Clinical Challenges With Concentrated Insulins: Setting the Record Straight

Brusko, Cynthia; Taylor, April D.; Jackson, Jeffrey A.; Bunck, Mathijs C.

doi:10.2337/ds17-0008

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…This attribute facilitates the use of U-500R as insulin monotherapy, which was tested and shown to significantly improve HbA1c in patients with type 2 diabetes inadequately controlled on high doses of U-100R therapy (> 200 units/day) ( 89 ). While total insulin exposure (AUC insulin and G tot ) was not statistically different between U-500R and U-100R, supporting unit dose equivalency (equipotency) ( 84 , 90 , 91 ), they are not bioequivalent and have different time-action profiles ( Fig. 17 ).…”

Section: Concentrated Insulinsmentioning

confidence: 83%

The Evolution of Insulin and How it Informs Therapy and Treatment Choices

et al. 2020

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Insulin has been available for the treatment of diabetes for almost a century, and the variety of insulin choices today represents many years of discovery and innovation. Insulin has gone from poorly defined extracts of animal pancreata to pure and precisely controlled formulations that can be prescribed and administered with high accuracy and predictability of action. Modifications of the insulin formulation and of the insulin molecule itself have made it possible to approximate the natural endogenous insulin response. Insulin and insulin formulations had to be designed to produce either a constant low basal level of insulin or the spikes of insulin released in response to meals. We discuss how the biochemical properties of endogenous insulin were exploited to either shorten or extend the time-action profiles of injectable insulins by varying the pharmacokinetics (time for appearance of insulin in the blood after injection) and pharmacodynamics (time-dependent changes in blood sugar after injection). This has resulted in rapid-acting, short-acting, intermediate-acting, and long-acting insulins, as well as mixtures and concentrated formulations. An understanding of how various insulins and formulations were designed to solve the challenges of insulin replacement will assist clinicians in meeting the needs of their individual patients.

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Section: Concentrated Insulinsmentioning

confidence: 83%

The Evolution of Insulin and How it Informs Therapy and Treatment Choices

et al. 2020

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“…Higher concentrations of insulin with or without modified pharmacokinetic (PK) and pharmacodynamics (PD) profiles have recently entered the market that fulfill different patient needs like the problems of injecting higher insulin dosages/ volumes such as, unpredictable absorption, leakage, and increased pain and discomfort 6,7 . Concentrated basal insulin analogs are currently available at 200 U/mL and 300 U/mL, whereas mealtime insulin (MTI) analog is available at 200 U/mL.…”

Section: Introductionmentioning

confidence: 99%

Patient characteristics of insulin lispro 200 units/mL users in real world setting in Germany

Schloot

Pérez-Nieves

Sapin³

et al. 2020

Current Medical Research and Opinion

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Objective: Insulin lispro 200 U/mL (IL200) is a treatment choice for people with diabetes who have daily mealtime insulin (MTI) requirements of >20 U/day. We report clinical characteristics of real world IL200 users in Germany to understand clinical settings and the type of patients who would benefit from IL200 treatment. Methods: This retrospective database analysis used the patient-level data from "IMS Disease Analyzer" in Germany from February 2015 to June 2016. Clinical and demographic information were collected and analyzed for IL200 users alongside that of those who were using more than 20 U a day of 100 U/ mL analog MTI. Results: Of the 17,261 patients using insulin, 811 were identified in IL200 group. The IL200 group had 60% men, mean ± SD age of 63.6 ± 11.9 years, and BMI of 36.2 ± 6.7 kg/m 2. Of these, 63.5% (n ¼ 515) were seen by diabetologists, while 36.5% (n ¼ 296) were seen by general practitioners (GPs). In the IL200 group, 77.7% used basal insulin concomitantly, >90% had !1 comorbidity, and 52% had !4 comorbidities; the most common being hypertension (75.2%), neuropathy (66.0%), and nephropathy (59.6%). Diabetologist-treated IL200 users were more likely to have multiple comorbidities as compared with those treated by GPs (15.0% vs. 12.9% for >5 comorbidities). Conclusions: IL200 is prescribed to people with diabetes who need more than 20 U/day of mealtime insulin and tend to be more obese, older, and with multiple comorbidities. Future research should explore how concentrated MTI can impact adherence and long-term glycemia.

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“…Given the fact that the other concentrated prandial insulin analogs do not primarily target severely insulin-resistant patients, but were developed to provide longer-lasting pens ( 29 ), availability of a U500 insulin with a rapid PK/PD profile is currently lacking. The superior insulin exposure and action of AT278 U500 within the first 30 and 60 min postdose suggest that AT278 U500 will enable dosing at meal or even after meal without compromising postprandial glucose control and will thus provide more flexibility with meals and daily schedule for people with high insulin needs.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of a Novel U500 Insulin Aspart Formulation: A Randomized, Double-Blind, Crossover Study in People With Type 1 Diabetes

et al. 2023

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OBJECTIVE To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 U500) compared with insulin aspart (IAsp U100). RESEARCH DESIGN AND METHODS This single-center, randomized, double-blind study was conducted in 38 men with type 1 diabetes (body weight ≤100 kg and total insulin dose <1.2 units/kg/day). Participants received a single dose of either AT278 U500 or IAsp U100 (0.3 units/kg s.c.) in a crossover design, followed by an 8-h euglycemic clamp in the absence of basal insulin. RESULTS With AT278 U500, onset of appearance in serum was 6 min earlier (P < 0.0001) and reached 50% of maximum concentration 23 min faster (P < 0.0001). Insulin exposure with AT278 U500 was 4.0-fold higher within the first 30 min (95% CI 3.29, 4.90), 1.5-fold higher within the first 60 min (95% CI 1.35, 1.76), and statistically superior up to 90 min postdose (P < 0.05). With AT278 U500, onset of action was 10 min earlier (P < 0.0001) and reached 50% of maximum glucose infusion rate 20 min faster (P < 0.0001). The glucose-lowering effect with AT278 U500 was 8.9-fold higher within the first 30 min (95% CI 5.96, 17.46), 2.4-fold higher within the first 60 min (95% CI 1.92, 3.22), and statistically superior up to 2 h postdose (P < 0.0001). Overall insulin exposure and glucose-lowering effect were comparable. No significant safety findings were observed. CONCLUSIONS AT278 U500 offers rapid-acting characteristics in a reduced dose volume, with accelerated absorption and onset of action compared with IAsp U100 in the studied population.

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Clinical Challenges With Concentrated Insulins: Setting the Record Straight

Cited by 3 publications

References 26 publications

The Evolution of Insulin and How it Informs Therapy and Treatment Choices

The Evolution of Insulin and How it Informs Therapy and Treatment Choices

Patient characteristics of insulin lispro 200 units/mL users in real world setting in Germany

Pharmacokinetics and Pharmacodynamics of a Novel U500 Insulin Aspart Formulation: A Randomized, Double-Blind, Crossover Study in People With Type 1 Diabetes

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