Network meta-analysis
Systolic blood pressure change
Type 2 diabetes (adults)
weeks 36 to 64 (target week 52)Not stated by the trialsDoses of a drug pooledMean difference
27
Randomized trials
22
Treatments
16,031
Participants
59
Trial arms
In plain language
Across 27 trials with 16,031 participants, 0 of 21 treatments had a clearly better result than placebo on systolic blood pressure change, 1 a clearly worse one, and for 20 the evidence could not tell them apart from placebo. The most favorable estimate was for Empagliflozin: mean difference -5.73 mmHg (95% credible interval -13.94 to 2.72).
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 mmHg. Lower values favor the treatment.
| Treatment | Bayesian MD (95% CrI) | 95% prediction interval | Frequentist MD (95% CI) | Verdict |
|---|---|---|---|---|
| Empagliflozin EMPAGLIFLOZIN | -5.73 (-13.94 to 2.72) | -14.50 to 3.84 | -6.31 (-14.32 to 1.70) | Unclear |
| Liraglutide and empagliflozin injection EMPALIRA_SC | -3.85 (-11.66 to 4.56) | -12.54 to 5.57 | -4.31 (-12.14 to 3.52) | Unclear |
| Canagliflozin CANAGLIFLOZIN | -3.23 (-9.27 to 3.93) | -10.46 to 5.14 | -3.30 (-9.20 to 2.61) | Unclear |
| Tirzepatide injection TIRZ_SC | -3.18 (-8.14 to 1.74) | -9.59 to 3.39 | -3.10 (-7.76 to 1.56) | Unclear |
| Basal insulin OTHER_ACTIVE_basal_insulin | -1.84 (-9.81 to 6.57) | -10.63 to 7.60 | -2.31 (-10.32 to 5.70) | Unclear |
| Semaglutide tablet SEMA_PO | -1.39 (-4.20 to 1.86) | -6.12 to 3.77 | -1.40 (-4.19 to 1.39) | Unclear |
| Liraglutide injection LIRA_SC | -1.20 (-4.06 to 2.39) | -5.93 to 4.60 | -1.31 (-4.33 to 1.71) | Unclear |
| Semaglutide injection SEMA_SC | -1.10 (-5.41 to 4.37) | -6.85 to 6.01 | -1.20 (-5.61 to 3.21) | Unclear |
| Exenatide injection EXEN_SC | -0.05 (-4.56 to 6.09) | -5.81 to 7.49 | -0.20 (-5.07 to 4.68) | Unclear |
| Taspoglutide injection TASP_SC | 0.01 (-4.91 to 5.75) | -6.07 to 7.16 | -0.14 (-4.97 to 4.68) | Unclear |
| Sitagliptin SITAGLIPTIN | 0.79 (-2.68 to 5.05) | -4.36 to 6.78 | 0.71 (-2.88 to 4.30) | Unclear |
| Premixed insulin INS_PREMIX | 1.04 (-4.24 to 8.51) | -5.44 to 9.80 | 1.02 (-4.84 to 6.89) | Unclear |
| Dulaglutide injection DULA_SC | 1.16 (-2.67 to 6.60) | -3.98 to 8.20 | 1.07 (-3.08 to 5.22) | Unclear |
| Pioglitazone PIOGLITAZONE | 1.49 (-4.27 to 8.79) | -5.31 to 9.92 | 1.41 (-4.54 to 7.36) | Unclear |
| Metformin METFORMIN | 1.56 (-4.04 to 8.82) | -5.05 to 9.83 | 1.51 (-4.28 to 7.29) | Unclear |
| Insulin glargine INS_GLARGINE | 2.19 (-2.28 to 8.19) | -3.51 to 9.70 | 2.10 (-2.64 to 6.83) | Unclear |
| Insulin degludec with liraglutide injection IDEGLIRA_SC | 2.29 (-2.64 to 8.31) | -3.99 to 9.64 | 2.19 (-2.84 to 7.22) | Unclear |
| Insulin aspart (prandial) INS_ASPART | 2.61 (-2.96 to 9.86) | -4.25 to 10.95 | 2.60 (-3.15 to 8.35) | Unclear |
| Insulin lispro (prandial) INS_LISPRO | 3.90 (-2.76 to 10.37) | -3.94 to 11.44 | 3.94 (-1.99 to 9.86) | Unclear |
| Insulin degludec INS_DEGLUDEC | 3.95 (-1.12 to 10.04) | -2.42 to 11.46 | 3.89 (-1.23 to 9.01) | Unclear |
| Standard care or no added treatment STANDARD_CARE | 6.12 (0.11 to 13.30) | -0.72 to 14.40 | 5.78 (-0.24 to 11.81) | Worse |
