(A) Sensitivity analyses | |||||
---|---|---|---|---|---|
Outcome | Comparator | ||||
Gla-100 | Detemir | NPH | Degludec | Premix | |
Change in HbA1c* | |||||
BOT, insulin naïve | 0.01 (−0.27 to 0.29) | −0.14 (−0.47 to 0.19) | −0.09 (−0.43 to 0.25) | −0.12 (−0.45 to 0.21) | 0.08 (−0.23 to 0.39) |
Adjusting for Bolus Insulin Trials | −0.01 (−0.44 to 0.42) | −0.10 (−0.55 to 0.36) | −0.05 (−0.51 to 0.41) | −0.14 (−0.60 to 0.33) | 0.07 (−0.37 to 0.51) |
Insulin naïve | 0.04 (−0.41 to 0.48) | −0.09 (−0.59 to 0.40) | −0.06 (−0.55 to 0.43) | −0.12 (−0.62 to 0.37) | 0.24 (−0.22 to 0.72) |
T2DM overall | 0.01 (−0.23 to 0.25) | −0.08 (−0.37 to 0.21) | −0.03 (−0.32 to 0.26) | −0.12 (−0.42 to 0.18) | 0.09 (−0.18 to 0.35) |
Studies reporting hypoglycaemia data | 0.01 (−0.23 to 0.25) | −0.18 (−0.51 to 0.14) | −0.09 (−0.57 to 0.38) | −0.12 (−0.42 to 0.18) | 0.18 (−0.12 to 0.51) |
Studies with 24–28-week results | 0.01 (−0.24 to 0.26) | −0.04 (−0.36 to 0.27) | −0.03 (−0.35 to 0.30) | −0.14 (−0.47 to 0.19) | 0.17 (−0.10 to 0.45) |
Excluding Degludec 3TW | 0.02 (−0.22 to 0.28) | −0.08 (−0.37 to 0.22) | 0.01 (−0.26 to 0.30) | −0.01 (−0.32 to 0.31) | 0.26 (−0.02 to 0.55) |
Adjusting for baseline HbA1c | 0.05 (−0.49 to 0.63) | −0.03 (−0.60 to 0.56) | 0.02 (−0.56 to 0.61) | −0.07 (−0.65 to 0.53) | 0.13 (−0.42 to 0.72) |
Adjusting for disease duration | 0.03 (−0.29 to 0.34) | −0.06 (−0.41 to 0.29) | −0.01 (−0.37 to 0.35) | −0.10 (−0.46 to 0.26) | 0.11 (−0.23 to 0.44) |
Change in body weight | |||||
BOT, insulin naïve | −0.44 (−1.67 to 0.81) | 0.58 (−0.85 to 2.03) | −0.22 (−1.68 to 1.25) | −0.52 (−1.93 to 0.92) | −1.09 (−2.44 to 0.29) |
Adjusting for Bolus Insulin Trials | −0.58 (−2.54 to 1.37) | 0.11 (−1.98 to 2.20) | −0.63 (−2.75 to 1.45) | −0.66 (−2.78 to 1.45) | −1.13 (−3.18 to 0.91) |
Insulin naïve | −0.30 (−1.44 to 0.82) | 1.18 (−0.12 to 2.47) | −0.12 (−1.39 to 1.10) | −0.46 (−1.71 to 0.80) | −1.12 (−2.39 to 0.15) |
T2DM overall | −0.27 (−1.28 to 0.73) | 0.42 (−0.78 to 1.62) | −0.32 (−1.54 to 0.89) | −0.35 (−1.58 to 0.88) | −0.81 (−1.96 to 0.32) |
Studies reporting hypoglycaemia data | −0.28 (−1.28 to 0.71) | 1.01 (−0.29 to 2.31) | 0.89 (−0.90 to 2.70) | −0.36 (−1.58 to 0.86) | −1.24 (−2.59 to 0.09) |
Studies with 24–28-week results | −0.28 (−1.28 to 0.74) | 0.26 (−1.05 to 1.57) | −0.15 (−1.45 to 1.16) | −0.42 (−1.76 to 0.92) | −1.01 (−2.19 to 0.18) |
Excluding Degludec 3TW | −0.46 (−1.34 to 0.43) | 0.68 (−0.38 to 1.76) | −0.76 (−1.82 to 0.27) | −0.79 (−1.90 to 0.33) | −1.83 (−2.89 to −0.68) |
