Insulin stacking versus therapeutic accumulation: Understanding the differences

Tim Heise, Luigi Meneghini

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Objective: The build-up in insulin levels following repeated injection of prandial insulin at close intervals - referred to as insulin stacking - can increase the risk of hypoglycemia. With the development of basal insulins with a half-life >24 hours and a duration of action >40 hours, clinicians may be concerned about stacking when these long-Acting formulations are administered once daily. The objective of this review is to clarify the difference between inappropriate insulin stacking when shorter-Acting insulin formulations are repeatedly used to correct hyperglycemia and the appropriate accumulation of long-Acting insulin formulations dosed to steady-state pharmacokinetic (PK) profiles.Methods: Relevant literature on insulin stacking, glucose-clamp studies, and clinical studies of insulin, in conjunction with the clinical experience of the authors, were used to present an overview of insulin PK properties and the effects of appropriate and inappropriate dosing intervals on steady-state conditions and likely clinical outcomes.Results: Clinical studies confirm theoretical PK principles showing that unwanted insulin stacking (excessive concentrations) for basal insulin can be avoided by following recommended dosing and titration algorithms. Long-Acting basal insulins need more time to reach steady state than shorter-Acting basal insulins but then show reduced peak-trough fluctuations, translating into more consistent biologic action over a 24-hour period.Conclusion: The unwanted stacking and consequent hypoglycemia that can occur when correctional doses of rapid-Acting insulin are administered at close intervals does not occur when long-Acting basal insulins are dosed in appropriate amounts and adjusted at appropriate time intervals (e.g., insulin stacking, insulin administration, diabetes, ultralong duration of action, hypoglycemia every three or more days), allowing for pharmacologic steady-state accumulation

Original languageEnglish (US)
Pages (from-to)75-83
Number of pages9
JournalEndocrine Practice
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

Insulin
Long-Acting Insulin
Short-Acting Insulin
Hypoglycemia
Therapeutics
Pharmacokinetics
Insulins
Glucose Clamp Technique
Hyperglycemia
Half-Life
Meals
Injections

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Insulin stacking versus therapeutic accumulation : Understanding the differences. / Heise, Tim; Meneghini, Luigi.

In: Endocrine Practice, Vol. 20, No. 1, 01.01.2014, p. 75-83.

Research output: Contribution to journalArticle

@article{40b64626a4da4aa0a04bec61ec25c624,
title = "Insulin stacking versus therapeutic accumulation: Understanding the differences",
abstract = "Objective: The build-up in insulin levels following repeated injection of prandial insulin at close intervals - referred to as insulin stacking - can increase the risk of hypoglycemia. With the development of basal insulins with a half-life >24 hours and a duration of action >40 hours, clinicians may be concerned about stacking when these long-Acting formulations are administered once daily. The objective of this review is to clarify the difference between inappropriate insulin stacking when shorter-Acting insulin formulations are repeatedly used to correct hyperglycemia and the appropriate accumulation of long-Acting insulin formulations dosed to steady-state pharmacokinetic (PK) profiles.Methods: Relevant literature on insulin stacking, glucose-clamp studies, and clinical studies of insulin, in conjunction with the clinical experience of the authors, were used to present an overview of insulin PK properties and the effects of appropriate and inappropriate dosing intervals on steady-state conditions and likely clinical outcomes.Results: Clinical studies confirm theoretical PK principles showing that unwanted insulin stacking (excessive concentrations) for basal insulin can be avoided by following recommended dosing and titration algorithms. Long-Acting basal insulins need more time to reach steady state than shorter-Acting basal insulins but then show reduced peak-trough fluctuations, translating into more consistent biologic action over a 24-hour period.Conclusion: The unwanted stacking and consequent hypoglycemia that can occur when correctional doses of rapid-Acting insulin are administered at close intervals does not occur when long-Acting basal insulins are dosed in appropriate amounts and adjusted at appropriate time intervals (e.g., insulin stacking, insulin administration, diabetes, ultralong duration of action, hypoglycemia every three or more days), allowing for pharmacologic steady-state accumulation",
author = "Tim Heise and Luigi Meneghini",
year = "2014",
month = "1",
day = "1",
doi = "10.4158/EP13090.RA",
language = "English (US)",
volume = "20",
pages = "75--83",
journal = "Endocrine Practice",
issn = "1530-891X",
publisher = "American Association of Clinical Endocrinology",
number = "1",

