01 | 1.47 0.43 to 3.82 | 1.67 0.31 to 6.24 | 1.79 0.32 to 6.75 | 1.83 0.39 to 5.74 | 1.89 0.43 to 5.90 | 2.12 0.87 to 4.50 | 2.31 0.39 to 8.39 | 2.29 0.39 to 9.08 | 2.66 0.57 to 8.34 | 2.81 0.48 to 10.07 | 2.94 0.44 to 13.68 | 3.41 1.44 to 7.82 | 3.52 0.48 to 23.35 | 3.63 0.78 to 12.25 |
| DULA_SC_0p75MG_QW | 6.80 2.60 to 15.17 | 0.39 0.12 to 1.22 | 0.48 0.13 to 2.48 | 0.65 0.12 to 3.03 | 0.69 0.22 to 2.74 | 0.74 0.34 to 1.73 | 0.98 0.25 to 5.49 | DULA_SC_0p75MG_QW | 1.36 0.43 to 5.29 | 1.44 0.48 to 4.86 | 1.65 0.50 to 5.29 | 1.75 0.53 to 5.66 | 1.79 0.54 to 5.86 | 1.87 0.60 to 5.56 | 2.08 0.60 to 9.44 | 2.26 0.63 to 7.11 | 2.26 0.66 to 7.58 | 2.60 0.79 to 8.74 | 2.74 0.81 to 8.19 | 2.89 0.70 to 12.04 | 3.36 0.82 to 19.33 | 3.50 0.65 to 19.95 | 3.57 1.31 to 10.07 |
| INS_GLARGINE | 5.07 1.60 to 10.64 | 0.29 0.08 to 0.81 | 0.36 0.16 to 0.82 | 0.48 0.08 to 2.27 | 0.51 0.22 to 1.12 | 0.55 0.14 to 1.67 | 0.72 0.17 to 3.58 | 0.74 0.19 to 2.34 | INS_GLARGINE | 1.06 0.30 to 3.22 | 1.21 0.31 to 3.65 | 1.29 0.32 to 4.12 | 1.31 0.35 to 4.04 | 1.37 0.37 to 3.79 | 1.54 0.41 to 5.81 | 1.68 0.36 to 4.96 | 1.68 0.40 to 5.44 | 1.92 0.48 to 5.82 | 2.03 0.47 to 5.88 | 2.13 0.41 to 8.39 | 2.49 0.57 to 11.32 | 2.56 0.67 to 9.26 | 2.65 1.05 to 5.16 |
| LIRA_SC_1p8MG_QD | 4.73 1.85 to 9.70 | 0.27 0.10 to 0.66 | 0.34 0.09 to 1.50 | 0.45 0.08 to 2.09 | 0.48 0.15 to 1.73 | 0.52 0.16 to 1.62 | 0.68 0.26 to 2.33 | 0.70 0.21 to 2.10 | 0.94 0.31 to 3.30 | LIRA_SC_1p8MG_QD | 1.15 0.33 to 3.53 | 1.22 0.34 to 3.76 | 1.25 0.52 to 2.68 | 1.30 0.54 to 2.68 | 1.45 0.73 to 3.39 | 1.58 0.44 to 4.43 | 1.57 0.44 to 5.12 | 1.82 0.73 to 3.95 | 1.94 0.56 to 5.35 | 2.00 0.48 to 7.78 | 2.34 0.87 to 7.80 | 2.39 0.44 to 13.32 | 2.48 0.90 to 6.42 |
| COTA_SC_300UG_QD | 4.13 1.65 to 9.27 | 0.24 0.08 to 0.74 | 0.29 0.08 to 1.61 | 0.39 0.07 to 1.88 | 0.42 0.13 to 1.62 | 0.45 0.15 to 1.54 | 0.60 0.16 to 3.25 | 0.61 0.19 to 2.01 | 0.82 0.27 to 3.23 | 0.87 0.28 to 3.06 | COTA_SC_300UG_QD | 1.07 0.46 to 2.39 | 1.08 0.33 to 3.71 | 1.12 0.37 to 3.59 | 1.26 0.37 to 5.61 | 1.38 0.39 to 4.30 | 1.38 0.57 to 3.20 | 1.57 0.49 to 5.38 | 1.67 0.48 to 4.97 | 1.75 0.41 to 7.51 | 2.04 0.53 to 11.25 | 2.11 0.40 to 13.53 | 2.17 0.80 to 6.11 |
| COTA_SC_200UG_QD | 3.88 1.55 to 8.70 | 0.22 0.07 to 0.69 | 0.27 0.07 to 1.52 | 0.37 0.07 to 1.75 | 0.39 0.12 to 1.55 | 0.42 0.13 to 1.47 | 0.56 0.15 to 3.14 | 0.57 0.18 to 1.89 | 0.77 0.24 to 3.15 | 0.82 0.27 to 2.91 | 0.94 0.42 to 2.19 | COTA_SC_200UG_QD | 1.02 0.30 to 3.56 | 1.06 0.35 to 3.38 | 1.18 0.35 to 5.46 | 1.28 0.37 to 4.10 | 1.29 0.54 to 3.11 | 1.47 0.45 to 5.09 | 1.56 0.45 to 4.74 | 1.66 0.39 to 7.06 | 1.92 0.47 to 10.67 | 1.97 0.37 to 12.94 | 2.04 0.74 to 5.93 |