Adjusting for baseline HbA1c | −0.27 (−2.03 to 1.25) | 0.43 (−1.46 to 2.12) | −0.32 (−2.23 to 1.39) | −0.34 (−2.26 to 1.38) | −0.81 (−2.68 to 0.82) |
Adjusting for disease duration | −0.44 (−1.91 to 1.00) | 0.25 (−1.38 to 1.87) | −0.49 (−2.15 to 1.13) | −0.52 (−2.20 to 1.13) | −0.99 (−2.58 to 0.58) |
Nocturnal hypoglycaemia event rate | |||||
BOT, insulin naïve | 0.57 (0.33 to 0.98) | 0.53 (0.28 to 1.01) | 0.21 (0.10 to 0.44) | 0.68 (0.36 to 1.25) | 0.42 (0.21 to 0.81) |
BOT, premixed excluded | 0.62 (0.37 to 1.17) | 0.56 (0.30 to 1.21) | 0.16 (0.08 to 0.41) | 0.79 (0.42 to 1.64) | N/A |
Adjusting for Bolus Insulin Trials | 0.56 (0.24 to 1.29) | 0.52 (0.21 to 1.32) | 0.20 (0.07 to 0.57) | 0.66 (0.26 to 1.61) | 0.50 (0.19 to 1.26) |
Insulin naïve patients only | 0.58 (0.12 to 2.77) | 0.51 (0.07 to 3.38) | 0.17 (0.02 to 1.37) | 0.61 (0.10 to 3.48) | 0.26 (0.03 to 2.35) |
T2DM overall | 0.64 (0.39 to 1.03) | 0.60 (0.32 to 1.11) | 0.23 (0.11 to 0.50) | 0.75 (0.41 to 1.34) | 0.57 (0.31 to 1.05) |
Studies with 24–28-week results | 0.64 (0.37 to 1.10) | 0.51 (0.22 to 1.18) | 0.24 (0.08 to 0.70) | 0.67 (0.32 to 1.37) | 0.55 (0.26 to 1.17) |
Excluding Degludec 3TW | 0.57 (0.33 to 0.98) | 0.51 (0.24 to 1.07) | 0.19 (0.07 to 0.45) | 0.83 (0.42 to 1.69) | 0.36 (0.17 to 0.74) |
2.8–4.2 mmol/L | 0.64 (0.37 to 1.11) | 0.68 (0.35 to 1.34) | 0.31 (0.15 to 0.63) | 0.75 (0.38 to 1.46) | 0.68 (0.35 to 1.29) |
Adjusting for baseline HbA1c | 0.37 (0.18 to 0.90) | 0.35 (0.15 to 0.91) | 0.13 (0.05 to 0.39) | 0.43 (0.19 to 1.12) | 0.33 (0.14 to 0.86) |
Adjusting for disease duration | 0.60 (0.31 to 1.13) | 0.56 (0.26 to 1.19) | 0.22 (0.09 to 0.53) | 0.71 (0.34 to 1.46) | 0.54 (0.25 to 1.14) |
Documented symptomatic hypoglycaemia event rate | |||||
BOT, insulin naïve | 0.72 (0.40 to 1.30) | 0.63 (0.22 to 1.73) | 0.58 (0.26 to 1.24) | 0.59 (0.29 to 1.20) | 0.50 (0.24 to 1.01) |
BOT, premixed excluded | 0.75 (0.55 to 1.05) | 0.69 (0.42 to 1.23) | 0.55 (0.36 to 0.91) | 0.66 (0.46 to 1.01) | N/A |
Adjusting for Bolus Insulin Trials | 0.83 (0.35 to 1.83) | 0.72 (0.22 to 2.31) | 0.76 (0.28 to 1.86) | 0.68 (0.26 to 1.67) | 0.57 (0.22 to 1.41) |
Insulin naïve patients only | 0.62 (0.21 to 1.77) | 0.54 (0.12 to 2.36) | 0.50 (0.14 to 1.63) | 0.61 (0.17 to 2.25) | 0.24 (0.05 to 1.09) |
T2DM overall | 0.78 (0.50 to 1.23) | 0.68 (0.27 to 1.70) | 0.71 (0.38 to 1.30) | 0.64 (0.36 to 1.16) | 0.54 (0.30 to 0.98) |
