Two Treatment Approaches for Human Regular U-500 Insulin in Patients With Type 2 Diabetes not Achieving Adequate Glycemic Control on High-Dose U-100 Insulin Therapy With or Without Oral Agents: A Randomized, Titration-To-Target Clinical Trial

Hood, Robert C.; Arakaki, Richard; Wysham, Carol; Li, Ying G.; Settles, Julie; Jackson, Jeffrey A.

doi:10.4158/ep15612.or

Cited by 54 publications

(124 citation statements)

References 37 publications

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“…It is here that concentrated insulins, such as Eli Lilly’s U-500 concentrated insulin, have shown clinical benefit. Equivalent doses of more concentrated insulins often yield superior clinical results 66,67…”

Section: Resultsmentioning

confidence: 99%

rDNA insulin glargine U300 – a critical appraisal

Wang¹,

Zassman²,

Goldberg³

2016

DMSO

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BackgroundAs the first once-daily basal insulin analog, insulin glargine 100 U/mL (Gla-100; Lantus®) rapidly evolved into the most commonly prescribed insulin therapy worldwide. However, this insulin has clinical limitations. The approval of new basal insulin analogs in 2015 has already started to alter the prescribing landscape.ObjectiveTo review the available evidence on the clinical efficacy and safety of a more concentrated insulin glargine (recombinant DNA origin) injection 300 U/mL (Gla-300) compared to insulin Gla-100 in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM).MethodsThe following electronic databases were searched: PubMed and MEDLINE (using Ovid platform), Scopus, BIOSIS, and Google Scholar through June 2016. Conference proceedings of the American Diabetes Association (2015–2016) were reviewed. We also manually searched reference lists of pertinent reviews and trials.ResultsA total of 6 pivotal Phase III randomized controlled trials known as the EDITION series were reviewed. All of these trials (n=3,500) were head-to-head comparisons evaluating the efficacy and tolerability of Gla-300 vs Gla-100 in a diverse population with T1DM and T2DM. These trials were of 6 months duration with a 6-month safety extension phase.ConclusionGla-300 was as effective as Gla-100 for improving glycemic control over 6 months in all studies, with a lower risk of nocturnal hypoglycemia significant only in insulin-experienced patients with T2DM. Overall, patients on Gla-300 required 10%–18% more basal insulin, but with less weight gain compared with Gla-100.

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Section: Resultsmentioning

confidence: 99%

rDNA insulin glargine U300 – a critical appraisal

Wang¹,

Zassman²,

Goldberg³

2016

DMSO

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“…In so doing, the investigators found clinically relevant and significant reductions in A1C and shed light on the extent of the increased efficacy of U-500 compared to U-100 regular insulin (11). …”

Section: Regular Insulin U-500mentioning

confidence: 97%

An Overview of Concentrated Insulin Products

Painter

Sisson

2016

Diabetes Spectrum

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IN BRIEF This article provides a summary of the use of available concentrated insulins in the outpatient treatment of patients with diabetes. Concentrated insulins work through the same mechanisms as other insulin products. They vary from each other in concentrations and pharmacokinetic/pharmacodynamics profiles but are each similar to their U-100 concentration counterparts. Patient education is important to minimize errors and the risk of hypoglycemia when using these insulin formulations.

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“…Prior to the U-500R titration-to-target trial, 1 clinicians had only their own clinical experience and largely retrospective, nonrandomized case reports/series, 25-29 real-world evidence studies, 30-32 and clinical reviews 3-5,33-37 to inform U-500R use. Treatment approaches varied among clinicians and experts, with some initiating U-500R with 1-to-1 total daily dose (TDD) transition (U-100 insulins to U-500R) evenly split over multiple daily doses (BID, TID, or 4-times-daily [QID]).…”

Section: Prior U-500r Dosing Recommendationsmentioning

confidence: 99%

“…1 The study followed a very structured initiation and titration protocol that called for a reduction in the initial U-500R dose by 20% of the U-100 insulin TDD for patients with an A1C ≤8% (≤64 mmol/mol) or mean plasma glucose <183 mg/dl (<10.16 mmol/l) (estimated average glucose for an A1C of 8% [64 mmol/mol] 38 ) within the 7 days before randomization. For patients with an A1C >8% (>64 mmol/mol) or mean plasma glucose ≥183 mg/dl (≥10.16 mmol/l), the U-500R starting dose was 100% of the U-100 insulin TDD.…”

Section: The U-500r Titration-to-target Rct: Summary Of Design and Rementioning

confidence: 99%

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Translating U-500R Randomized Clinical Trial Evidence to the Practice Setting: A Diabetes Educator/Expert Prescriber Team Approach

et al. 2017

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PurposeThe purpose of this article is to provide recommendations to the diabetes educator/expert prescriber team for the use of human regular U-500 insulin (U-500R) in patients with severely insulin-resistant type 2 diabetes, including its initiation and titration, by utilizing dosing charts and teaching materials translated from a recent U-500R clinical trial.ConclusionsClinically relevant recommendations and teaching materials for the optimal use and management of U-500R in clinical practice are provided based on the efficacy and safety results of and lessons learned from the U-500R clinical trial by Hood et al, current standards of practice, and the authors’ clinical expertise. This trial was the first robustly powered, randomized, titration-to-target trial to compare twice-daily and three-times-daily U-500R dosing regimens. Modifications were made to the initiation and titration dosing algorithms used in this trial to simplify dosing strategies for the clinical setting and align with current glycemic targets recommended by the American Diabetes Association. Leveraging the expertise, resources, and patient interactions of the diabetes educator who can provide diabetes self-management education and support in collaboration with the multidisciplinary diabetes team is strongly recommended to ensure patients treated with U-500R receive the timely and comprehensive care required to safely and effectively use this highly concentrated insulin.

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Two Treatment Approaches for Human Regular U-500 Insulin in Patients With Type 2 Diabetes not Achieving Adequate Glycemic Control on High-Dose U-100 Insulin Therapy With or Without Oral Agents: A Randomized, Titration-To-Target Clinical Trial

Cited by 54 publications

References 37 publications

rDNA insulin glargine U300 – a critical appraisal

rDNA insulin glargine U300 – a critical appraisal

An Overview of Concentrated Insulin Products

Translating U-500R Randomized Clinical Trial Evidence to the Practice Setting: A Diabetes Educator/Expert Prescriber Team Approach

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Two Treatment Approaches for Human Regular U-500 Insulin in Patients With Type 2 Diabetes not Achieving Adequate Glycemic Control on High-Dose U-100 Insulin Therapy With or Without Oral Agents: A Randomized, Titration-To-Target Clinical Trial

Cited by 54 publications

References 37 publications

rDNA insulin glargine U300 &ndash; a critical appraisal

rDNA insulin glargine U300 &ndash; a critical appraisal

An Overview of Concentrated Insulin Products

Translating U-500R Randomized Clinical Trial Evidence to the Practice Setting: A Diabetes Educator/Expert Prescriber Team Approach

Contact Info

Product

Resources

About

rDNA insulin glargine U300 – a critical appraisal

rDNA insulin glargine U300 – a critical appraisal