| GLIMEPIRIDE | 3.83 1.48 to 8.45 | 0.22 0.08 to 0.55 | 0.27 0.07 to 1.36 | 0.36 0.07 to 1.75 | 0.39 0.12 to 1.51 | 0.41 0.13 to 1.44 | 0.55 0.17 to 2.57 | 0.56 0.17 to 1.84 | 0.76 0.25 to 2.83 | 0.80 0.37 to 1.94 | 0.93 0.27 to 3.03 | 0.98 0.28 to 3.37 | GLIMEPIRIDE | 1.04 0.46 to 2.32 | 1.16 0.44 to 3.99 | 1.27 0.36 to 3.74 | 1.27 0.36 to 4.42 | 1.45 0.62 to 3.44 | 1.55 0.44 to 4.50 | 1.63 0.38 to 6.68 | 1.88 0.58 to 8.66 | 1.95 0.36 to 11.94 | 2.03 0.71 to 5.38 |
| LIRA_SC_1p2MG_QD | 3.67 1.64 to 7.32 | 0.21 0.10 to 0.41 | 0.26 0.08 to 1.26 | 0.35 0.07 to 1.56 | 0.37 0.13 to 1.34 | 0.40 0.13 to 1.26 | 0.53 0.17 to 2.33 | 0.54 0.18 to 1.66 | 0.73 0.26 to 2.71 | 0.77 0.37 to 1.84 | 0.89 0.28 to 2.68 | 0.94 0.30 to 2.89 | 0.96 0.43 to 2.18 | LIRA_SC_1p2MG_QD | 1.12 0.44 to 3.64 | 1.22 0.37 to 3.50 | 1.22 0.38 to 3.95 | 1.40 0.63 to 3.15 | 1.50 0.45 to 3.99 | 1.56 0.39 to 6.04 | 1.81 0.56 to 7.93 | 1.87 0.37 to 11.00 | 1.92 0.79 to 4.91 |
| EXENER_SC_2MG_QW | 3.28 0.94 to 7.90 | 0.19 0.05 to 0.52 | 0.23 0.05 to 1.11 | 0.31 0.05 to 1.56 | 0.33 0.08 to 1.27 | 0.35 0.08 to 1.24 | 0.47 0.22 to 1.15 | 0.48 0.11 to 1.66 | 0.65 0.17 to 2.41 | 0.69 0.30 to 1.37 | 0.79 0.18 to 2.71 | 0.85 0.18 to 2.86 | 0.86 0.25 to 2.25 | 0.89 0.27 to 2.28 | EXENER_SC_2MG_QW | 1.09 0.23 to 3.39 | 1.08 0.24 to 3.91 | 1.25 0.35 to 3.26 | 1.32 0.29 to 4.08 | 1.38 0.26 to 6.01 | 1.61 0.70 to 3.91 | 1.66 0.26 to 9.91 | 1.70 0.49 to 4.97 |
| VISEPE_SC_150UG_QW | 3.01 1.28 to 6.93 | 0.17 0.06 to 0.57 | 0.21 0.06 to 1.24 | 0.29 0.05 to 1.43 | 0.30 0.10 to 1.39 | 0.33 0.11 to 1.22 | 0.43 0.12 to 2.54 | 0.44 0.14 to 1.59 | 0.59 0.20 to 2.77 | 0.63 0.23 to 2.28 | 0.72 0.23 to 2.58 | 0.78 0.24 to 2.72 | 0.79 0.27 to 2.76 | 0.82 0.29 to 2.68 | 0.92 0.30 to 4.29 | VISEPE_SC_150UG_QW | 1.00 0.30 to 3.56 | 1.14 0.38 to 3.97 | 1.23 0.39 to 3.54 | 1.30 0.31 to 5.44 | 1.47 0.39 to 8.74 | 1.54 0.29 to 10.26 | 1.57 0.62 to 4.79 |
| COTA_SC_100UG_QD | 3.00 1.15 to 7.19 | 0.17 0.05 to 0.55 | 0.21 0.05 to 1.18 | 0.29 0.05 to 1.49 | 0.30 0.09 to 1.25 | 0.33 0.10 to 1.16 | 0.44 0.11 to 2.55 | 0.44 0.13 to 1.52 | 0.60 0.18 to 2.47 | 0.64 0.20 to 2.29 | 0.73 0.31 to 1.75 | 0.77 0.32 to 1.84 | 0.79 0.23 to 2.80 | 0.82 0.25 to 2.63 | 0.93 0.26 to 4.22 | 1.00 0.28 to 3.35 | COTA_SC_100UG_QD | 1.15 0.33 to 4.11 | 1.22 0.34 to 3.90 | 1.28 0.30 to 5.66 | 1.49 0.35 to 8.38 | 1.54 0.27 to 10.24 | 1.57 0.55 to 4.77 |