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 | EMPAGLIFLOZIN | EMPALIRA_SC | CANAGLIFLOZIN | TIRZ_SC | OTHER_ACTIVE_basal_insulin | SEMA_PO | LIRA_SC | SEMA_SC | EXEN_SC | TASP_SC | SITAGLIPTIN | INS_PREMIX | DULA_SC | PIOGLITAZONE | METFORMIN | INS_GLARGINE | IDEGLIRA_SC | INS_ASPART | INS_LISPRO | INS_DEGLUDEC | STANDARD_CARE |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO | PLACEBO | 5.73 -2.72 to 13.94 | 3.85 -4.56 to 11.66 | 3.23 -3.93 to 9.27 | 3.18 -1.74 to 8.14 | 1.84 -6.57 to 9.81 | 1.39 -1.86 to 4.20 | 1.20 -2.39 to 4.06 | 1.10 -4.37 to 5.41 | 0.05 -6.09 to 4.56 | -0.01 -5.75 to 4.91 | -0.79 -5.05 to 2.68 | -1.04 -8.51 to 4.24 | -1.16 -6.60 to 2.67 | -1.49 -8.79 to 4.27 | -1.56 -8.82 to 4.04 | -2.19 -8.19 to 2.28 | -2.29 -8.31 to 2.64 | -2.61 -9.86 to 2.96 | -3.90 -10.37 to 2.76 | -3.95 -10.04 to 1.12 | -6.12 -13.30 to -0.11 |
| EMPAGLIFLOZIN | -5.73 -13.94 to 2.72 | EMPAGLIFLOZIN | -2.01 -9.26 to 5.29 | -2.61 -12.50 to 7.23 | -2.59 -12.04 to 7.14 | -3.86 -11.64 to 3.59 | -4.40 -12.70 to 4.28 | -4.57 -12.30 to 3.08 | -4.69 -13.45 to 3.80 | -5.81 -14.87 to 2.96 | -5.77 -14.84 to 3.19 | -6.60 -15.00 to 1.82 | -6.97 -16.79 to 2.17 | -7.00 -15.54 to 1.10 | -7.38 -17.28 to 2.00 | -7.40 -17.30 to 1.86 | -8.02 -16.92 to 0.40 | -8.16 -16.87 to 0.84 | -8.52 -18.09 to 0.92 | -9.70 -19.73 to 1.39 | -9.77 -18.53 to -0.89 | -11.90 -21.59 to -2.49 |
| EMPALIRA_SC | -3.85 -11.66 to 4.56 | 2.01 -5.29 to 9.26 | EMPALIRA_SC | -0.69 -10.16 to 9.03 | -0.65 -9.82 to 9.46 | -1.90 -9.37 to 5.44 | -2.47 -10.57 to 6.20 | -2.70 -9.88 to 4.95 | -2.83 -11.19 to 5.89 | -3.92 -12.82 to 4.60 | -3.88 -12.76 to 5.04 | -4.74 -12.84 to 3.64 | -5.03 -14.90 to 4.01 | -5.10 -13.35 to 3.19 | -5.45 -15.24 to 3.72 | -5.52 -14.84 to 3.88 | -6.09 -14.70 to 2.27 | -6.25 -14.67 to 2.72 | -6.62 -15.95 to 3.08 | -7.76 -17.60 to 3.26 | -7.85 -16.44 to 1.08 | -9.99 -19.62 to -0.60 |
| CANAGLIFLOZIN | -3.23 -9.27 to 3.93 | 2.61 -7.23 to 12.50 | 0.69 -9.03 to 10.16 | CANAGLIFLOZIN | -0.02 -7.68 to 8.99 | -1.31 -11.02 to 8.42 | -1.82 -8.19 to 5.02 | -1.96 -8.03 to 4.21 | -2.11 -6.54 to 2.35 | -3.19 -9.90 to 3.03 | -3.21 -9.82 to 3.36 | -4.01 -9.58 to 1.89 | -4.24 -12.37 to 2.60 | -4.31 -10.33 to 1.05 | -4.72 -12.49 to 2.26 | -4.79 -12.44 to 2.06 | -5.35 -11.89 to 0.64 | -5.49 -12.93 to 1.81 | -5.89 -11.90 to 0.31 | -7.07 -15.65 to 2.74 | -7.22 -14.81 to 0.40 | -9.27 -17.00 to -2.45 |
| TIRZ_SC | -3.18 -8.14 to 1.74 | 2.59 -7.14 to 12.04 | 0.65 -9.46 to 9.82 | 0.02 -8.99 to 7.68 | TIRZ_SC | -1.31 -11.26 to 8.13 | -1.79 -7.92 to 3.86 | -1.94 -8.39 to 3.70 | -2.04 -9.52 to 4.44 | -3.22 -11.01 to 3.40 | -3.20 -10.97 to 3.66 | -3.96 -10.76 to 1.88 | -4.27 -13.28 to 2.91 | -4.30 -12.01 to 1.61 | -4.69 -13.71 to 2.75 | -4.75 -13.87 to 2.49 | -5.37 -13.40 to 0.94 | -5.52 -13.29 to 1.37 | -5.84 -14.41 to 1.54 | -7.04 -11.38 to -2.70 | -7.16 -15.11 to 0.10 | -9.30 -18.28 to -1.62 |
| OTHER_ACTIVE_basal_insulin | -1.84 -9.81 to 6.57 | 3.86 -3.59 to 11.64 | 1.90 -5.44 to 9.37 | 1.31 -8.42 to 11.02 | 1.31 -8.13 to 11.26 | OTHER_ACTIVE_basal_insulin | -0.50 -8.66 to 8.05 | -0.67 -8.24 to 6.84 | -0.83 -9.45 to 7.81 | -1.87 -10.91 to 6.81 | -1.91 -10.83 to 7.09 | -2.71 -10.92 to 5.61 | -3.02 -12.91 to 5.97 | -3.08 -11.48 to 5.09 | -3.41 -13.32 to 5.75 | -3.54 -13.13 to 5.87 | -4.12 -12.84 to 4.34 | -4.21 -12.87 to 4.55 | -4.53 -14.22 to 4.87 | -5.79 -15.94 to 5.36 | -5.86 -14.58 to 2.99 | -7.98 -17.77 to 1.11 |
| SEMA_PO | -1.39 -4.20 to 1.86 | 4.40 -4.28 to 12.70 | 2.47 -6.20 to 10.57 | 1.82 -5.02 to 8.19 | 1.79 -3.86 to 7.92 | 0.50 -8.05 to 8.66 | SEMA_PO | -0.16 -4.03 to 3.18 | -0.26 -5.43 to 4.24 | -1.35 -7.13 to 3.34 | -1.35 -6.94 to 3.55 | -2.17 -6.05 to 1.19 | -2.44 -9.64 to 3.06 | -2.54 -7.96 to 1.50 | -2.87 -10.10 to 2.97 | -2.95 -10.19 to 2.89 | -3.55 -9.63 to 1.09 | -3.68 -9.83 to 1.62 | -4.02 -10.82 to 1.74 | -5.28 -12.18 to 2.05 | -5.35 -11.50 to 0.15 | -7.48 -14.64 to -1.36 |
