Pharmacodynamic Evaluation: Diabetes Methodologies

Becker, R. H. A.

doi:10.1007/978-3-540-89891-7_33

Cited by 13 publications

(11 citation statements)

References 116 publications

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“…The hyperinsulin euglycemic clamp is regarded as the gold standard for insulin sensitivity evaluation 11 , 12 . Further, it is widely accepted and used to investigate the PK/PD of insulin preparations 13 – 15 . The quality of the euglycemic clamp is of great importance because it is related to the accuracy of the assessment of PK/PD 16 .…”

Section: Discussionmentioning

confidence: 99%

Similar pharmacokinetics and pharmacodynamics of a new biosimilar and reference insulin aspart in healthy Chinese males

Hui

Sun

et al. 2021

Sci Rep

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Insulin aspart (IAsp) is one of the main therapies used to control blood glucose after a meal. This study aimed to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 rapid-acting IAsp products: a new IAsp biosimilar (RD10046) and NovoRapid. In a single-center, randomized, single-dose, 2-period, crossover, euglycemic clamp study (registry number: CTR20180517, registration date: 2018-05-30), healthy Chinese males were randomized to receive 0.2 U/kg of the IAsp biosimilar RD10046 and NovoRapid under fasted conditions on two separate occasions. PK and PD were assessed for up to 10 h. Of the 30 randomized subjects, all 30 completed both treatment periods. The PK (area under the curve [AUC] of total IAsp; maximum observed IAsp concentration [Cmax]) and PD (maximum glucose infusion rate [GIRmax]; total glucose infusion during the clamp [AUCGIR,0–10h]) were similar between the new IAsp biosimilar RD10046 and NovoRapid. In all cases, the 90% CIs for the ratios of the geometric means were completely contained in the prespecified acceptance limits of 0.80–1.25. No hypoglycemic events, allergic reactions, or local injection adverse reactions occurred in this trial. We concluded that the studied IAsp biosimilar (RD10046) was bioequivalent to NovoRapid.

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Section: Discussionmentioning

confidence: 99%

Similar pharmacokinetics and pharmacodynamics of a new biosimilar and reference insulin aspart in healthy Chinese males

Hui

Sun

et al. 2021

Sci Rep

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“…Our study not only had higher statistical power due to the larger sample size, it also used the euglycemic glucose clamp technique as a state-of-the-art method for the assessment of insulin PD (17), which has higher precision than meal tests. Furthermore, we replicated injections into LHT and NAT during the clamp tests, which further increased statistical power and permitted determination of intrasubject variability.…”

Section: Discussionmentioning

confidence: 99%

Insulin Injection Into Lipohypertrophic Tissue: Blunted and More Variable Insulin Absorption and Action and Impaired Postprandial Glucose Control

et al. 2016

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“…The principle of the PD glucose clamp is quite simple: the blood glucose (BG)‐lowering effect of an insulin is antagonized by glucose infused at a variable rate, so that BG is “clamped” at a predefined target (the term “hyperinsulinaemic” is used to indicate that serum insulin concentrations induced by the exogenous are supra‐physiological to induce a BG‐lowering effect). In manual clamps, the investigator performs BG measurements and manually adjusts glucose infusion rates (GIRs) every 3‐10 minutes, whereas in automated clamps, BG is measured continuously and GIR is adapted every minute by an implemented algorithm (and therefore with minimized potential bias).…”

Section: Glucose Clamp Studies: Principle and Basic Considerationsmentioning

confidence: 99%

“…The hyperinsulinaemic‐euglycaemic glucose clamp, originally designed for the assessment of insulin sensitivity, quickly became the “gold standard” for the assessment of pharmacodynamic (PD) characteristics of insulin preparations more than 25 years ago, and regulatory guidelines required glucose clamp results for the development of new insulin preparations . The value of glucose clamps for PD assessments per se had not been questioned until recently, when two commentaries queried the suitability of the glucose clamp technique for the demonstration of bioequivalence between insulin preparations because of alleged methodological shortcomings .…”

Section: Introductionmentioning

confidence: 99%

Euglycaemic glucose clamp: what it can and cannot do, and how to do it

Heise

Zijlstra

Nosek

et al. 2016

Diabetes Obesity Metabolism

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The hyperinsulinaemic-euglycaemic glucose clamp has always been regarded as the "gold standard" for the assessment of pharmacodynamic (PD) properties of insulin preparations; however, there has been controversy over a variety of methodogical details, such as study population, dosing time and the initial stabilization of blood glucose (BG) concentrations at the clamp target level, among clamp groups. As the impact of these details on PD results is unclear, the present review provides an overview of different methodological approaches for both the man- However, even before this, clamp experts had discussed and sometimes disagreed on methodological details, 5 making it difficult to assess the PD results of glucose clamp studies for non-experts, particularly when these results differed between clamp groups. It might therefore be time to review both the strengths and the limitations of the clamp technique, addressing the most important methodological issues and discussing their potential impact on PD outcomes. | GLUCOSE CLAMP STUDIES: PRINCIPLE AND BASIC CONSIDERATIONSThe principle of the PD glucose clamp is quite simple 1 : the blood glucose (BG)-lowering effect of an insulin is antagonized by glucose

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Pharmacodynamic Evaluation: Diabetes Methodologies

Cited by 13 publications

References 116 publications

Similar pharmacokinetics and pharmacodynamics of a new biosimilar and reference insulin aspart in healthy Chinese males

Similar pharmacokinetics and pharmacodynamics of a new biosimilar and reference insulin aspart in healthy Chinese males

Insulin Injection Into Lipohypertrophic Tissue: Blunted and More Variable Insulin Absorption and Action and Impaired Postprandial Glucose Control

Euglycaemic glucose clamp: what it can and cannot do, and how to do it

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