| LIRA_SC_0p6MG_QD | 2.62 1.03 to 5.81 | 0.15 0.06 to 0.39 | 0.19 0.05 to 0.95 | 0.25 0.04 to 1.18 | 0.27 0.08 to 1.07 | 0.29 0.09 to 0.96 | 0.38 0.12 to 1.76 | 0.38 0.11 to 1.27 | 0.52 0.17 to 2.11 | 0.55 0.25 to 1.37 | 0.64 0.19 to 2.03 | 0.68 0.20 to 2.24 | 0.69 0.29 to 1.60 | 0.72 0.32 to 1.59 | 0.80 0.31 to 2.82 | 0.87 0.25 to 2.62 | 0.87 0.24 to 3.05 | LIRA_SC_0p6MG_QD | 1.07 0.31 to 3.05 | 1.11 0.26 to 4.60 | 1.29 0.40 to 5.78 | 1.33 0.26 to 8.39 | 1.39 0.51 to 3.87 |
| EXEN_SC_10UG_BID | 2.46 1.13 to 5.51 | 0.14 0.05 to 0.47 | 0.17 0.05 to 1.06 | 0.24 0.04 to 1.19 | 0.25 0.09 to 1.12 | 0.27 0.09 to 0.95 | 0.36 0.10 to 2.06 | 0.36 0.12 to 1.23 | 0.49 0.17 to 2.15 | 0.52 0.19 to 1.77 | 0.60 0.20 to 2.10 | 0.64 0.21 to 2.24 | 0.64 0.22 to 2.30 | 0.67 0.25 to 2.20 | 0.76 0.24 to 3.40 | 0.81 0.28 to 2.57 | 0.82 0.26 to 2.98 | 0.94 0.33 to 3.27 | EXEN_SC_10UG_BID | 1.05 0.27 to 4.69 | 1.22 0.33 to 7.14 | 1.27 0.24 to 8.15 | 1.29 0.53 to 3.93 |
| PEGLOX_SC_300UG_QW | 2.33 0.69 to 7.47 | 0.13 0.04 to 0.54 | 0.17 0.04 to 1.02 | 0.23 0.05 to 0.89 | 0.24 0.06 to 1.16 | 0.26 0.06 to 1.12 | 0.34 0.07 to 2.28 | 0.35 0.08 to 1.44 | 0.47 0.12 to 2.46 | 0.50 0.13 to 2.10 | 0.57 0.13 to 2.43 | 0.60 0.14 to 2.58 | 0.62 0.15 to 2.63 | 0.64 0.17 to 2.58 | 0.73 0.17 to 3.80 | 0.77 0.18 to 3.26 | 0.78 0.18 to 3.35 | 0.90 0.22 to 3.85 | 0.96 0.21 to 3.67 | PEGLOX_SC_300UG_QW | 1.17 0.24 to 7.60 | 1.19 0.19 to 8.88 | 1.22 0.35 to 4.80 |
| DAPAGLIFLOZIN | 2.02 0.44 to 6.15 | 0.11 0.03 to 0.41 | 0.14 0.03 to 0.81 | 0.19 0.03 to 1.13 | 0.20 0.04 to 0.91 | 0.22 0.04 to 0.91 | 0.29 0.13 to 0.70 | 0.30 0.05 to 1.23 | 0.40 0.09 to 1.76 | 0.43 0.13 to 1.16 | 0.49 0.09 to 1.90 | 0.52 0.09 to 2.13 | 0.53 0.12 to 1.73 | 0.55 0.13 to 1.77 | 0.62 0.26 to 1.44 | 0.68 0.11 to 2.55 | 0.67 0.12 to 2.86 | 0.78 0.17 to 2.51 | 0.82 0.14 to 3.03 | 0.86 0.13 to 4.18 | DAPAGLIFLOZIN | 1.03 0.14 to 6.84 | 1.05 0.24 to 3.71 |
| LIRA_SC_0p9MG_QD | 1.95 0.37 to 8.51 | 0.11 0.02 to 0.59 | 0.14 0.03 to 0.67 | 0.18 0.02 to 1.38 | 0.20 0.04 to 0.90 | 0.21 0.04 to 1.17 | 0.28 0.04 to 2.09 | 0.29 0.05 to 1.55 | 0.39 0.11 to 1.49 | 0.42 0.08 to 2.25 | 0.47 0.07 to 2.51 | 0.51 0.08 to 2.74 | 0.51 0.08 to 2.78 | 0.54 0.09 to 2.68 | 0.60 0.10 to 3.77 | 0.65 0.10 to 3.46 | 0.65 0.10 to 3.65 | 0.75 0.12 to 3.88 | 0.79 0.12 to 4.11 | 0.84 0.11 to 5.33 | 0.97 0.15 to 7.10 | LIRA_SC_0p9MG_QD | 1.03 0.22 to 4.29 |
| LIXI_SC_20UG_QD | 1.91 0.95 to 3.14 | 0.11 0.04 to 0.27 | 0.13 0.05 to 0.51 | 0.18 0.04 to 0.76 | 0.19 0.09 to 0.48 | 0.21 0.08 to 0.58 | 0.28 0.08 to 1.28 | 0.28 0.10 to 0.77 | 0.38 0.19 to 0.96 | 0.40 0.16 to 1.11 | 0.46 0.16 to 1.25 | 0.49 0.17 to 1.34 | 0.49 0.19 to 1.41 | 0.52 0.20 to 1.27 | 0.59 0.20 to 2.06 | 0.64 0.21 to 1.62 | 0.64 0.21 to 1.82 | 0.72 0.26 to 1.96 | 0.77 0.25 to 1.89 | 0.82 0.21 to 2.88 | 0.95 0.27 to 4.23 | 0.97 0.23 to 4.64 | 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; 12 of 16 | Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 16 of 16 | Diabetes duration (years) effect modifier, prognostic factor; 11 of 16 |
