Steady-state pharmacokinetics and glucodynamics of the novel, long-acting basal insulin LY2605541 dosed once-daily in patients with type 2 diabetes mellitus

2013 ◽  
Vol 16 (4) ◽  
pp. 344-350 ◽  
Author(s):  
V. P. Sinha ◽  
D. C. Howey ◽  
S. L. Choi ◽  
K. F. Mace ◽  
T. Heise
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Steady State ◽  
Basal Insulin ◽  
The Novel ◽  
Once Daily ◽  
Long Acting

scholarly journals Population Pharmacokinetic/Pharmacodynamic Analysis of the DPP-4 Inhibitor Linagliptin in Japanese Patients with Type 2 Diabetes Mellitus

2013 ◽  
Vol 16 (5) ◽  
pp. 708 ◽  
Author(s):  
Yusuke Tadayasu ◽  
Akiko Sarashina ◽  
Yasuhiro Tsuda ◽  
Shinji Tatami ◽  
Christian Friedrich ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Steady State ◽  
Plasma Concentration ◽  
Therapeutic Dose ◽  
Dose Group ◽  
Japanese Patients ◽  
Once Daily

[Objectives] Linagliptin is a novel, highly selective and long acting DPP-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). Linagliptin exhibits non-linear pharmacokinetics (PK) due to saturable binding to plasma and tissue DPP-4. The aim of this study was to characterize the PK and PK/DPP-4 inhibition relationship of linagliptin in Japanese patients with T2DM using a population PK/DPP-4 model and to support the rationale for the therapeutic dose in Japanese patients by simulation. [Methods] Linagliptin plasma concentration and DPP-4 inhibition measurements from a placebo-controlled, parallel group multiple (28 days) dose trial that included 36 T2DM patients (18 patients each in 2.5 mg and 10 mg dose group) were used for analysis. Modeling was performed using FOCE INTERACTION estimation method implemented in NONMEM V. The linagliptin plasma concentration- and DPP-4 inhibition- time profiles were simulated for Japanese patients receiving 5 mg linagliptin once daily by the model established. [Results] Nonlinear PK of linagliptin in T2DM patients were well described by a 2-compartment model assuming concentration-dependent binding to DPP-4 in the central and peripheral compartment. Plasma DPP-4 inhibition was integrated in the model by relating the model-predicted DPP-4 occupancy with linagliptin linearly to DPP-4 inhibition. The simulation predicted that for the 5 mg dose group the trough DPP-4 inhibition at steady-state was 84.2%, which is higher than the target inhibition (≥80%) for an effective dose of DPP-4 inhibitor. In 2.5 mg dose group, steady-state DPP-4 inhibition of >80% was not maintained over 24 hours (observed and simulated). [Conclusions] The nonlinear PK of linagliptin and its plasma DPP-4 inhibition in patients were well characterized by a target-mediated drug disposition model relating DPP-4 occupancy with linagliptin to DPP-4 inhibition. Simulations of plasma DPP-4 inhibition suggest that 5 mg linagliptin once daily is an appropriate therapeutic dose for Japanese patients with T2DM.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

The Comparative Dosing and Glycemic Control of Intermediate and Long-Acting Insulins in Adult Patients With Type 1 and 2 Diabetes Mellitus

2021 ◽  
pp. 875512252110557
Author(s):  
Anna Kabakov ◽  
Andrew Merker
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Type 1 Diabetes Mellitus ◽  
Basal Insulin ◽  
Long Acting

Objective: The various basal insulin products possess differences in pharmacokinetics that can significantly impact glycemic control and total daily basal insulin dosing. In addition, there will be instances where transitions between the different long-acting insulins will need to be made. Because every basal insulin product is not interchangeable on a 1:1 unit-to-unit basis, it is important for health care providers to understand the expected dose adjustments necessary to maintain a similar level of glycemic control. Data Sources: A Medline and Web of Science search was conducted in September 2021 using the following keywords and medical subjecting headings: NPH, glargine, detemir, type 1 diabetes mellitus, and type 2 diabetes mellitus. Study Selection and Data Extraction: Included articles were those that followed adult patients with type 1 diabetes mellitus and/or type 2 diabetes mellitus and compared the following types of insulin: “NPH and glargine,” “NPH and detemir,” and “glargine and detemir” for at least 4 weeks, had documented basal insulin (BI) doses, and excluded pregnant patients. Data synthesis: Twenty-five articles were found that include adult type 1 and/or type 2 diabetes mellitus patients. Once daily NPH can be converted unit-to-unit to glargine or detemir. Twice daily NPH converted to glargine or detemir requires an initial 20% reduction in BI dose. An increase in dose of BI is recommended when transitioning from glargine to detemir. Glargine and detemir consistently resulted in improved glycemic control with lower incidence of hypoglycemic events compared with NPH. Conclusions: When transitioning between long-acting insulins, the doses are not always interchangeable on a 1:1 basis. Unit dose adjustments are likely if transitioning between BIs and can influence short-term parameters in the acute care setting and long-term parameters in the outpatient setting.

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