Introduction
Materials and Methods
Assessments and Outcome Measures
Statistical Analysis
Results
Study Participants
Baseline variable | Age ≤40 years | Age >40–65 years | Age >65 years |
---|---|---|---|
Entire cohort, n
| 1,467 | 10,967 | 2,807 |
Insulin status, n
| |||
Insulin-experienced | 258 | 2,286 | 840 |
Insulin-naïve | 1,209 | 8,681 | 1,967 |
Gender (male/female) (%)a
| 63.4/36.6 | 55.4/44.6 | 43.4/56.6 |
Mean (SD) age (years) | 34.9 (5.8) | 53.0 (6.5) | 71.6 (5.0) |
Mean (SD) body weight (kg)b
| 77.4 (16.1) | 77.3 (16.7) | 69.5 (14.6) |
Mean (SD) BMI (kg/m2)c
| 28.0 (5.2) | 28.5 (5.4) | 26.9 (5.0) |
Mean (SD) age at diagnosis (years)d
| 30.9 (5.6) | 45.0 (7.1) | 59.3 (9.0) |
Mean (SD) diabetes duration (y)d
| 4.3 (3.3) | 8.0 (5.2) | 12.3 (7.8) |
Safety Measures
Insulin Dose
Mean (SD) insulin dose (U/kg) | Age ≤40 years | Age >40–65 years | Age >65 years | |||
---|---|---|---|---|---|---|
Baseline | 24 weeks | Baseline | 24 weeks | Baseline | 24 weeks | |
Entire cohort | 0.29 (0.16) | 0.37 (0.20) | 0.26 (0.15) | 0.37 (0.20) | 0.27 (0.16) | 0.38 (0.21) |
n
| 1,401 | 1,171 | 10,453 | 8,755 | 2,589 | 2,048 |
Insulin-experienced | 0.35 (0.20) | 0.45 (0.27) | 0.35 (0.19) | 0.45 (0.23) | 0.36 (0.19) | 0.45 (0.24) |
n
| 244 | 201 | 2,163 | 1,812 | 766 | 585 |
Insulin-naïve | 0.28 (0.14) | 0.36 (0.18) | 0.24 (0.13) | 0.35 (0.18) | 0.23 (0.13) | 0.35 (0.19) |
n
| 1,157 | 970 | 8,290 | 6,943 | 1,823 | 1,463 |
All Hypoglycemia Events
Measurement | Proportion of patients with at least one event, % (event/person-year) | |||||
---|---|---|---|---|---|---|
Age ≤40 years | Age >40–65 years | Age >65 years | ||||
Baseline | 24 weeks | Baseline | 24 weeks | Baseline | 24 weeks | |
Hypoglycemia (overall) | ||||||
Entire cohort | 6.4 (1.89) | 3.3*** (0.91) | 7.3 (2.56) | 4.7*** (1.42) | 10.0 (3.75) | 6.6*** (1.88) |
n
| 1,467 | 1,279 | 10,967 | 9,677 | 2,807 | 2,334 |
Insulin-experienced | 16.3 (6.40) | 6.3*** (2.16) | 19.9 (7.98) | 6.0*** (1.69) | 23.9 (9.67) | 8.1*** (2.18) |
n
| 258 | 223 | 2,286 | 1,991 | 840 | 680 |
Insulin-naïve | 4.3 (0.92) | 2.7* (0.65) | 3.9 (1.13) | 4.4 (1.35) | 4.1 (1.22) | 6.0** (1.76) |
n
| 1,209 | 1,056 | 8,681 | 7,686 | 1,967 | 1,654 |
Sulfonylurea | 6.2 (1.57) | 3.0* (0.87) | 6.0 (1.91) | 4.9 (1.40) | 7.1 (2.69) | 7.1 (2.04) |
n
| 942 | 657 | 8,261 | 5,517 | 1,913 | 1,199 |
