Table 3.
Results from the main analysis: 4-arm model with 56 patients in the basal–bolus arm
| (a) Estimated end-of-trial HbA1c values, changes from baseline to end-of-treatment per treatment arm, and daily basal insulin dose at end of treatment, based on ANCOVA model | ||||||||
|---|---|---|---|---|---|---|---|---|
| IDegLira (N = 199) | GLP-1RA add-on to basal insulin (N = 225) | Basal–bolus with insulin glargine as basal component (N = 56) | Basal-only (up-titrated insulin glargine) (N = 329) | |||||
| Mean (SD) | 95% CI | Mean (SD) | 95% CI | Mean (SD) | 95% CI | Mean (SD) | 95% CI | |
| EOT HbA1c (%) | 6.74 (0.94) | (6.60; 6.88) | 7.09 [0.94) | (6.94; 7.24) | 7.04 (0.94) | (6.78; 7.29) | 7.39 (0.94) | (7.28; 7.49) |
| ΔHbA1c (%) | −1.68 (0.94) | (−1.82; −1.54) | −1.33** (0.94) | (−1.48; −1.18) | −1.39* (0.94) | (−1.64; −1.13) | −1.03** (0.94) | (−1.14; −0.93) |
| ΔHbA1c (mmol/mol)a | −18 (11) | (−20; −17) | −15** (13) | (−16; −13) | −15* (11) | (−18; −12) | −11** (11) | (−12; −10) |
| Δbody weight (kg) | −2.88 (3.42) | (−3.39; −2.37) | −3.53 (3.42) | (−4.08; −2.97) | 4.01** (3.42) | (3.10; 4.93) | 1.16** (3.42) | (0.78; 1.55) |
| ΔBMI (kg/m2) | −1.02 (1.21) | (–1.19; −0.84) | −1.27 (1.21) | (−1.47; −1.08) | 1.42** (1.21) | (1.10; 1.75) | 0.43** (1.21) | (0.29; 0.56) |
| ΔSBP (mmHg) | −6.84 (12.95) | (−8.76; −4.92) | −4.68 (12.95) | (−6.75; −2.61) | 1.83** (12.95) | (−1.64; 5.30) | −3.47** (12.95) | (−4.92; −2.01) |
| Δtotal cholesterol (mg/dL) | −10.44 (29.67) | (−14.84; −6.05) | −13.26 (29.67) | (−18.02; −8.50) | −5.80 (29.67) | (−13.76; 2.15) | −2.88** (29.67) | (−6.24; 0.48) |
| ΔLDL cholesterol (mg/dL) | −7.56 (24.07) | (−11.12; −3.99) | −9.86 (24.07) | (−13.73; −5.98) | −3.13 (24.07) | (−9.58; 3.32) | −2.73* (24.07) | (−5.45; −0.01) |
| ΔHDL cholesterol (mg/dL) | 0.47 (6.74) | (−0.53; 1.47) | −0.74 (6.74) | (−1.82; 0.34) | 0.40 (6.74) | (−1.41; 2.20) | 1.06 (6.74) | (0.30; 1.82) |
| Δtriglycerides (mg/dL) | −18.61 (78.66) | (−30.29; −6.92) | −16.56 (78.66) | (−29.17; −3.94) | −16.14 (78.66) | (−37.22; 4.93) | −9.43 (78.66) | (−18.39; −0.47) |
| EOT daily basal dose (U) | 37.80 (27.05)b | (33.79; 41.80) | 36.63 (27.05)c | (32.33; 40.93) | 62.43** (27.05)d | (55.19; 69.68) | 60.65* (27.05) | (57.59; 63.72) |
| (b) Estimated end-of-treatment differences for IDegLira versus comparators, and daily insulin dose at end of treatment, based on ANCOVA model | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| IDegLira versus GLP-1RA add-on to basal insulin | IDegLira versus basal–bolus with insulin glargine as basal component | IDegLira versus basal-only (up-titrated insulin glargine) | |||||||
| Mean | 95% CI | P value | Mean | 95% CI | P value | Mean | 95% CI | P value | |
| ΔHbA1c(%) | −0.35 | (−0.56; −0.14) | 0.0009 | −0.30 | (−0.58; −0.01) | 0.040 | −0.65 | (−0.83; −0.47) | <0.0001 |
| ΔHbA1c (mmol/mol)a | −4 | (−6; −2) | 0.0009 | −3 | (−6; 0) | 0.040 | −7 | (−9; −5) | <0.0001 |
| Δbody weight (kg) | 0.65 | (−0.11; 1.40) | 0.092 | −6.89 | (−7.92; −5.86) | <0.0001 | −4.04 | (−4.69; −3.40) | <0.0001 |
| ΔBMI (kg/m2) | 0.26 | (−0.01; 0.52) | 0.058 | −2.44 | (−2.80; −2.07) | <0.0001 | −1.44 | (−1.67; −1.21) | <0.0001 |
| ΔSBP (mmHg) | −2.16 | (−5.01; 0.69) | 0.14 | −8.67 | (−12.58; −4.77) | <0.0001 | −3.37 | (−5.80; −0.94) | 0.0065 |
| Δtotal cholesterol (mg/dL) | 2.82 | (−3.71; 9.34) | 0.40 | −4.64 | (−13.60; 4.31) | 0.31 | −7.56 | (−13.16; −1.97) | 0.0081 |
| ΔLDL cholesterol (mg/dL) | 2.30 | (−3.00; 7.60) | 0.39 | −4.43 | (−11.68; 2.83) | 0.23 | −4.82 | (−9.35; −0.30) | 0.037 |
| ΔHDL cholesterol (mg/dL) | 1.21 | (−0.27; 2.70) | 0.11 | 0.07 | (−1.96; 2.10) | 0.94 | −0.59 | (−1.86; 0.67) | 0.36 |
| Δtriglycerides (mg/dL) | −2.05 | (−19.36; 15.26) | 0.82 | −2.46 | (−26.20; 21.27) | 0.84 | −9.18 | (−24.10; 5.74) | 0.23 |
| Daily basal dose EOT (U) | 1.17 | (−4.75; 7.09) | 0.70 | −24.64 | (−32.79; −16.49) | <0.0001 | −22.86 | (−27.94; −17.78) | <0.0001 |
IDegLira significantly different: * P < 0.05, ** P < 0.01 (for exact values see Table 3b). Reported SDs are model based
Δ change from baseline, ANCOVA analysis of covariance, BMI body mass index, CI confidence interval, EOT end of treatment, GLP-1RA glucagon-like peptide-1 receptor agonist, HbA 1c glycated hemoglobin, HDL high-density lipoprotein, IDegLira insulin degludec/liraglutide, LDL low-density lipoprotein, SBP systolic blood pressure, SD standard deviation
aCalculated values
bDaily GLP-1RA dose at end of treatment was 1.36 mg (one dose step of IDegLira = 1 U insulin degludec + 0.036 mg liraglutide)
cDaily GLP-1RA dose at end of treatment was 1.8 mg
dDaily bolus dose at end of treatment was 53.60 U. Basal/bolus dose split: 53.8%/46.2%