|---|---|---|---|
| NCT03235050 S000257 | not reported | S1 | not reported |
| NCT01029886 S000352 | 8.45 | S1 | 8.49 |
| SUSTAIN 9 S000483 | 8.05 | S1 | 9.7 |
| SUSTAIN 10 S000584 | 8.2 | S1 | 9.3 |
| GETGOAL-F1 S001563 | 8.04 | S1 | 5.89 |
| NCT01149421 S000784 | 7.93 | S1 | 8.34 |
| NCT02229396 S000791 | 9.3 | S1 | 7.37 |
| DUAL™ VIII S001131 | not reported | S1 | not reported |
| GetGoal-M-Asia S001185 | 7.9 | S1 | 6.64 |
| NCT00701935 S001193 | not reported | S1 | not reported |
| LixiLan-O S001199 | 8.1 | S1 | 8.82 |
| NCT04504396 S001230 | 8.47 | S1 | 5.14 |
| LEAD-2 S001502 | 8.38 | S1 | 7.56 |
| NCT00603239 S001737 | not reported | S1 | not reported |
| S002928 S002928 | 7.3 median | S1 | not reported |
| S003006 S003006 | 8.25 | S1 | 12.45 |
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: not reported by 4 of 16 trials
- FlagBaseline, Baseline HbA1c: design means range from 7.3 (PEGLOX_SC_300UG_QW vs PEGLOX_SC_400UG_QW vs PLACEBO) to 9.3 (DAPAEXEN_SC_2-10MG_QW vs DAPAGLIFLOZIN vs EXENER_SC_2MG_QW) percent; threshold 0.5
- FlagBaseline, Diabetes duration: not reported by 5 of 16 trials
- FlagBaseline, Diabetes duration: design means range from 5.1 (PLACEBO vs VISEPE_SC_150UG_QW) to 12.4 (INS_GLARGINE vs LIRA_SC_0p9MG_QD) years; threshold 3
- FlagEligibility, bmi entry range: a design requires bmi 50 or more while another admits only 40 or less
- NoteOutcome assessment, time point: selected time points span 24 to 30 weeks
- NoteOutcome assessment, analysis set: mixed: completers 3, full_analysis 5, modified_itt 8
- NoteOutcome assessment, definition: mixed: HbA1c 7 percent or less 1, HbA1c 7.0 percent or lower 1, HbA1c at or below 7 percent 1, HbA1c below 7 percent 1, HbA1c below 7 percent at week 24 1, HbA1c below 7 percent at week 28 1, not stated 10
- NoteOutcome assessment, proportion method: mixed: not stated 5, not_stated 5, observed 6
- NoteRisk of bias, blinding: mixed: double_blind 10, open_label 5, single_blind 1
- NoteRisk of bias, funding: mixed: industry 14, non_industry 2
- NoteData handling, input conversions: arms_combined 1, count_from_percent 26
| Trial | definition | time weeks | analysis set | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03235050 | not stated | 26 | full_analysis | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | age 18 or older; BMI 25 or higher; HbA1c 7.0 to 10.5 percent; on metformin |
