Changes in outcome from trial entry to 18 months*
| Biphasic (n=137) | Aspart+detemir (n=138) | Detemir (n=137) | p Value biphasic vs aspart+detemir | p Value biphasic vs detemir | p Value aspart+detemir vs detemir | |
|---|---|---|---|---|---|---|
| Carotid ultrasound measures | ||||||
| Mean carotid IMT (mm)† | −0.009 (−0.022 to 0.004) | 0.000 (−0.013 to 0.013) | −0.012 (−0.025 to 0.000) | 0.2720 | 0.8173 | 0.1871 |
| Maximal carotid IMT (mm) | −0.010 (−0.025 to 0.005) | 0.001 (−0.014 to 0.016) | −0.016 (−0.031 to −0.001) | 0.2935 | 0.5734 | 0.1095 |
| Body composition | ||||||
| Weight (kg) | 3.3 (2.7 to 4.0) | 3.2 (2.6 to 3.9) | 1.9 (1.3 to 2.6) | 0.8102 | 0.0026 | 0.0055 |
| Body mass index (kg/m2) | 1.1 (0.9 to 1.3) | 1.0 (0.8 to 1.2) | 0.6 (0.4 to 0.8) | 0.7037 | 0.0021 | 0.0071 |
| Waist−hip ratio | 0.00 (−0.01 to 0.01) | 0.01 (0.00 to 0.02) | 0.01 (0.00 to 0.02) | 0.0926 | 0.0484 | 0.7516 |
| Glycaemic control | ||||||
| HbA1c (%) | −1.00 (−1.16 to −0.83) | −0.45 (−0.61 to −0.28) | −0.26 (−0.43 to −0.09) | <0.001 | <0.001 | 0.1304 |
| HbA1c (mmol/mol) | −10.9 (−12.7 to −9.1) | −4.9 (−6.7 to −3.1) | −2.8 (−4.7 to −1.0) | <0.001 | <0.001 | 0.1304 |
| HbA1c at 18 months (%) | 7.78 (7.56 to 8.00) | 8.19 (7.98 to 8.42) | 8.42 (8.20 to 8.64) | 0.0019 | <0.001 | 0.1074 |
| HbA1c at 18 months (mmol/mol) | 62 (59 to 64) | 66 (64 to 69) | 69 (66 to 71) | 0.0019 | <0.001 | 0.1074 |
| N (%) participants with HbA1c≤7.0% at end-of-trial | 38 (28) | 31 (22) | 12 (9) | 0.306 | 0.000 | 0.005 |
| Fasting p-glucose, mmol/L | −2.0 (−2.6 to −1.4) | −1.3 (−1.9 to −0.7) | −2.4 (−3.1 to −1.8) | 0.1108 | 0.3347 | 0.0109 |
| Fasting p-insulin (relative change from baseline) | 0.92 (0.78 to 1.09) | 0.57 (0.48 to 0.67) | 0.52 (0.44 to 0.62) | <0.001 | <0.001 | 0.5103 |
| Fasting C peptide (relative change from baseline) | 0.85 (0.76 to 0.94) | 0.70 (0.63 to 0.78) | 0.60 (0.54 to 0.67) | 0.0110 | <0.001 | 0.0480 |
| Insulin dose, end-of-trial (IU/kg/day) | 0.96 (0.86 to 1.08) | 1.15 (1.02 to 1.29) | 1.58 (1.40 to 1.78) | 0.0064 | <0.001 | <0.001 |
| Insulin dose, end-of-trial (IU/day) | 95 (84 to 108) | 116 (102 to 132) | 158 (139 to 180) | 0.080 | <0.001 | <0.001 |
| Insulin dose (relative change from baseline) | 1.96 (1.82 to 2.11) | 2.27 (2.10 to 2.45) | 3.37 (3.11 to 3.65) | 0.006 | <0.001 | <0.001 |
| Blood pressure and lipids | ||||||
| Systolic blood pressure (mm Hg) | −6.7 (−9.4 to −3.9) | −6.0 (−8.8 to −3.1) | −3.5 (−6.4 to −0.6) | 0.7282 | 0.1249 | 0.2391 |
| Diastolic blood pressure (mm Hg) | −3.3 (−4.8 to −1.8) | −2.9 (−4.4 to −1.4) | −3.5 (−5.1 to −1.9) | 0.6996 | 0.8795 | 0.5998 |
| Heart rate (bpm) | −1.3 (−3.1 to 0.4) | −0.5 (−2.3 to 1.2) | −3.0 (−4.8 to −1.2) | 0.5168 | 0.1853 | 0.0532 |
| Total cholesterol (mmol/L) | 0.17 (0.03 to 0.31) | 0.05 (−0.09 to 0.19) | 0.19 (0.05 to 0.33) | 0.2323 | 0.8254 | 0.1603 |
| LDL cholesterol (mmol/L) | 0.15 (0.04 to 0.27) | 0.06 (−0.06 to 0.18) | 0.17 (0.05 to 0.29) | 0.2634 | 0.9012 | 0.2187 |
| VLDL cholesterol (relative change from baseline) | 0.96 (0.90 to 1.03) | 1.02 (0.95 to 1.09) | 1.01 (0.94 to 1.09) | 0.2821 | 0.3111 | 0.9578 |
| HDL cholesterol (mmol/L) | 0.03 (−0.00 to 0.07) | −0.01 (−0.05 to 0.03) | −0.01 (−0.05 to 0.02) | 0.1112 | 0.0840 | 0.8722 |
| Triglycerides (relative change from baseline) | 0.97 (0.91 to 1.05) | 1.00 (0.93 to 1.08) | 1.02 (0.95 to 1.10) | 0.5826 | 0.3541 | 0.6989 |
The variables p-insulin, C peptide, insulin dose, VLDL cholesterol and triglycerides did not meet the criteria of a normal distribution and were accordingly log transformed. Therefore, these variables are presented in table 2 with relative change from baseline instead of absolute change.
To adjust for multiplicity, the significance level can be adjusted to 0.05/(K+1)/2 (where K represents the number of prespecified secondary outcomes) equalling, in this case, an α=0.0045.
*Intention-to-treat, mixed model analyses with random-effect person adjusted for stratification variables, results are presented as mean (95% CI).
†Between-group differences are analysed using multiple imputation of missing values.
HbA1c, glycated haemoglobin; HDL, high-density lipoprotein; IMT, intima-media thickness; LDL, low-density lipoprotein; VLDL, very low-density lipoprotein.