In Silico Head-to-Head Comparison of Insulin Glargine 300 U/mL and Insulin Degludec 100 U/mL in Type 1 Diabetes

被引:18
作者
Schiavon, Michele [1 ]
Visentin, Roberto [1 ]
Giegerich, Clemens [2 ]
Sieber, Jochen [3 ]
Dalla Man, Chiara [1 ]
Cobelli, Claudio [1 ]
Klabunde, Thomas [2 ]
机构
[1] Univ Padua, Dept Informat Engn, Padua, Italy
[2] Sanofi Aventis Deutschland GmbH, Translat Dis Modeling, R&D Digital & Data Sci, Ind Pk Hochst, D-65926 Frankfurt, Germany
[3] Becton Dickinson & Co, Med Affairs Diabet Care EMEA, Franklin Lakes, NJ USA
关键词
Basal insulin; Mathematical modeling; Pharmacokinetics; Pharmacodynamics; Virtual trial; BASAL INSULIN; DAY VARIABILITY; PROFILES; PHARMACODYNAMICS; PROTRACTION; PROVIDES; ANALOGS; PHASE-3; ASPART; MODEL;
D O I
10.1089/dia.2020.0027
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Second-generation long-acting insulin glargine 300 U/mL (Gla-300) and degludec 100 U/mL (Deg-100) provide novel basal insulin therapies for the treatment of type 1 diabetes (T1D). Both offer a flatter pharmacokinetic (PK) profile than the previous generation of long-acting insulins, thus improving glycemic control while reducing hypoglycemic events. This work describes an in silico head-to-head comparison of the two basal insulins on 24-h glucose profiles and was used to guide the design of a clinical trial. Materials and Methods: The Universities of Virginia (UVA)/Padova T1D simulator describes the intra-/interday variability of glucose-insulin dynamics and thus provides a robust bench-test for assessing glucose control for basal insulin therapies. A PK model describing subcutaneous absorption of Deg-100, in addition to the one already available for Gla-300, has been developed based on T1D clinical data and incorporated into the simulator. One hundred in silico T1D subjects received a basal insulin dose (Gla-300 or Deg-100) for 12 weeks (8 weeks uptitration, 4 weeks stable dosing) by morning or evening administration in a basal/bolus regimen. The virtual patients were uptitrated to their individual doses with two different titration rules. Results: The last 2-week simulated continuous glucose monitoring data were used to calculate various outcome metrics for both basal insulin treatments, with primary outcome being the percent time in glucose target (70-140 mg/dL). The simulations show no statistically significant difference for Gla-300 versus Deg-100 in the main endpoints. Conclusions: This work suggests comparable glucose control using either Gla-300 or Deg-100 and was used to guide the design of a clinical trial intended to compare second-generation long-acting insulin analogues.
引用
收藏
页码:553 / 561
页数:9
相关论文
共 40 条
[1]  
[Anonymous], J DIABETES SCI TECHN
[2]  
[Anonymous], COMPUTATIONAL MATH M
[3]  
[Anonymous], MATLAB VERS 9 1 0 44
[4]   Morning administration of 0.4 U/kg/day insulin glargine 300 U/mL provides less fluctuating 24-hour pharmacodynamics and more even pharmacokinetic profiles compared with insulin degludec 100 U/mL in type 1 diabetes [J].
Bailey, T. S. ;
Pettus, J. ;
Roussel, R. ;
Schmider, W. ;
Maroccia, M. ;
Nassr, N. ;
Klein, O. ;
Bolli, G. B. ;
Dahmen, R. .
DIABETES & METABOLISM, 2018, 44 (01) :15-21
[5]   Low within- and between-day variability in exposure to new insulin glargine 300 U/ml [J].
Becker, R. H. A. ;
Nowotny, I. ;
Teichert, L. ;
Bergmann, K. ;
Kapitza, C. .
DIABETES OBESITY & METABOLISM, 2015, 17 (03) :261-267
[6]   New Insulin Glargine 300 Units.mL-1 Provides a More Even Activity Profile and Prolonged Glycemic Control at Steady State Compared With Insulin Glargine 100 Units.mL-1 [J].
Becker, Reinhard H. A. ;
Dahmen, Raphael ;
Bergmann, Karin ;
Lehmann, Anne ;
Jax, Thomas ;
Heise, Tim .
DIABETES CARE, 2015, 38 (04) :637-643
[7]   Comparison of Insulin Glargine 300 Units/mL and 100 Units/mL in Adults With Type 1 Diabetes: Continuous Glucose Monitoring Profiles and Variability Using Morning or Evening Injections [J].
Bergenstal, RichardM. ;
Bailey, Timothy S. ;
Rodbard, David ;
Ziemen, Monika ;
Guo, Hailing ;
Muehlen-Bartmer, Isabel ;
Ahmann, Andrew J. .
DIABETES CARE, 2017, 40 (04) :554-560
[8]  
Cobelli C, 2019, INTRO MODELING METAB
[9]   Artificial Pancreas Past, Present, Future [J].
Cobelli, Claudio ;
Renard, Eric ;
Kovatchev, Boris .
DIABETES, 2011, 60 (11) :2672-2682
[10]   International Consensus on Use of Continuous Glucose Monitoring [J].
Danne, Thomas ;
Nimri, Revital ;
Battelino, Tadej ;
Bergenstal, Richard M. ;
Close, Kelly L. ;
DeVries, J. Hans ;
Garg, Satish ;
Heinemann, Lutz ;
Hirsch, Irl ;
Amiel, Stephanie A. ;
Beck, Roy ;
Bosi, Emanuele ;
Buckingham, Bruce ;
Cobelli, Claudio ;
Dassau, Eyal ;
Doyle, Francis J., III ;
Heller, Simon ;
Hovorka, Roman ;
Jia, Weiping ;
Jones, Tim ;
Kordonouri, Olga ;
Kovatchev, Boris ;
Kowalski, Aaron ;
Laffel, Lori ;
Maahs, David ;
Murphy, Helen R. ;
Norgaard, Kirsten ;
Parkin, Christopher G. ;
Renard, Eric ;
Saboo, Banshi ;
Scharf, Mauro ;
Tamborlane, William V. ;
Weinzimer, Stuart A. ;
Phillip, Moshe .
DIABETES CARE, 2017, 40 (12) :1631-1640