| NCT01029886 | HbA1c below 7 percent | 26 | modified_itt | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2010 | adults 18 or older with type 2 diabetes on oral agents, HbA1c 7.1 to 11.0 percent, BMI 45 or less |
| SUSTAIN 9 | not stated | 30 | full_analysis | not stated | not stated | observed | 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 |
| SUSTAIN 10 | not stated | 30 | full_analysis | not stated | not stated | not_stated | not stated | not stated | open_label | industry | 2017 | adults with T2D, HbA1c 7.0 to 11.0 percent on 1 to 3 oral drugs |
| GETGOAL-F1 | not stated | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2008 | adults with T2D on metformin |
| NCT01149421 | not stated | 26 | modified_itt | not stated | not stated | observed | not stated | not stated | double_blind | industry | 2010 | adults 18 or older; HbA1c 7 to 9.5 percent; stable oral agents |
| NCT02229396 | HbA1c below 7 percent at week 28 | 28 | modified_itt | not stated | not stated | not_stated | not stated | not stated | double_blind | industry | 2014 | age 18 or older; HbA1c 8.0 to 12.0 percent on metformin 1500 mg/d or more |
| DUAL™ VIII | not stated | 26 | full_analysis | not stated | not stated | observed | not stated | not stated | open_label | industry | 2016 | adults with type 2 diabetes uncontrolled on oral drugs, insulin naive |
| GetGoal-M-Asia | HbA1c at or below 7 percent | 24 | modified_itt | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2010 | Asian adults with type 2 diabetes on metformin with or without sulfonylurea |
| NCT00701935 | HbA1c 7.0 percent or lower | 26.07 | completers | not stated | not stated | observed | not stated | not stated | double_blind | industry | 2008 | adults with T2D on metformin |
| LixiLan-O | not stated | 30 | modified_itt | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2014 | adults; HbA1c 7.5 to 10% on metformin or 7 to 9% on metformin plus second OAD; 7 to 10% after run in |
| NCT04504396 | not stated | 24 | full_analysis | not stated | not stated | observed | not stated | not stated | 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 |
| LEAD-2 | not stated | 26 | modified_itt | not stated | not stated | not_stated | not stated | not stated | double_blind | industry | 2006 | age 18 to 80; HbA1c 7 to 11 percent on one OAD or 7 to 10 on combination; BMI 40 or less; no recent insulin |
| NCT00603239 | HbA1c 7 percent or less | 26 | modified_itt | not stated | not stated | not_stated | not stated | not stated | double_blind | industry | 2008 | type 2 diabetes on a thiazolidinedione with or without metformin |