| LIRA_SC | -1.20 -4.06 to 2.39 | 4.57 -3.08 to 12.30 | 2.70 -4.95 to 9.88 | 1.96 -4.21 to 8.03 | 1.94 -3.70 to 8.39 | 0.67 -6.84 to 8.24 | 0.16 -3.18 to 4.03 | LIRA_SC | -0.11 -4.43 to 3.97 | -1.19 -6.13 to 3.10 | -1.19 -6.08 to 3.55 | -2.04 -5.16 to 1.13 | -2.24 -8.66 to 2.86 | -2.38 -6.30 to 0.79 | -2.71 -9.13 to 2.60 | -2.81 -9.05 to 2.58 | -3.39 -8.02 to 0.47 | -3.54 -7.97 to 0.95 | -3.88 -9.86 to 2.00 | -5.10 -11.84 to 2.67 | -5.20 -9.75 to -0.56 | -7.27 -13.51 to -1.89 |
| SEMA_SC | -1.10 -5.41 to 4.37 | 4.69 -3.80 to 13.45 | 2.83 -5.89 to 11.19 | 2.11 -2.35 to 6.54 | 2.04 -4.44 to 9.52 | 0.83 -7.81 to 9.45 | 0.26 -4.24 to 5.43 | 0.11 -3.97 to 4.43 | SEMA_SC | -1.08 -5.92 to 3.31 | -1.10 -5.96 to 3.78 | -1.94 -5.26 to 1.85 | -2.16 -8.61 to 3.15 | -2.23 -6.13 to 1.00 | -2.60 -8.99 to 2.96 | -2.69 -8.81 to 2.86 | -3.25 -8.04 to 0.88 | -3.45 -9.36 to 2.65 | -3.75 -8.02 to 0.29 | -4.94 -12.43 to 3.66 | -5.08 -11.03 to 1.11 | -7.18 -13.43 to -1.62 |
| EXEN_SC | -0.05 -4.56 to 6.09 | 5.81 -2.96 to 14.87 | 3.92 -4.60 to 12.82 | 3.19 -3.03 to 9.90 | 3.22 -3.40 to 11.01 | 1.87 -6.81 to 10.91 | 1.35 -3.34 to 7.13 | 1.19 -3.10 to 6.13 | 1.08 -3.31 to 5.92 | EXEN_SC | -0.01 -3.90 to 4.25 | -0.83 -4.81 to 3.79 | -1.07 -5.07 to 2.26 | -1.17 -4.83 to 2.31 | -1.53 -5.53 to 2.36 | -1.59 -7.61 to 3.96 | -2.19 -6.73 to 2.07 | -2.32 -8.47 to 4.27 | -2.70 -8.65 to 3.63 | -3.90 -11.53 to 5.20 | -3.97 -10.23 to 2.77 | -6.06 -11.36 to -1.09 |
| TASP_SC | 0.01 -4.91 to 5.75 | 5.77 -3.19 to 14.84 | 3.88 -5.04 to 12.76 | 3.21 -3.36 to 9.82 | 3.20 -3.66 to 10.97 | 1.91 -7.09 to 10.83 | 1.35 -3.55 to 6.94 | 1.19 -3.55 to 6.08 | 1.10 -3.78 to 5.96 | 0.01 -4.25 to 3.90 | TASP_SC | -0.83 -4.63 to 3.20 | -1.11 -6.96 to 3.84 | -1.17 -5.95 to 3.05 | -1.54 -7.48 to 3.75 | -1.56 -8.36 to 4.43 | -2.19 -7.70 to 2.62 | -2.30 -8.82 to 4.16 | -2.70 -9.12 to 3.58 | -3.89 -11.67 to 5.03 | -3.94 -10.54 to 2.75 | -6.08 -12.62 to -0.34 |
| SITAGLIPTIN | 0.79 -2.68 to 5.05 | 6.60 -1.82 to 15.00 | 4.74 -3.64 to 12.84 | 4.01 -1.89 to 9.58 | 3.96 -1.88 to 10.76 | 2.71 -5.61 to 10.92 | 2.17 -1.19 to 6.05 | 2.04 -1.13 to 5.16 | 1.94 -1.85 to 5.26 | 0.83 -3.79 to 4.81 | 0.83 -3.20 to 4.63 | SITAGLIPTIN | -0.25 -6.55 to 4.62 | -0.33 -4.47 to 2.83 | -0.65 -6.92 to 4.43 | -0.75 -7.15 to 4.67 | -1.37 -6.18 to 2.56 | -1.49 -7.11 to 3.80 | -1.85 -7.60 to 3.38 | -3.12 -10.08 to 4.96 | -3.16 -8.75 to 2.39 | -5.28 -11.54 to 0.20 |
| INS_PREMIX | 1.04 -4.24 to 8.51 | 6.97 -2.17 to 16.79 | 5.03 -4.01 to 14.90 | 4.24 -2.60 to 12.37 | 4.27 -2.91 to 13.28 | 3.02 -5.97 to 12.91 | 2.44 -3.06 to 9.64 | 2.24 -2.86 to 8.66 | 2.16 -3.15 to 8.61 | 1.07 -2.26 to 5.07 | 1.11 -3.84 to 6.96 | 0.25 -4.62 to 6.55 | INS_PREMIX | -0.09 -5.05 to 5.14 | -0.47 -4.19 to 3.70 | -0.48 -7.32 to 6.40 | -1.10 -6.56 to 4.78 | -1.20 -7.92 to 6.60 | -1.63 -8.16 to 5.95 | -2.78 -10.82 to 7.50 | -2.87 -9.58 to 4.65 | -4.90 -11.29 to 1.23 |
| DULA_SC | 1.16 -2.67 to 6.60 | 7.00 -1.10 to 15.54 | 5.10 -3.19 to 13.35 | 4.31 -1.05 to 10.33 | 4.30 -1.61 to 12.01 | 3.08 -5.09 to 11.48 | 2.54 -1.50 to 7.96 | 2.38 -0.79 to 6.30 | 2.23 -1.00 to 6.13 | 1.17 -2.31 to 4.83 | 1.17 -3.05 to 5.95 | 0.33 -2.83 to 4.47 | 0.09 -5.14 to 5.05 | DULA_SC | -0.37 -5.55 to 4.78 | -0.43 -5.09 to 4.18 | -1.04 -3.61 to 1.58 | -1.16 -6.42 to 4.76 | -1.53 -6.73 to 4.16 | -2.74 -9.78 to 6.24 | -2.82 -8.22 to 3.33 | -4.87 -9.95 to -0.02 |