No sulfonylurea | 6.9 (2.45) | 3.5 (0.96) | 11.2 (4.53) | 4.5* (1.44) | 16.3 (6.02) | 6.2** (1.72) |
n
| 525 | 622 | 2,706 | 4,160 | 894 | 1,135 |
Hypoglycemia (major)a
| ||||||
Entire cohort | 0.8 (0.12) | 0** (0) | 1.1 (0.23) | 0.0*** (0.00) | 1.6 (0.37) | 0.0*** (0.01) |
Insulin-experienced | 3.5 (0.55) | 0** (0) | 3.5 (0.85) | 0.1*** (0.01) | 4.0 (1.02) | 0.1*** (0.02) |
Insulin-naïve | 0.2 (0.03) | 0 (0) | 0.4 (0.07) | 0.0*** (0.00) | 0.5 (0.09) | 0** (0) |
Hypoglycemia (nocturnal)a
| ||||||
Entire cohort | 3.1 (0.53) | 1.0*** (0.26) | 3.5 (0.81) | 1.7*** (0.41) | 4.5 (1.10) | 2.3*** (0.47) |
Insulin-experienced | 7.4 (1.51) | 2.7* (0.93) | 11.3 (2.84) | 1.7*** (0.42) | 12.3 (3.10) | 2.4*** (0.44) |
Insulin-naïve | 2.2 (0.32) | 0.7*** (0.12) | 1.5 (0.27) | 1.7 (0.41) | 1.2 (0.25) | 2.2* (0.48) |
Major Hypoglycemia Events
Nocturnal Hypoglycemia Events
SADRs
Body Weight
Measurement | Age ≤40 years | Age >40–65 years | Age >65 years | |||
---|---|---|---|---|---|---|
Baseline | Change after 24 weeks | Baseline | Change after 24 weeks | Baseline | Change after 24 weeks | |
HbA1c
| ||||||
Entire cohort | ||||||
% | 9.6 (1.7) | −2.3*** (1.7) | 9.5 (1.6) | −2.0*** (1.6) | 9.4 (1.8) | −1.8*** (1.7) |
mmol/mol | 81.4 (18.6) | −48.6*** (18.6) | 80.3 (17.5) | −45.4*** (17.5) | 79.2 (19.7) | −43.2*** (18.6) |
n
| 1,093 | 7,767 | 1,563 | |||
Insulin-experienced | ||||||
% | 9.3 (1.8) | −1.8*** (1.7) | 9.3 (1.7) | −1.7*** (1.7) | 9.2 (2.0) | −1.4*** (1.9) |
mmol/mol | 78.1 (19.7) | −43.2*** (18.6) | 78.1 (18.6) | −42.1*** (18.6) | 77.1 (21.9) | −38.8*** (20.8) |
n
| 183 | 1,492 | 409 | |||
Insulin-naïve | ||||||
% | 9.7 (1.7) | −2.4*** (1.7) | 9.5 (1.6) | −2.1*** (1.6) | 9.5 (1.7) | −1.9*** (1.6) |
mmol/mol | 82.5 (18.6) | −49.7*** (18.6) | 80.3 (17.5) | −46.5*** (17.5) | 80.3 (18.6) | −44.3*** (17.5) |
n
| 910 | 6,275 | 1,154 |
Baseline | 24 weeks | Baseline | 24 weeks | Baseline | 24 weeks | |
---|---|---|---|---|---|---|
% patients with HbA1c <7.0%a
| ||||||
Entire cohort | 1.8 | 33.9 | 2.5 | 31.6 | 5.6 | 29.5 |
n
| 1,318 | 1,166 | 9,451 | 8,421 | 2,179 | 1,849 |
Insulin-experienced | 3.9 | 30.3 | 5.2 | 30.9 | 10.9 | 28.7 |
n
| 229 | 195 | 1,883 | 1,667 | 626 | 499 |
Insulin-naïve | 1.4 | 34.6 | 1.9 | 31.8 | 3.5 | 29.9 |
n
| 1,089 | 971 | 7,568 | 6,754 | 1,553 | 1,350 |
Baseline | Change after 24 weeks | Baseline | Change after 24 weeks | Baseline | Change after 24 weeks | |