| S002928 | HbA1c below 7 percent at week 24 | 24 | completers | not stated | not stated | not_stated | not stated | not stated | single_blind | non_industry | 2022 | age 18 to 65; BMI 50 or more; type 2 diabetes |
| S003006 | not stated | 24 | completers | not stated | not stated | observed | not stated | not stated | open_label | non_industry | 2013 | Japanese adults 20 or older; HbA1c 7.0 to below 10 on DPP-4 inhibitor based oral therapy |
Trial data
What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the odds ratio on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.
| Trial | Arm | Treatment | Week | Data | Value | SE | Events / N | Flags | Source |
|---|---|---|---|---|---|---|---|---|---|
| NCT03235050 | A1 | PLACEBO | 26 | arm, responders | 25 / 112 | registry:outcomes | |||
| NCT03235050 | A3 | COTA_SC_100UG_QD | 26 | arm, responders | 48 / 100 | registry:outcomes | |||
| NCT03235050 | A4 | COTA_SC_200UG_QD | 26 | arm, responders | 139 / 256 | registry:outcomes | |||
| NCT03235050 | A5 | COTA_SC_300UG_QD | 26 | arm, responders | 143 / 256 | registry:outcomes | |||
| NCT01029886 | A1 | EXENER_SC_2MG_QW | 26 | arm, responders | 243 / 461 | R0016299:Results | |||
| NCT01029886 | A2 | LIRA_SC_1p8MG_QD | 26 | arm, responders | 271 / 450 | R0016299:Results | |||
| SUSTAIN 9 | A1 | SEMA_SC_1p0MG_QW | 30 | arm, responders | 99 / 120 | count_from_percent | registry:outcomes | ||
| SUSTAIN 9 | A2 | PLACEBO | 30 | arm, responders | 26 / 127 | count_from_percent | registry:outcomes | ||
| SUSTAIN 10 | A1 | SEMA_SC_1p0MG_QW | 30 | arm, responders | 233 / 290 | count_from_percent | registry:outcomes | ||
| SUSTAIN 10 | A2 | LIRA_SC_1p2MG_QD | 30 | arm, responders | 132 / 287 | count_from_percent | registry:outcomes | ||
| NCT01149421 | A1 | DULA_SC_1p5MG_QW | 26 | arm, responders | 128 / 206 | count_from_percent | registry:outcomes | ||
| NCT01149421 | A2 | DULA_SC_0p75MG_QW | 26 | arm, responders | 124 / 226 | count_from_percent | registry:outcomes | ||
| NCT01149421 | A3 | PLACEBO | 26 | arm, responders | 30 / 210 | count_from_percent | registry:outcomes | ||
| NCT02229396 | A1 | DAPAEXEN_SC_2-10MG_QW | 28 | arm, responders | 102 / 228 | count_from_percent | registry:outcomes | ||
| NCT02229396 | A2 | EXENER_SC_2MG_QW | 28 | arm, responders | 61 / 227 | count_from_percent | registry:outcomes | ||
| NCT02229396 | A3 | DAPAGLIFLOZIN | 28 | arm, responders | 44 / 230 | count_from_percent | registry:outcomes | ||
| DUAL™ VIII | A1 | IDEGLIRA_SC_TIT_QD | 26 | arm, responders | 398 / 506 | count_from_percent | registry:outcomes | ||
