Subcutaneous Injection Depth Does Not Affect the Pharmacokinetics or Glucodynamics of Insulin Lispro in Normal Weight or Healthy Obese Subjects

Peña, Amparo de la; Yeo, Kwee Poo; Linnebjerg, Helle; Catton, Edward; Reddy, Shobha; Brown‐Augsburger, Patricia; Morrow, Linda; Ignaut, Debra A.

doi:10.1177/1932296815573865

Cited by 15 publications

(11 citation statements)

References 13 publications

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“…Overall, the behavior of the insulin profiles are in agreement with published data in terms of time to peak concentrations and overall duration of exposures for insulin lispro 100 U/mL, human regular insulin 100 U/mL, human regular insulin 500 U/mL, insulin mixes, and NPH (Figure ). Similarly, model‐simulated profiles of insulin lispro 200 U/mL and insulin glargine (Lantus ® ) predicted from insulin lispro 100 U/mL and Basaglar ® were confirmed to be comparable with their respective observed time‐action profiles (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Modeling Pharmacokinetic Profiles of Insulin Regimens to Enhance Understanding of Subcutaneous Insulin Regimens

Tham

Schneck

Ertekin³

et al. 2017

The Journal of Clinical Pharmacology

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Insulin pharmacokinetics following subcutaneous administration were modeled, simulated, and displayed through an interactive and user‐friendly interface to illustrate the time course of administered insulins frequently prescribed, providing a simple tool for clinicians through a straightforward visualization of insulin regimens. Pharmacokinetic data of insulin formulations with different onset and duration of action from several clinical studies, including insulin glargine, regular insulin, neutral protamine Hagedorn (NPH), insulin lispro, and premixed preparations of NPH with regular insulin (Mix 70/30), and insulin lispro protamine suspension with insulin lispro (Mix 50/50, Mix 75/25), were used to develop a predictive population pharmacokinetic model of insulins with consideration of factors such as insulin formulation, weight‐based dosing, body‐weight effect on volume of distribution, and administration time relative to meals, on the insulin time‐action profile. The model‐predicted insulin profile of each insulin was validated and confirmed to be comparable to observed data via an external validation method. Model‐based simulations of clinically relevant insulin‐dosing scenarios to cater to specific initial patient and prescribing conditions were then implemented with differential equations using the R statistical program (version 3.2.2). The R package Shiny was subsequently applied to build a web browser interface to execute and visualize the model simulation outputs. The application of insulin pharmacokinetic modeling enabled informative visualization of insulin time‐action profiles and provided an efficient and intuitive educational tool to quickly convey and interactively explore many insulin time‐action profiles to ease the understanding of insulin formulations in clinical practice.

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Section: Resultsmentioning

confidence: 99%

Modeling Pharmacokinetic Profiles of Insulin Regimens to Enhance Understanding of Subcutaneous Insulin Regimens

Tham

Schneck

Ertekin³

et al. 2017

The Journal of Clinical Pharmacology

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“…Hirose et al [ 31 ] conducted pharmacokinetic/pharmacodynamic (PK/PD) studies and determined bioequivalent maximum concentrations and similar areas under the curve for the 4-, 6- and 8-mm needles. A crossover study using the euglycemic clamp measuring PK/PD in both normal-weight and obese, healthy adults showed similar insulin uptake and action when insulin lispro was injected with a 5-mm needle on 1 day and an 8-mm needle on the next day [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Turkish Insulin Injection Technique Study: Population Characteristics of Turkish Patients with Diabetes Who Inject Insulin and Details of Their Injection Practices as Assessed by Survey Questionnaire

et al. 2018

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IntroductionOver 7 million people in Turkey have diabetes. Of the 1 million who inject insulin little is known of their habits and injection techniques.MethodsWe conducted an Injection Technique Questionnaire (ITQ) survey throughout Turkey that involved 1376 patients from 56 centers. Turkish values were compared with those from 41 other countries participating in the ITQ, known here as Rest of World (ROW).ResultsThe majority (50.4%) of Turkish insulin users give four injections/ day as opposed to ROW, where only 30.9% do. The abdomen is the most common injection site used by Turkish patients, but they also inject insulin in multiple body sites more often than do patients in ROW. Body mass index values in Turkey were 0.75 units higher than those in ROW as was the mean total daily dose (average daily dose [ADD]) of insulin (54.0 IU in Turkey vs. 47.4 IU in ROW). Mean glycated hemoglobin (HbA1c) in Turkey was 9.1%, which is higher than in ROW and possibly related to the higher BMI and ADD. Turkish patients use insulin analogs (short and long-acting) more frequently than do patients in ROW. The shortest pen needles (4 mm) are used by about one-third of patients in Turkey, but the longer ones (8 mm) are equally common. Needles are reused in Turkey at a rate of 3.4 injections/single needle. However, needle reuse, whether with pens or syringes, is lower in Turkey than ROW, as is the number of times a reused needle is used. More than 75% of used sharps in Turkey go into the rubbish, with nearly 6% having no protection of the tip.ConclusionThe continued use of 8-mm needles raises the risk of intramuscular injections in Turkish patients. Despite full reimbursement, needle reuse still remains an important issue. More focus needs to be given to dwell times under the skin, reconstitution of cloudy insulant, correct use of skin folds and safe disposal of sharps.FundingBD Diabetes Care.

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“…Insulin pharmacokinetics/pharmacodynamics has been shown to be the same when injected into resting individuals using short and long needles. 27,38,39 A summary of these needle length and insulin absorption studies is presented in Supplemental Appendix 3 (available online at http://www.mayoclinicproceedings. org).…”

Section: Needle Lengthmentioning

confidence: 99%

New Insulin Delivery Recommendations

Frid

Kreugel

Grassi

et al. 2016

Mayo Clinic Proceedings

234

278

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Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes.

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Subcutaneous Injection Depth Does Not Affect the Pharmacokinetics or Glucodynamics of Insulin Lispro in Normal Weight or Healthy Obese Subjects

Cited by 15 publications

References 13 publications

Modeling Pharmacokinetic Profiles of Insulin Regimens to Enhance Understanding of Subcutaneous Insulin Regimens

Modeling Pharmacokinetic Profiles of Insulin Regimens to Enhance Understanding of Subcutaneous Insulin Regimens

Turkish Insulin Injection Technique Study: Population Characteristics of Turkish Patients with Diabetes Who Inject Insulin and Details of Their Injection Practices as Assessed by Survey Questionnaire

New Insulin Delivery Recommendations

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