New Insulins and New Aspects in Insulin Delivery

Woo, Vincent

doi:10.1016/j.jcjd.2015.04.006

Cited by 20 publications

(16 citation statements)

References 56 publications

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“…2 Reassuringly it has been shown experimentally that degludec has a low mitogenic-to-metabolic potency ratio. 12 The plasma half-life of degludec is 25 hours which is nearly double that of insulin glargine U100. 13…”

Section: Insulin Degludec (Tresiba®)mentioning

confidence: 99%

Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes

Chatterjee

Khunti

Davies

2019

Drugs

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The recent introduction of the second generation long-acting analogue insulins degludec and insulin glargine U300 have increased the choice of basal insulin therapy for patients with type 2 diabetes. The pharmacokinetic and pharmacodynamic properties of these insulins result in a flatter profile which lasts over 24 hours and provides an increased window of administration of six hours once daily. Large scale multicentre randomised clinical trial programmes (BEGIN for degludec U100 and U200 and EDITION for glargine U300) evaluating these insulin therapies against glargine U100 have demonstrated that they are either non-inferior or superior for glycaemic efficacy and safety but less likely to result in severe or nocturnal hypoglycaemia than glargine U100. The disposable pen devices for these insulins have been designed with patient satisfaction and convenience in mind. No concerns have arisen with adverse events with insulin analogues or cardiovascular safety from the ORIGIN and DEVOTE trials. As they demonstrate equivalent glycaemic efficacy to other basal insulins, they should be considered more in selected patient groups including those with recurrent or increased risk of hypoglycaemia, especially severe or nocturnal episodes, in the elderly or those living alone, and in patients with multiple co-morbidities such as cardiovascular or renal disease. Key Points • Second generation basal insulin analogues have demonstrated equivalent glycaemic efficacy to earlier basal insulin therapies but may result in lower risk of hypoglycaemia. • Selected patient groups at increased risk of hypoglycaemia such as elderly, those living alone or with multiple co-morbidities including cardiovascular or renal disease may be considered for treatment with insulin degludec or glargine U300.

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Section: Insulin Degludec (Tresiba®)mentioning

confidence: 99%

Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes

Chatterjee

Khunti

Davies

2019

Drugs

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“…9,12 Clinically, these characteristics prevent basal insulin gaps and hypoglycemia. Glargine U-300 users experienced fewer hypoglycemic episodes (14% reduction overall and 31% reduction in nocturnal hypoglycemia) 13,14 and less weight gain. 9 Adults with T1DM using glargine U-300 had fewer glycemic fluctuations as measured with continuous glucose monitoring than those using glargine U-100.…”

Section: Insulin Glargine: Toujeo U-300mentioning

confidence: 96%

New Insulin Preparations: Potential Benefits and Risk Assessments

Brackney¹

2016

The Journal for Nurse Practitioners

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Concentrated insulins have been especially problematic high alert medications. On February 25, 2015 Federal Drug Administration (FDA) approval made available insulin glargine, Toujeo U-300 (300 units/ml) in a SoloSTAR pen. On May 27, 2015 the FDA approved insulin lispro, Humalog U-200 (200 units/ml) KwikPen. Increased incidence of insulin resistant type 2 diabetes has escalated the need for concentrated insulin. This paper discusses each insulin, appropriate patient selection, benefits of the new insulins for people with diabetes and providers, and suggestions for prevention of potential off-label use of insulin pens. Counseling and assessment are essential to avoid unintended harm.

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“…Although, there was a shift in sedimentation coefficient values of the peaks over the period of two weeks and temperature of incubation (Table 3), the number of peaks remained constant, with an exception at 37 • C on day 7 for PIC complex. Therefore, it was concluded that interactions among PIC component were stable and the complex did not disintegrate at lower temperature for the tested timeframe (day [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. It is possible that at 37 • C the complex either dissociated or microbial growth would have occurred.…”

Section: Sedimentation Velocitymentioning

confidence: 99%

“…This spacer is attached to ε-amino group of Lys at B29 with hexadecanoic acid. IDeg exists in di-hexameric form where the two-hexamer units are linked together by Zn 2+ [5,6]. These changes are made to increase the pharmacokinetic profile of insulin by forming large supra-molecular structure as well as binding with albumin in the blood stream.…”

Section: Introductionmentioning

confidence: 99%

Clinically Relevant Insulin Degludec and Its Interaction with Polysaccharides: A Biophysical Examination

et al. 2020

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Protein polysaccharide complexes have been widely studied for multiple industrial applications and are popular due to their biocompatibility. Insulin degludec, an analogue of human insulin, exists as di-hexamer in pharmaceutical formulations and has the potential to form long multi-hexamers in physiological environment, which dissociate into monomers to bind with receptors on the cell membrane. This study involved complexation of two negatively charged bio-polymers xanthan and alginate with clinically-relevant insulin degludec (PIC). The polymeric complexations and interactions were investigated using biophysical methods. Intrinsic viscosity [η] and particle size distribution (PSD) of PIC increased significantly with an increase in temperature, contrary to the individual components indicating possible interactions. [η] trend was X > XA > PIC > A > IDeg. PSD trend was X > A > IDeg > XA > PIC. Zeta (ζ)-potential (with general trend of IDeg < A < XA < X ≈ PIC) revealed stable interaction at lower temperature which gradually changed with an increase in temperature. Likewise, sedimentation velocity indicated stable complexation at lower temperature. With an increase in time and temperature, changes in the number of peaks and area under curve were observed for PIC. Conclusively, stable complexation occurred among the three polymers at 4 • C and 18 • C and the complex dissociated at 37 • C. Therefore, the complex has the potential to be used as a drug delivery vehicle.Polymers 2020, 12, 390 2 of 15 Alginates (A) are linear polymers of 1,4-linked β-D-mannuronic acid residues and 1,4-linked α-L-guluronic residues, containing homo-polymeric sequences [7]. Xanthan (X) is composed of D-glucosyl, D-mannosyl, and D-glucuronyl acid residues in a 2:2:1 molar ratio and variable proportions of O-acetyl and pyruvyl residues. Its main chain consists of β-D-glucose units linked at the 1 and 4 positions. Side-chains consist of a tri-saccharide composed of mannose (β-1,4) glucuronic acid and (β-1,2) mannose, attached to alternate glucose residues in the backbone by α-1,3 linkages [8,9].Xanthan gum and alginate complexes (XA) have been studied previously [10] and used for functional foods [11], tissue engineering [3,12,13] and drug delivery. As negatively charged polymers, xanthan [14][15][16][17] and alginate [18][19][20] have been used separately, and in combination with positively charged polymers such as chitosan, as potential vehicles for insulin delivery.Interactions among different types of protein-polysaccharide complexes (PPCs) have been previously investigated using a variety of methods [21,22]. The formation and dissociation of PPCs and their solubility depend on many factors such as surface charge, pH, temperature and ionic strength of the solvent [23]. These factors greatly influence non-covalent interactions such as electrostatic, H-bonding, hydrophobic, and steric interactions, as well as covalent interactions [24]. Conjugation of polysaccharides with therapeutic proteins is a well-established phenomenon [25]. In particul...

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New Insulins and New Aspects in Insulin Delivery

Cited by 20 publications

References 56 publications

Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes

Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes

New Insulin Preparations: Potential Benefits and Risk Assessments

Clinically Relevant Insulin Degludec and Its Interaction with Polysaccharides: A Biophysical Examination

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