| DUAL™ VIII | A2 | INS_GLARGINE | 26 | arm, responders | 282 / 506 | count_from_percent | registry:outcomes | ||
| GetGoal-M-Asia | A1 | PLACEBO | 24 | arm, responders | 84 / 188 | R0021439:Table 5 | |||
| GetGoal-M-Asia | A2 | LIXI_SC_20UG_QD | 24 | arm, responders | 107 / 185 | R0021439:Table 5 | |||
| NCT00701935 | A1 | EXEN_SC_10UG_BID | 26.07 | arm, responders | 17 / 28 | count_from_percent | registry:outcomes | ||
| NCT00701935 | A2 | PLACEBO | 26.07 | arm, responders | 6 / 28 | count_from_percent | registry:outcomes | ||
| LixiLan-O | A1 | IGLARLIXI2_SC_TIT_QD | 30 | arm, responders | 345 / 468 | R0013783:Supplement Table S2 | |||
| LixiLan-O | A2 | INS_GLARGINE | 30 | arm, responders | 277 / 466 | R0013783:Supplement Table S2 | |||
| LixiLan-O | A3 | LIXI_SC_20UG_QD | 30 | arm, responders | 77 / 233 | R0013783:Supplement Table S2 | |||
| NCT04504396 | A1 | VISEPE_SC_150UG_QW | 24 | arm, responders | 115 / 310 | R0009432:Table 2 | |||
| NCT04504396 | A2 | PLACEBO | 24 | arm, responders | 50 / 310 | R0009432:Table 2 | |||
| LEAD-2 | A1 | LIRA_SC_0p6MG_QD | 26 | arm, responders | 68 / 242 | count_from_percent | R0019848:Figure 1E | ||
| LEAD-2 | A2 | LIRA_SC_1p2MG_QD | 26 | arm, responders | 85 / 240 | count_from_percent | R0019848:Figure 1E | ||
| LEAD-2 | A3 | LIRA_SC_1p8MG_QD | 26 | arm, responders | 103 / 242 | count_from_percent | R0019848:Figure 1E | ||
| LEAD-2 | A4 | GLIMEPIRIDE | 26 | arm, responders | 88 / 242 | count_from_percent | R0019848:Figure 1E | ||
| LEAD-2 | A5 | PLACEBO | 26 | arm, responders | 13 / 121 | count_from_percent | R0019848:Figure 1E | ||
| GETGOAL-F1 | A1 | PLACEBO | 24 | arm, responders | 38 / 158 | R0021439:Supplement Table 2 | |||
| GETGOAL-F1 | A2+A3 | LIXI_SC_20UG_QD | 24 | arm, responders | 138 / 308 | arms_combined | R0021439:Supplement Table 2 | ||
| NCT00603239 | A1 | EXEN_SC_10UG_BID | 26 | arm, responders | 51 / 104 | count_from_percent | registry:outcomes | ||
| NCT00603239 | A2 | PLACEBO | 26 | arm, responders | 19 / 52 | count_from_percent | registry:outcomes | ||
| S002928 | A1 | PLACEBO | 24 | arm, responders | 14 / 35 | count_from_percent | R0007034:Results | ||
| S002928 | A2 | PEGLOX_SC_300UG_QW | 24 | arm, responders | 22 / 35 | count_from_percent | R0007034:Results | ||
| S002928 | A3 | PEGLOX_SC_400UG_QW | 24 | arm, responders | 31 / 35 | count_from_percent | R0007034:Results | ||
| S003006 | A1 | INS_GLARGINE | 24 | arm, responders | 11 / 26 | count_from_percent | R0010916:Results | ||
| S003006 | A2 | LIRA_SC_0p9MG_QD | 24 | arm, responders | 7 / 29 | count_from_percent | R0010916:Results |
Rerun this analysis yourself
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