| PIOGLITAZONE | 1.49 -4.27 to 8.79 | 7.38 -2.00 to 17.28 | 5.45 -3.72 to 15.24 | 4.72 -2.26 to 12.49 | 4.69 -2.75 to 13.71 | 3.41 -5.75 to 13.32 | 2.87 -2.97 to 10.10 | 2.71 -2.60 to 9.13 | 2.60 -2.96 to 8.99 | 1.53 -2.36 to 5.53 | 1.54 -3.75 to 7.48 | 0.65 -4.43 to 6.92 | 0.47 -3.70 to 4.19 | 0.37 -4.78 to 5.55 | PIOGLITAZONE | -0.07 -7.10 to 6.90 | -0.66 -6.36 to 5.09 | -0.76 -7.68 to 6.63 | -1.19 -8.12 to 6.54 | -2.35 -10.71 to 7.66 | -2.46 -9.28 to 5.34 | -4.47 -11.12 to 1.50 |
| METFORMIN | 1.56 -4.04 to 8.82 | 7.40 -1.86 to 17.30 | 5.52 -3.88 to 14.84 | 4.79 -2.06 to 12.44 | 4.75 -2.49 to 13.87 | 3.54 -5.87 to 13.13 | 2.95 -2.89 to 10.19 | 2.81 -2.58 to 9.05 | 2.69 -2.86 to 8.81 | 1.59 -3.96 to 7.61 | 1.56 -4.43 to 8.36 | 0.75 -4.67 to 7.15 | 0.48 -6.40 to 7.32 | 0.43 -4.18 to 5.09 | 0.07 -6.90 to 7.10 | METFORMIN | -0.60 -5.82 to 4.83 | -0.73 -7.60 to 6.88 | -1.08 -7.96 to 6.47 | -2.39 -10.32 to 7.68 | -2.41 -9.38 to 5.42 | -4.40 -11.34 to 2.13 |
| INS_GLARGINE | 2.19 -2.28 to 8.19 | 8.02 -0.40 to 16.92 | 6.09 -2.27 to 14.70 | 5.35 -0.64 to 11.89 | 5.37 -0.94 to 13.40 | 4.12 -4.34 to 12.84 | 3.55 -1.09 to 9.63 | 3.39 -0.47 to 8.02 | 3.25 -0.88 to 8.04 | 2.19 -2.07 to 6.73 | 2.19 -2.62 to 7.70 | 1.37 -2.56 to 6.18 | 1.10 -4.78 to 6.56 | 1.04 -1.58 to 3.61 | 0.66 -5.09 to 6.36 | 0.60 -4.83 to 5.82 | INS_GLARGINE | -0.11 -6.01 to 6.12 | -0.53 -6.24 to 5.79 | -1.67 -9.02 to 7.61 | -1.79 -7.66 to 4.71 | -3.86 -9.55 to 1.49 |
| IDEGLIRA_SC | 2.29 -2.64 to 8.31 | 8.16 -0.84 to 16.87 | 6.25 -2.72 to 14.67 | 5.49 -1.81 to 12.93 | 5.52 -1.37 to 13.29 | 4.21 -4.55 to 12.87 | 3.68 -1.62 to 9.83 | 3.54 -0.95 to 7.97 | 3.45 -2.65 to 9.36 | 2.32 -4.27 to 8.47 | 2.30 -4.16 to 8.82 | 1.49 -3.80 to 7.11 | 1.20 -6.60 to 7.92 | 1.16 -4.76 to 6.42 | 0.76 -6.63 to 7.68 | 0.73 -6.88 to 7.60 | 0.11 -6.12 to 6.01 | IDEGLIRA_SC | -0.39 -7.57 to 7.00 | -1.58 -9.54 to 7.44 | -1.65 -6.02 to 2.61 | -3.70 -11.43 to 3.03 |
| INS_ASPART | 2.61 -2.96 to 9.86 | 8.52 -0.92 to 18.09 | 6.62 -3.08 to 15.95 | 5.89 -0.31 to 11.90 | 5.84 -1.54 to 14.41 | 4.53 -4.87 to 14.22 | 4.02 -1.74 to 10.82 | 3.88 -2.00 to 9.86 | 3.75 -0.29 to 8.02 | 2.70 -3.63 to 8.65 | 2.70 -3.58 to 9.12 | 1.85 -3.38 to 7.60 | 1.63 -5.95 to 8.16 | 1.53 -4.16 to 6.73 | 1.19 -6.54 to 8.12 | 1.08 -6.47 to 7.96 | 0.53 -5.79 to 6.24 | 0.39 -7.00 to 7.57 | INS_ASPART | -1.21 -9.57 to 8.62 | -1.32 -8.40 to 6.32 | -3.35 -11.06 to 3.50 |
| INS_LISPRO | 3.90 -2.76 to 10.37 | 9.70 -1.39 to 19.73 | 7.76 -3.26 to 17.60 | 7.07 -2.74 to 15.65 | 7.04 2.70 to 11.38 | 5.79 -5.36 to 15.94 | 5.28 -2.05 to 12.18 | 5.10 -2.67 to 11.84 | 4.94 -3.66 to 12.43 | 3.90 -5.20 to 11.53 | 3.89 -5.03 to 11.67 | 3.12 -4.96 to 10.08 | 2.78 -7.50 to 10.82 | 2.74 -6.24 to 9.78 | 2.35 -7.66 to 10.71 | 2.39 -7.68 to 10.32 | 1.67 -7.61 to 9.02 | 1.58 -7.44 to 9.54 | 1.21 -8.62 to 9.57 | INS_LISPRO | -0.08 -9.29 to 8.10 | -2.20 -12.22 to 6.14 |
| INS_DEGLUDEC | 3.95 -1.12 to 10.04 | 9.77 0.89 to 18.53 | 7.85 -1.08 to 16.44 | 7.22 -0.40 to 14.81 | 7.16 -0.10 to 15.11 | 5.86 -2.99 to 14.58 | 5.35 -0.15 to 11.50 | 5.20 0.56 to 9.75 | 5.08 -1.11 to 11.03 | 3.97 -2.77 to 10.23 | 3.94 -2.75 to 10.54 | 3.16 -2.39 to 8.75 | 2.87 -4.65 to 9.58 | 2.82 -3.33 to 8.22 | 2.46 -5.34 to 9.28 | 2.41 -5.42 to 9.38 | 1.79 -4.71 to 7.66 | 1.65 -2.61 to 6.02 | 1.32 -6.32 to 8.40 | 0.08 -8.10 to 9.29 | INS_DEGLUDEC | -2.11 -9.82 to 4.80 |
