This is the first trial to describe the pharmacokinetic properties of liraglutide as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). |
Based on data obtained at steady-state, pharmacokinetic properties were comparable with those previously observed in healthy volunteers and subjects with type 2 diabetes mellitus. Pharmacokinetic endpoints derived from liraglutide concentration–time curves after the last dose were consistent with dose proportionality. |
These results add to the clinical profile of liraglutide in T1D. The efficacy and safety of liraglutide as adjunct therapy to insulin in this population have also been evaluated in three phase III trials (http://www.clinicaltrials.gov; NCT02098395, NCT01836523, NCT02092896) and one phase IV trial (NCT01612468). |
1 Introduction
2 Materials and Methods
2.1 Participants
2.2 Trial Design
2.3 Pharmacokinetic Assessments and Statistical Analysis
3 Results
3.1 Demographics
Liraglutide 0.6 mg [n = 14] | Liraglutide 1.2 mg [n = 13] | Liraglutide 1.8 mg [n = 13] | Liraglutide All doses [n = 40] | |
---|---|---|---|---|
Males/females [n (%)] | 8 (57)/6 (43) | 10 (77)/3(23) | 8 (62)/5 (38) | 26 (65)/14 (35) |
Age, years [range] | 38.1 (11.2) [20.0–55.0] | 34.3 (12.9) [20.0–55.0] | 32.4 (8.8) [18.0–45.0] | 35.0 (11.1) [18.0–55.0] |
Body weight, kg [range] | 75.2 (14.4) [55.7–91.4] | 72.3 (9.6) [57.5–86.1] | 74.6 (10.4) [60.0–89.8] | 74.1 (11.5) [55.7–91.4] |
BMI, kg/m2 [range] | 24.0 (2.7) [20.2–28.2] | 23.1 (2.1) [20.2–26.2] | 24.5 (2.4) [20.5–28.0] | 23.9 (2.4) [20.2–28.2] |
Duration of diabetes, years [range] | 18.5 (8.9) [6.4–33.9] | 18.6 (10.7) [6.7–43.8] | 15.4 (9.1) [1.9–33.7] | 17.5 (9.5) [1.9–43.8] |
Serum creatinine, μmol/L [range] | 74.8 (14.2) [52.0–97.0] | 85.2 (20.0) [54.0–117.0] | 74.5 (8.7) [58.0–92.0] | 78.1 (15.5) [52.0–117.0] |
3.2 Pharmacokinetics
Liraglutide 0.6 mg [n = 14] | Liraglutide 1.2 mg [n = 13] | Liraglutide 1.8 mg [n = 13] | Liraglutide All doses [n = 40] | |
---|---|---|---|---|
AUC0–24 h, pmol h/L | 181,464 (33) | 384,151 (20) | 569,771 (26) | – |
C
max, pmol/L | 9257 (33) | 20,067 (18) | 29,751 (28) | – |
C
trough, pmol/L | 5209 (43) | 13,051 (20) | 18,287 (32) | – |
t
max, h | 9 | 8 | 10 | 10 |
t
½, h | 15.3 (15.6) | 16.4 (135.2) | 18.8 (144.1) | 16.7 (128.8) |
CL/F, L/h | 0.88 (28.4) | 0.83 (18.2) | 0.84 (23.4) | 0.85 (23.6) |
V
z/F, L | 27.0 (36.2) | 26.0 (88.1) | 29.3 (120.2) | 27.4 (95.4) |