Ultra Rapid Lispro (URLi) Accelerates Insulin Lispro Absorption and Insulin Action vs Humalog® Consistently Across Study Populations: A Pooled Analysis of Pharmacokinetic and Glucodynamic Data

Leohr, Jennifer; Dellva, Mary Anne; Carter, Kallin; Labell, Elizabeth S.; Linnebjerg, Helle

doi:10.1007/s40262-021-01030-0

Cited by 20 publications

(14 citation statements)

References 25 publications

(40 reference statements)

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“…33 Similarly, URLi showed earlier insulin action while reducing late insulin action, resulting in a shorter duration of insulin action compared with Humalog across the study populations (healthy subjects and patients with T1DM and T2DM) and dose range reflected in the individual studies and in the pooled analysis. 37 Also, although all participants in the study were male, the data are expected to be representative of both male and female subjects because no difference in sex has been identified with URLi in previous studies. 35 Despite the euglycemic clamp being the gold standard for assessing insulin action, a limitation of this procedure is that it does not measure the glucose-lowering effects of the insulin after oral carbohydrate intake.…”

Section: Discussionmentioning

confidence: 97%

Evaluation of the Pharmacokinetic Profile of Ultra Rapid Lispro Administered Subcutaneously at Different Injection Sites

Leohr

Dellva

Labell

et al. 2022

Clinical Therapeutics

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Section: Discussionmentioning

confidence: 97%

Evaluation of the Pharmacokinetic Profile of Ultra Rapid Lispro Administered Subcutaneously at Different Injection Sites

Leohr

Dellva

Labell

et al. 2022

Clinical Therapeutics

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“…A pooled analysis of the PK and PD of URLi across different population groups has been published 30 . The analysis included four randomized, double‐blind, crossover, single‐dose studies (PwoD [n = 74], people with type 1 diabetes [n = 78] and type 2 diabetes [n = 38]) evaluating subcutaneous doses of URLi and Lispro during an 8‐ to 10‐hour euglycaemic clamp procedure.…”

Section: Pharmacokinetic and Pharmacodynamic Profile Of Urlimentioning

confidence: 99%

“…A pooled analysis of the PK and PD of URLi across different population groups has been published. 30 The analysis included four random- Following subcutaneous injection, URLi was absorbed more rapidly, showing reduced late exposure and a shorter duration of action compared with Lispro (Table 1). URLi showed 5-minute faster onset of appearance in serum, an $8-fold greater exposure in the first 15 minutes, and a 43% reduction in exposure beyond 3 hours compared with Lispro across all study populations and dose ranges (Table 1).…”

Section: Subcutaneous Injectionmentioning

confidence: 99%

What is the value of faster acting prandial insulin? Focus on ultra rapid lispro

Heise

Oliveira

Juneja

et al. 2022

Diabetes Obesity Metabolism

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Rapid‐acting insulins (RAIs) have been instrumental in the management of diabetes because of their improved postprandial glucose (PPG) control compared with regular human insulin. However, their absorption rate and time action following subcutaneous administration still falls short of the normal physiological response to meal consumption, increasing the risk of early postmeal hyperglycaemia and late postmeal hypoglycaemia. Increased demand for faster acting insulins, which can quickly control PPG excursions without increasing the risk of late hypoglycaemia, led to the development of ultra‐rapid–acting insulins, including ultra‐rapid lispro (URLi). URLi is a novel formulation of insulin lispro with accelerated absorption driven by two excipients: treprostinil, which increases local vasodilation, and citrate, which increases local vascular permeability. Clinical pharmacology studies consistently showed an earlier onset and shorter duration of action with URLi compared with Lispro. In a head‐to‐head study with Faster aspart, Aspart and Lispro, URLi was absorbed faster, provided earlier insulin action, and more closely matched physiological glucose response than the other insulins tested. URLi's unique pharmacokinetic properties increase its potential for improved PPG control beyond that achieved with RAIs. Indeed, in pivotal phase 3 trials, URLi was superior to Lispro for PPG control both at 1 and 2 hours after a meal in type 1 and type 2 diabetes with multiple daily injections, and in type 1 diabetes with continuous subcutaneous insulin infusion. This was achieved without increasing the risk of hypoglycaemia. In this review, we focus on the clinical and pharmacological evidence for URLi in the treatment of diabetes and discuss the potential benefits and considerations with URLi compared with RAIs.

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“…Lyumjev ® contains the vasodilating drug treprostinil, a stable prostacyclin analogue, and citrate in addition to insulin lispro ( The Norwegian Medicines Agency Medicine Database, Lyumjev, 2022 ). This combination leads to significantly faster SC absorption, elimination, and earlier onset of action of insulin lispro ( Leohr et al, 2021 ). Fiasp ® contains niacinamide and l -arginine together with insulin aspart.…”

Section: Factors Delaying Onset Of Insulin Action In Sc Artificial Pa...mentioning

confidence: 99%

Vasodilatory effects of glucagon: A possible new approach to enhanced subcutaneous insulin absorption in artificial pancreas devices

Teigen

Riaz

Åm

et al. 2022

Front. Bioeng. Biotechnol.

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Patients with diabetes mellitus type 1 depend on exogenous insulin to keep their blood glucose concentrations within the desired range. Subcutaneous bihormonal artificial pancreas devices that can measure glucose concentrations continuously and autonomously calculate and deliver insulin and glucagon infusions is a promising new treatment option for these patients. The slow absorption rate of insulin from subcutaneous tissue is perhaps the most important factor preventing the development of a fully automated artificial pancreas using subcutaneous insulin delivery. Subcutaneous insulin absorption is influenced by several factors, among which local subcutaneous blood flow is one of the most prominent. We have discovered that micro-doses of glucagon may cause a substantial increase in local subcutaneous blood flow. This paper discusses how the local vasodilative effects of micro-doses of glucagon might be utilised to improve the performance of subcutaneous bihormonal artificial pancreas devices. We map out the early stages of our hypothesis as a disruptive novel approach, where we propose to use glucagon as a vasodilator to accelerate the absorption of meal boluses of insulin, besides using it conventionally to treat hypoglycaemia.

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Ultra Rapid Lispro (URLi) Accelerates Insulin Lispro Absorption and Insulin Action vs Humalog® Consistently Across Study Populations: A Pooled Analysis of Pharmacokinetic and Glucodynamic Data

Cited by 20 publications

References 25 publications

Evaluation of the Pharmacokinetic Profile of Ultra Rapid Lispro Administered Subcutaneously at Different Injection Sites

Evaluation of the Pharmacokinetic Profile of Ultra Rapid Lispro Administered Subcutaneously at Different Injection Sites

What is the value of faster acting prandial insulin? Focus on ultra rapid lispro

Vasodilatory effects of glucagon: A possible new approach to enhanced subcutaneous insulin absorption in artificial pancreas devices

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