| STANDARD_CARE | 6.12 0.11 to 13.30 | 11.90 2.49 to 21.59 | 9.99 0.60 to 19.62 | 9.27 2.45 to 17.00 | 9.30 1.62 to 18.28 | 7.98 -1.11 to 17.77 | 7.48 1.36 to 14.64 | 7.27 1.89 to 13.51 | 7.18 1.62 to 13.43 | 6.06 1.09 to 11.36 | 6.08 0.34 to 12.62 | 5.28 -0.20 to 11.54 | 4.90 -1.23 to 11.29 | 4.87 0.02 to 9.95 | 4.47 -1.50 to 11.12 | 4.40 -2.13 to 11.34 | 3.86 -1.49 to 9.55 | 3.70 -3.03 to 11.43 | 3.35 -3.50 to 11.06 | 2.20 -6.14 to 12.22 | 2.11 -4.80 to 9.82 | STANDARD_CARE |
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 BMI or body weight (kg/m2) effect modifier, prognostic factor; 24 of 27 |
|---|---|
| NCT00754988 S000027 | 32.47 |
| SURPASS-6 S000108 | 33.15 |
| SCALE™ Insulin S000159 | 35.6 |
| SUSTAIN 11 S000363 | 31.55 |
| SUSTAIN 7 S000372 | 33.5 |
| SURPASS-1 S000407 | 31.9 |
| NCT00717457 S000414 | 33.47 |
| NCT03878706 S000665 | 30 |
| NCT03824002 S000688 | 27.6 |
| NCT01558271 S000837 | 25.51 |
| NCT01147627 S000864 | not reported |
| AWARD-2 S001130 | 31.55 |
| PIONEER 7 S001153 | 31.19 |
| NCT01191268 S001198 | 32.49 |
| AWARD-CHN2 S001404 | 26.77 |
| NCT01126580 S001786 | 33.26 |
| SUSTAIN 8 S001847 | not reported |
| SUSTAIN™ 2 S001876 | 32.5 |
| PIONEER 9 S001943 | 25.9 |
| DUAL™ I Japan S001965 | 26.4 |
| AWARD-1 S002153 | 33.16 |
| NCT01776788 S002224 | 24.96 |
| NCT00700817 S002361 | 32.77 |
| PIONEER 8 S002369 | not reported |
| S002969 S002969 | 36.76 median |
| S003030 S003030 | 24 |
| S003068 S003068 | 27.96 |
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 BMI or body weight: design means range from 24.0 (EXEN_SC vs INS_PREMIX) to 36.2 (LIRA_SC vs PLACEBO) kg/m2; threshold 3
- NoteOutcome assessment, time point: selected time points span 36 to 56 weeks
- NoteOutcome assessment, analysis set: mixed: completers 4, full_analysis 9, modified_itt 7, other 2, randomized 1, safety 4
- NoteOutcome assessment, definition: mixed: HbA1c adjusted for baseline by ANCOVA, participants still in remission 1, HbA1c at 9 months 1, mean HbA1c change baseline to week 52 1, not stated 22, Observed brachial systolic blood pressure at 12 months, mean and SD 1, Observed HbA1c at visit, mean and SD 1
- NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 3, not stated 24
- NoteRisk of bias, blinding: mixed: double_blind 11, open_label 14, single_blind 2
- NoteRisk of bias, funding: mixed: industry 23, mixed 1, non_industry 3
- NoteData handling, input conversions: arms_combined 16, median_converted 2, n_randomized 4
| Trial | time weeks | analysis set | definition | instrument | adjudicated | proportion method | intercurrent events (discontinuation) | intercurrent events (rescue) | blinding | funding | start year | Eligibility |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT00754988 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2008 | age 18 to 75; HbA1c 7.0 to 10.0 percent; BMI 25 (23 Asian) to 45; metformin at least 1500 mg |
| SURPASS-6 | 52 | safety | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2020 | adults 18 or older; HbA1c 7.5 to 11 percent; BMI 23 to 45; basal insulin at least 30 U/day with or without up to 2 oral drugs |
| SCALE™ Insulin | 56 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | age 18 or older; BMI 27 or higher; HbA1c 6.0 to 10 percent; basal insulin plus up to 2 oral drugs |