}

TY - JOUR

T1 - Insulin stacking versus therapeutic accumulation

T2 - Understanding the differences

AU - Heise, Tim

AU - Meneghini, Luigi

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Objective: The build-up in insulin levels following repeated injection of prandial insulin at close intervals - referred to as insulin stacking - can increase the risk of hypoglycemia. With the development of basal insulins with a half-life >24 hours and a duration of action >40 hours, clinicians may be concerned about stacking when these long-Acting formulations are administered once daily. The objective of this review is to clarify the difference between inappropriate insulin stacking when shorter-Acting insulin formulations are repeatedly used to correct hyperglycemia and the appropriate accumulation of long-Acting insulin formulations dosed to steady-state pharmacokinetic (PK) profiles.Methods: Relevant literature on insulin stacking, glucose-clamp studies, and clinical studies of insulin, in conjunction with the clinical experience of the authors, were used to present an overview of insulin PK properties and the effects of appropriate and inappropriate dosing intervals on steady-state conditions and likely clinical outcomes.Results: Clinical studies confirm theoretical PK principles showing that unwanted insulin stacking (excessive concentrations) for basal insulin can be avoided by following recommended dosing and titration algorithms. Long-Acting basal insulins need more time to reach steady state than shorter-Acting basal insulins but then show reduced peak-trough fluctuations, translating into more consistent biologic action over a 24-hour period.Conclusion: The unwanted stacking and consequent hypoglycemia that can occur when correctional doses of rapid-Acting insulin are administered at close intervals does not occur when long-Acting basal insulins are dosed in appropriate amounts and adjusted at appropriate time intervals (e.g., insulin stacking, insulin administration, diabetes, ultralong duration of action, hypoglycemia every three or more days), allowing for pharmacologic steady-state accumulation

AB - Objective: The build-up in insulin levels following repeated injection of prandial insulin at close intervals - referred to as insulin stacking - can increase the risk of hypoglycemia. With the development of basal insulins with a half-life >24 hours and a duration of action >40 hours, clinicians may be concerned about stacking when these long-Acting formulations are administered once daily. The objective of this review is to clarify the difference between inappropriate insulin stacking when shorter-Acting insulin formulations are repeatedly used to correct hyperglycemia and the appropriate accumulation of long-Acting insulin formulations dosed to steady-state pharmacokinetic (PK) profiles.Methods: Relevant literature on insulin stacking, glucose-clamp studies, and clinical studies of insulin, in conjunction with the clinical experience of the authors, were used to present an overview of insulin PK properties and the effects of appropriate and inappropriate dosing intervals on steady-state conditions and likely clinical outcomes.Results: Clinical studies confirm theoretical PK principles showing that unwanted insulin stacking (excessive concentrations) for basal insulin can be avoided by following recommended dosing and titration algorithms. Long-Acting basal insulins need more time to reach steady state than shorter-Acting basal insulins but then show reduced peak-trough fluctuations, translating into more consistent biologic action over a 24-hour period.Conclusion: The unwanted stacking and consequent hypoglycemia that can occur when correctional doses of rapid-Acting insulin are administered at close intervals does not occur when long-Acting basal insulins are dosed in appropriate amounts and adjusted at appropriate time intervals (e.g., insulin stacking, insulin administration, diabetes, ultralong duration of action, hypoglycemia every three or more days), allowing for pharmacologic steady-state accumulation

UR - http://www.scopus.com/inward/record.url?scp=84892724602&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892724602&partnerID=8YFLogxK

U2 - 10.4158/EP13090.RA

DO - 10.4158/EP13090.RA

M3 - Article

C2 - 24013982

AN - SCOPUS:84892724602

VL - 20

SP - 75

EP - 83

JO - Endocrine Practice

JF - Endocrine Practice

SN - 1530-891X

IS - 1

ER -