Steady state is reached within 2–3 days of once‐daily administration of degludec, a basal insulin with an ultralong duration of action

Heise, Tim; Korsatko, Stefan; Nosek, Leszek; Coester, Hans-Veit; Deller, Sigrid; Roepstorff, Carsten; Segel, Stine; Kapur, Rahul; Haahr, Hanne; Hompesch, Marcus

doi:10.1111/1753-0407.12266

Cited by 41 publications

(37 citation statements)

References 18 publications

(39 reference statements)

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“…An important prerequisite for a flatter and more stable glucose-lowering effect profile within a dosing interval is that a once-daily basal insulin has an action profile that extends substantially beyond 24 h. This is because, under SS conditions, the overlapping action of several injections decreases the peak-to-trough ratio [5]. Therefore, the long half-life of IDeg would be expected to lead to less fluctuation in insulin levels and glucose-lowering effect across the 24-h dosing interval [14,15], as shown in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, basal insulin analogs, such as insulin glargine (IGlar) and insulin detemir (IDet), while showing less peak effect than neutral protamine Hagedorn insulin, are still not peakless. Rather they are characterized by 24-h glucose-lowering effect profiles with periods of low action rising to a peak/plateau followed by a decline [3][4][5]. Furthermore, the within-patient variability of the glucose-lowering effect of IGlar was shown to be greater than IDet [6,7].…”

Section: Introductionmentioning

confidence: 98%

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Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine

Heise

Hövelmann

Nosek

et al. 2015

Expert Opinion on Drug Metabolism & Toxicology

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130

142

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine

Heise

Hövelmann

Nosek

et al. 2015

Expert Opinion on Drug Metabolism & Toxicology

Self Cite

130

142

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show abstract

“…As a consequence of the extended duration of action of IDeg, well beyond 24 h in all patients [41, 43], the glucose-lowering effect of IDeg builds up during the first days of once-daily dosing and reaches a plateau within 2–3 days [44]. For the same reason, the steady-state glucose-lowering effect of IDegAsp is increased compared with single-dose treatment.…”

Section: Pharmacodynamic Characteristics Of Idegaspmentioning

confidence: 99%

“…Thereafter, the exposure level of serum IDeg is unchanged from day to day (Fig. 6a) [44]. Second, in a multiple-dose regimen, the plateau levels of exposure and effect depend only on the total daily dose rather than the dosing frequency [49].…”

Section: Pharmacodynamic Characteristics Of Idegaspmentioning

confidence: 99%

“…Clinical steady state for IDeg is obtained within 2–3 days of once-daily IDeg dosing [44], and therefore it can be anticipated that also after 2–3 days of once-daily IDegAsp dosing, clinical steady state will occur for the basal IDeg component. In a multiple-dose study with IDegAsp in patients with T1DM, exposure of the IDeg component was evenly distributed across the 24-h dosing interval at steady state, as indicated by a mean ratio of AUC IDeg,0-12h,SS /AUC IDeg,τ,SS of 0.51 [9].…”

Section: Pharmacokinetic Characteristics Of Idegaspmentioning

confidence: 99%

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A Review of Insulin Degludec/Insulin Aspart: Pharmacokinetic and Pharmacodynamic Properties and Their Implications in Clinical Use

Fita

Heise

2016

Clin Pharmacokinet

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Insulin degludec/insulin aspart (IDegAsp; 70 % IDeg and 30 % IAsp) is a soluble combination of two individual insulin analogues in one product, designed to provide mealtime glycaemic control due to the IAsp component and basal glucose-lowering effect from the IDeg component. The pharmacokinetic and pharmacodynamic characteristics of IDegAsp have been investigated in a series of clinical pharmacology studies with generally comparable designs, methodologies and patient inclusion/exclusion criteria. The glucose-lowering effect profile of IDegAsp during once-daily dosing at steady state shows distinct and clearly separated action from the prandial and basal components of IDegAsp. The IAsp component provides rapid onset and peak glucose-lowering effect followed by a flat glucose-lowering effect lasting beyond 30 h due to IDeg. During twice-daily dosing, the distinct peak effect and the flat basal effect are retained following each dose. The pharmacological properties of IDegAsp are maintained in the elderly, children, adolescents, Japanese patients and those with hepatic or renal impairment. The potential clinical benefits associated with the pharmacological properties of IDegAsp have been verified in phase III clinical trials comparing IDegAsp with three other currently available treatment options: premixed insulin, basal-bolus regimens and basal-only therapy. IDegAsp shows favourable clinical benefits compared with biphasic insulin aspart 30 and is a viable alternative to basal-bolus and basal-only therapy. This review presents the results from clinical pharmacology studies conducted with IDegAsp to date, and extrapolates these results to clinical use of IDegAsp in the context of findings from the IDegAsp clinical therapeutic studies.

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Leveraging Clinical Pharmacology Data to Assess Biosimilarity and Interchangeability of Insulin Products

Vaidyanathan

Wang

Tran

et al. 2022

Clin Pharma and Therapeutics

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There is over a hundred years of clinical experience with insulin for the treatment of diabetes. The US Food and Drug Administration (FDA) approved the first insulin biosimilar interchangeable product in 2021 for improving glycemic control in adults and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Several recombinant insulin products are available in the United States, including the recently approved biosimilar insulins. The approval of the biosimilar insulin products was based on comparative analytical characterizations and comparative pharmacokinetic (PK) and pharmacodynamic (PD) data. The primary objective of this review is to discuss the scientific considerations in the demonstration of biosimilarity of a proposed insulin biosimilar to a reference product and the role of clinical pharmacology studies in the determination of biosimilarity and interchangeability. Euglycemic clamp studies are considered a “gold standard” for insulin PK and PD characterization and have been widely used to determine the time‐action profiles of rapid‐acting, intermediate‐acting, and long‐acting insulin products. Clinical pharmacology aspects of study design, including selection of appropriate dose, study population, PK, and PD end points, are presented. Finally, the role of clinical pharmacology studies in the interchangeability assessment of insulin and the regulatory pathways used for insulin and the experience with follow‐on insulins and the two recently approved biosimilar insulin products is discussed.

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Steady state is reached within 2–3 days of once‐daily administration of degludec, a basal insulin with an ultralong duration of action

Abstract: Serum IDeg concentrations reached steady state within 2-3 days of once-daily subcutaneous administration in all subjects with T1DM or T2DM, including elderly and African American and Hispanic/Latino subjects. At steady state, serum IDeg concentrations were unchanged from day to day.

Cited by 41 publications

References 18 publications

Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine

Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine

A Review of Insulin Degludec/Insulin Aspart: Pharmacokinetic and Pharmacodynamic Properties and Their Implications in Clinical Use

Leveraging Clinical Pharmacology Data to Assess Biosimilarity and Interchangeability of Insulin Products

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