| SUSTAIN 11 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2018 | adults; HbA1c above 7.5 to 10.0 percent on insulin glargine plus metformin |
| SUSTAIN 7 | 40 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2016 | age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin background |
| SURPASS-1 | 40 | safety | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2019 | adults; HbA1c 7.0 to 9.5 percent; BMI 23 or higher; no glucose lowering drug in prior 90 days |
| NCT00717457 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2008 | age 18 to 75; HbA1c 7 to 10 percent; BMI 25 to 45 (above 23 for Asians); metformin with or without TZD |
| NCT03878706 | 52.14 | completers | Observed brachial systolic blood pressure at 12 months, mean and SD | not stated | not stated | not stated | not stated | not stated | single_blind | non_industry | 2017 | T2D on metformin, HbA1c above 7 percent, high or very high CV risk, eGFR 60 or more |
| NCT03824002 | 39.11 | completers | HbA1c at 9 months | not stated | not stated | not stated | not stated | not stated | single_blind | non_industry | 2017 | age 50 or older; HbA1c 9.5 percent or less; up to two oral drugs with or without basal insulin |
| NCT01558271 | 52 | safety | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2012 | Japanese; age 20 or more; BMI 18.5 to 35; HbA1c 7.0 to 10.0 percent; OAM naive or OAM stopped |
| NCT01147627 | 48 | completers | not stated | not stated | not stated | not stated | not stated | not stated | open_label | mixed | 2010 | newly diagnosed drug naive T2D; age 30 to 70; HbA1c 7 to 10 percent; BMI 20 to 35 |
| 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 |
| PIONEER 7 | 52 | randomized | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2016 | age 18 or more; HbA1c 7.5 to 9.5 percent; one or two oral glucose lowering drugs |
| NCT01191268 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | hypothetical | open_label | industry | 2010 | adults with type 2 diabetes on conventional insulin with or without metformin |
| AWARD-CHN2 | 52 | safety | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2012 | age 18 or older; BMI 19 to 35 kg/m2; HbA1c 7.0 to 11.0 percent on metformin and/or sulfonylurea |
| NCT01126580 | 52 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2010 | type 2 diabetes on diet and exercise or one oral drug; registry gives no ranges |
| 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 |
| SUSTAIN™ 2 | 56 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2013 | type 2 diabetes on metformin and or thiazolidinedione; HbA1c 7.0 to 10.5 percent |
| PIONEER 9 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | Japanese adults 20 y or older; HbA1c 6.5 to 9.5 on one oral drug washed out, or 7.0 to 10.0 on diet and exercise |
| DUAL™ I Japan | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2015 | Japanese adults 20 or older; HbA1c 7.0 to 11.0 percent; BMI at least 20; insulin naive on one oral drug |
| 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 |
| NCT01776788 | 52.18 | other | HbA1c adjusted for baseline by ANCOVA, participants still in remission | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2012 | age 30 to 70; newly diagnosed drug naive; FPG 7.0 to 16.7 mmol/L; BMI 20 to 35 |
| NCT00700817 | 52 | other | not stated | not stated | not stated | not stated | not stated | not stated | open_label | industry | 2008 | age 18 to 80; HbA1c 7.5 to 10%; BMI 45 or less; metformin 1500 mg/day or more for 3 months |