Studies with 24–28-week results | 0.78 (0.45 to 1.34) | 0.68 (0.23 to 2.01) | 0.75 (0.36 to 1.60) | 0.53 (0.23 to 1.20) | 0.58 (0.27 to 1.25) |
Adjusting for baseline HbA1c | 0.71 (0.44 to 1.13) | 0.61 (0.25 to 1.51) | 0.64 (0.34 to 1.19) | 0.58 (0.32 to 1.05) | 0.49 (0.27 to 0.89) |
Adjusting for disease duration | 0.57 (0.32 to 0.99) | 0.50 (0.18 to 1.33) | 0.52 (0.25 to 1.04) | 0.47 (0.23 to 0.92) | 0.40 (0.19 to 0.78) |
(B) Comparison of NMA to classic meta-analysis for base scenario (BOT) | |||
---|---|---|---|
Outcome | Difference | NMA: point estimate (95% CrI) | Meta-analysis (direct evidence): point estimate (95% CI) |
Change in HbA1c† | Gla-300 vs Gla-100 | 0.01 (−0.27 to 0.29) | 0.02 (−0.08 to 0.11) |
Insulin detemir vs Gla-100 | 0.10 (−0.07 to 0.28) | 0.04 (−0.05 to 0.13) | |
NPH vs Gla-100 | 0.01 (−0.14 to 0.16) | 0.02 (−0.05 to 0.09) | |
Insulin degludec vs Gla-100 | 0.14 (−0.03 to 0.30) | 0.13 (0.06 to 0.20) | |
Premixed vs Gla-100 | −0.24 (−0.40 to −0.08) | −0.15 (−0.21 to −0.10) | |
Change in body weight | Gla-300 vs Gla-100 | −0.44 (−1.67 to 0.81) | −0.48 (−0.83 to −0.13) |
Insulin detemir vs Gla-100 | −1.15 (−1.73 to −0.58) | −0.98 (−1.20 to −0.76) | |
NPH vs Gla-100 | 0.30 (−0.21 to 0.84) | 0.01 (−0.22 to 0.25) | |
Insulin degludec vs Gla-100 | 0.18 (−0.35 to 0.70) | 0.21 (0.03 to 0.38) | |
Premixed vs Gla-100 | 1.37 (0.72 to 1.97) | 1.70 (1.69 to 1.71) | |
Nocturnal hypoglycaemia event rate | Gla-300 vs Gla-100 | 0.57 (0.33 to 0.98) | 0.59 (0.38 to 0.90) |
Insulin detemir vs Gla-100 | 1.11 (0.58 to 2.10) | 1.06 (0.93 to 1.21) | |
NPH vs Gla-100 | 3.04 (1.24 to 7.80) | NA† | |
Insulin degludec vs Gla-100 | 0.88 (0.57 to 1.38) | 0.79 (0.67 to 0.93) | |
Premixed vs Gla-100 | 1.60 (0.84 to 3.10) | 1.39 (1.19 to 1.62) | |
Documented symptomatic hypoglycaemia event rate | Gla-300 vs Gla-100 | 0.72 (0.40 to 1.30) | 0.75 (0.61 to 0.92) |
Insulin detemir vs Gla-100 | 1.15 (0.44 to 2.96) | 1.15 (1.07 to 1.24) | |
NPH vs Gla-100 | 1.10 (0.68 to 1.89) | 1.04 (1.00 to 1.09) | |
Insulin degludec vs Gla-100 | 1.30 (0.75 to 2.24) | 1.35 (1.27 to 1.44) | |
Premixed vs Gla-100 | NA† | NA† |
*Four additional studies were included in sensitivity analyses for HbA1c and/or body weight, but were not in the main NMA.47–50
†No direct evidence for specific comparison.
BOT, basal insulin-supported oral therapy (ie, no bolus insulin); CrI, Credible interval; HbA1c, glycated haemoglobin; NA, not applicable; NMA, network meta-analysis; NPH, neutral protamine Hagedorn; T2DM, type 2 diabetes mellitus.