---|---|---|---|---|---|---|
FPG before breakfast (mmol/l, mg/dl) | ||||||
Entire cohort | 11.4 (3.4), | −4.4*** (3.2), | 10.9 (3.2), | −3.9*** (3.2), | 10.5 (3.5), | −3.4*** (3.7), |
205 (61) | −78*** (58) | 197 (58) | −70*** (59) | 190 (63) | −62*** (67) | |
n
| 1,043 | 7,823 | 1,726 | |||
Insulin-experienced | 10.7 (3.3), | −3.6*** (3.5), | 10.0 (3.3), | −2.7*** (3.4), | 9.3 (3.4), | −2.0*** (3.8), |
193 (59) | −65*** (63) | 179 (59) | −49*** (62) | 168 (61) | −36*** (68) | |
n
| 171 | 1,513 | 470 | |||
Insulin-naïve | 11.5 (3.4), | −4.5*** (3.2), | 11.2 (3.2), | −4.2*** (3.1), | 11.0 (3.4), | −4.0*** (3.6), |
207 (61) | −81*** (57) | 201 (57) | −75*** (57) | 198 (62) | −71*** (65) | |
n
| 872 | 6,310 | 1,256 | |||
PPG after breakfast (mmol/l, mg/dl) | ||||||
Entire cohort | 15.7 (4.3), | −6.2*** (4.2), | 14.8 (4.1), | −5.2*** (4.2), | 14.2 (4.4), | −4.0*** (4.7), |
283 (77) | −112*** (75) | 266 (75) | −94*** (75) | 255 (80) | −73*** (84) | |
n
| 680 | 5,348 | 1,029 | |||
Insulin-experienced | 14.3 (4.7), | −5.1*** (4.4), | 13.9 (4.2), | −4.0*** (4.2), | 13.2 (4.5), | −2.8*** (4.6) |
257 (84) | −92*** (80) | 250 (76) | −71*** (76) | 238 (81) | −50*** (83) | |
n
| 114 | 993 | 267 | |||
Insulin-naïve | 16.0 (4.2), | −6.5*** (4.1), | 15.0 (4.1), | −5.5*** (4.1), | 14.5 (4.4), | −4.5*** (4.6), |
288 (75) | −116*** (73) | 269 (74) | −99*** (74) | 261 (79) | −81*** (83) | |
n
| 566 | 4,355 | 762 | |||
Body weight (kg) | ||||||
Entire cohort | 77.3 (15.7) | −0.5*** (3.7) | 77.8 (16.4) | −0.5*** (4.0) | 70.5 (14.7) | 0.2* (3.7) |
n
| 1,166 | 8,603 | 2,012 | |||
Insulin-experienced | 80.1 (17.0) | −0.3 (3.9) | 77.7 (16.4) | −0.8*** (3.6) | 71.7 (14.8) | −0.5** (3.5) |
n
| 201 | 1,784 | 575 | |||
Insulin-naïve | 76.7 (15.4) | −0.6*** (3.7) | 77.8 (16.4) | −0.4*** (4.1) | 70.0 (14.6) | 0.4*** (3.7) |
n
| 965 | 6,819 | 1,437 | |||
HRQoL (UK VAS)b
| ||||||
Entire cohort | 0.625 (0.293) | 0.204*** (0.281) | 0.691 (0.261) | 0.149*** (0.258) | 0.680 (0.244) | 0.109*** (0.243) |
n
| 759 | 6,213 | 1,958 | |||
Insulin-experienced | 0.719 (0.265) | 0.141*** (0.265) | 0.723 (0.223) | 0.106*** (0.239) | 0.654 (0.245) | 0.113*** (0.243) |
n
| 119 | 1,276 | 575 | |||
Insulin-naïve | 0.608 (0.295) | 0.215*** (0.283) | 0.683 (0.270) | 0.160*** (0.261) | 0.691 (0.243) | 0.108*** (0.243) |
n
| 640 | 4,937 | 1,383 |