| PIONEER 8 | 52 | full_analysis | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 2017 | adults with type 2 diabetes on basal, premixed or basal bolus insulin with or without metformin |
| S002969 | 52.14 | modified_itt | not stated | not stated | not stated | not stated | not stated | not stated | double_blind | industry | 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 | not stated | open_label | industry | 2015 | age 20 to 75; HbA1c 7.5 to 11 percent; two or more oral agents for 3 months |
| S003068 | 36 | completers | Observed HbA1c at visit, mean and SD | not stated | not stated | not stated | not stated | not stated | open_label | non_industry | insulin treated T2D, age over 20, BMI 25 or more, HbA1c 7 to 10% |
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 | -2.749 | 0.675 | 369 | arms_combined | R0022521:Table 5 |
| NCT00754988 | A4 | SITAGLIPTIN | 52 | arm, change | -1.700 | 0.972 | 177 | R0022521:Table 5 | |
| SURPASS-6 | A1+A2+A3 | TIRZ_SC | 52 | arm, change | -7.437 | 0.463 | 717 | n_randomized;arms_combined | R0009666:Supplement eTable 7 |
| SURPASS-6 | A4 | INS_LISPRO | 52 | arm, change | -0.400 | 0.459 | 711 | n_randomized | R0009666:Supplement eTable 7 |
| SCALE™ Insulin | A1 | LIRA_SC | 56 | arm, change | -6.000 | 0.995 | 198 | registry:outcomes | |
| SCALE™ Insulin | A2 | PLACEBO | 56 | arm, change | -2.000 | 1.066 | 198 | registry:outcomes | |
| SUSTAIN 11 | A1 | SEMA_SC | 52 | arm, change | -2.800 | 0.493 | 784 | registry:outcomes | |
| SUSTAIN 11 | A2 | INS_ASPART | 52 | arm, change | 1.000 | 0.506 | 765 | registry:outcomes | |
| SUSTAIN 7 | A1+A2 | SEMA_SC | 40 | arm, change | -3.658 | 0.543 | 601 | arms_combined | registry:outcomes |
| SUSTAIN 7 | A3+A4 | DULA_SC | 40 | arm, change | -2.510 | 0.530 | 598 | arms_combined | registry:outcomes |
| SURPASS-1 | A2 | TIRZ_SC | 40 | contrast, md | -3.100 | 1.607 | R0009496:Results | ||
| SURPASS-1 | A4 | PLACEBO | 40 | contrast, md | R0009496:Results | ||||
| NCT00717457 | A1+A2 | TASP_SC | 52 | arm, change | -2.099 | 0.881 | 776 | arms_combined | R0013639:Supplementary Table |
| NCT00717457 | A3 | EXEN_SC | 52 | arm, change | -2.390 | 1.245 | 373 | R0013639:Supplementary Table | |
| NCT03878706 | A1 | OTHER_ACTIVE_basal_insulin | 52.14 | arm, final | 134.000 | 2.372 | 40 | R0008057:Table 3 | |
| NCT03878706 | A2 | LIRA_SC | 52.14 | arm, final | 135.000 | 2.372 | 40 | R0008057:Table 3 | |
| NCT03878706 | A3 | EMPAGLIFLOZIN | 52.14 | arm, final | 130.000 | 2.372 | 40 | R0008057:Table 3 | |
| NCT03878706 | A4 | EMPALIRA_SC | 52.14 | arm, final | 132.000 | 2.214 | 40 | R0008057:Table 3 | |
| NCT03824002 | A1 | DULA_SC | 39.11 | arm, final | 129.700 | 1.430 | 56 | R0017066:Table 2 | |
| NCT03824002 | A2 | STANDARD_CARE | 39.11 | arm, final | 132.700 | 2.232 | 56 | R0017066:Table 2 | |
| NCT01558271 | A1 | DULA_SC | 52 | arm, change | 1.450 | 0.640 | 281 | n_randomized | R0011754:Table 2 |
| NCT01558271 | A2 | LIRA_SC | 52 | arm, change | -1.580 | 0.920 | 141 | n_randomized | R0011754:Table 2 |
| NCT01147627 | A1 | EXEN_SC | 48 | arm, change | -2.400 | 0.245 | 88 | R0021706:Table 1 | |
| NCT01147627 | A2 | INS_PREMIX | 48 | arm, change | -1.600 | 0.251 | 84 | R0021706:Table 1 | |
| NCT01147627 | A3 | PIOGLITAZONE | 48 | arm, change | -1.000 | 0.096 | 109 | R0021706:Table 1 | |
| AWARD-2 | A1+A2 | DULA_SC | 52 | arm, change | 0.130 | 0.569 | 502 | arms_combined | registry:outcomes |
| AWARD-2 | A3 | INS_GLARGINE | 52 | arm, change | 0.510 | 0.830 | 240 | registry:outcomes | |
| PIONEER 7 | A1+A3 | SEMA_PO | 52 | arm, change | -3.000 | 0.834 | 293 | arms_combined | registry:outcomes |
| PIONEER 7 | A2+A4 | SITAGLIPTIN | 52 | arm, change | -0.830 | 0.846 | 318 | arms_combined | registry:outcomes |
| NCT01191268 | A1+A2 | DULA_SC | 52 | arm, change | 0.391 | 0.661 | 479 | arms_combined | registry:outcomes |
| NCT01191268 | A3 | INS_GLARGINE | 52 | arm, change | 1.980 | 0.920 | 246 | registry:outcomes | |
| AWARD-CHN2 | A1+A2 | DULA_SC | 52 | arm, change | -1.397 | 0.513 | 515 | arms_combined | R0023722:Table 2 |
| AWARD-CHN2 | A3 | INS_GLARGINE | 52 | arm, change | -0.250 | 0.737 | 253 | R0023722:Table 2 | |
| NCT01126580 | A1+A2 | DULA_SC | 52 | arm, change | -1.419 | 0.625 | 440 | arms_combined | registry:outcomes |
| NCT01126580 | A3 | METFORMIN | 52 | arm, change | -0.980 | 0.880 | 215 | registry:outcomes | |
| SUSTAIN 8 | A1 | SEMA_SC | 52 | arm, change | -3.700 | 0.705 | 394 | registry:outcomes | |
| SUSTAIN 8 | A2 | CANAGLIFLOZIN | 52 | arm, change | -5.800 | 0.680 | 394 | registry:outcomes | |
| SUSTAIN™ 2 | A1+A2 | SEMA_SC | 56 | arm, change | -5.340 | 0.449 | 818 | arms_combined | registry:outcomes |
| SUSTAIN™ 2 | A3 | SITAGLIPTIN | 56 | arm, change | -2.290 | 0.670 | 407 | registry:outcomes | |
| PIONEER 9 | A1+A2+A3 | SEMA_PO | 52 | arm, change | -0.664 | 0.881 | 146 | arms_combined | registry:outcomes |
| PIONEER 9 | A4 | LIRA_SC | 52 | arm, change | 1.000 | 2.165 | 48 | registry:outcomes | |
| PIONEER 9 | A5 | PLACEBO | 52 | arm, change | -3.000 | 1.286 | 49 | registry:outcomes | |
| DUAL™ I Japan | A1 | IDEGLIRA_SC | 52 | arm, change | 1.700 | 0.724 | 275 | registry:outcomes | |
| DUAL™ I Japan | A2 | INS_DEGLUDEC | 52 | arm, change | 3.400 | 0.869 | 271 | registry:outcomes | |
| DUAL™ I Japan | A3 | LIRA_SC | 52 | arm, change | -1.800 | 0.787 | 273 | registry:outcomes | |
| AWARD-1 | A1+A2 | DULA_SC | 52 | arm, change | 1.231 | 0.608 | 504 | arms_combined | registry:outcomes |
| AWARD-1 | A3 | EXEN_SC | 52 | arm, change | 0.020 | 0.880 | 238 | registry:outcomes | |
| NCT01776788 | A1 | STANDARD_CARE | 52.18 | arm, final | 130.200 | 2.959 | R0024844:Table 1 | ||
| NCT01776788 | A2 | EXEN_SC | 52.18 | arm, final | 124.700 | 1.990 | R0024844:Table 1 | ||
| NCT00700817 | A1+A2 | LIRA_SC | 52 | arm, change | -1.463 | 0.659 | 427 | arms_combined | R0024199:Table 1 |
| NCT00700817 | A3 | SITAGLIPTIN | 52 | arm, change | -1.030 | 0.929 | 213 | R0024199:Table 1 | |
| PIONEER 8 | A1+A2+A3 | SEMA_PO | 52 | arm, change | -3.321 | 0.608 | 546 | arms_combined | registry:outcomes |
| PIONEER 8 | A4 | PLACEBO | 52 | arm, change | 0.000 | 1.032 | 184 | registry:outcomes | |
| S002969 | A1 | LIRA_SC | 52.14 | arm, change | 0.777 | 3.137 | 12 | median_converted | R0010852:Supplementary Table 12 |
| S002969 | A2 | PLACEBO | 52.14 | arm, change | -0.333 | 3.766 | 13 | median_converted | R0010852:Supplementary Table 12 |
| S003030 | A1 | EXEN_SC | 52 | arm, change | -1.850 | 2.762 | 27 | R0018574:Table 2 | |
| S003030 | A2 | INS_PREMIX | 52 | arm, change | 2.250 | 3.313 | 32 | R0018574:Table 2 | |
| S003068 | A1 | LIRA_SC | 36 | arm, final | 126.000 | 4.950 | 8 | R0025603:Table 3 | |
| S003068 | A2 | STANDARD_CARE | 36 | arm, final | 143.000 | 4.667 | 9 | R0025603:Table 3 |
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