Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin

Jonassen, Inge; Havelund, Svend; Høeg-Jensen, Thomas; Steensgaard, Dorte B.; Wahlund, Per-Olof; Ribel, Ulla

doi:10.1007/s11095-012-0739-z

Cited by 410 publications

(466 citation statements)

References 29 publications

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“…T 6 , T 3 R f 3 , and R 6 families of insulin hexamers have each been employed in pharmaceutical formulations (9,59). Their conformational equilibria may be shifted in favor of the more stable R family through the binding of small cyclic alcohols, such as phenol or meta-cresol or with lower affinity, as cyclohexanol (60).…”

Section: Discussionmentioning

confidence: 99%

Biophysical Optimization of a Therapeutic Protein by Nonstandard Mutagenesis

Pandyarajan

Phillips

Cox

et al. 2014

Journal of Biological Chemistry

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Background: Therapeutic engineering of insulin analogs is ordinarily limited by a trade-off between pharmacokinetics and stability. Results: Substitution of Tyr B26 in a rapid-acting insulin analog by 3-iodo-Tyr B26 enhances its biophysical and pharmaceutical properties. Conclusion: An unnatural amino acid substitution circumvents insulin pharmacokinetic/stability trade-off. Significance: Nonstandard mutagenesis can optimize the molecular properties of therapeutic proteins.

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Section: Discussionmentioning

confidence: 99%

Biophysical Optimization of a Therapeutic Protein by Nonstandard Mutagenesis

Pandyarajan

Phillips

Cox

et al. 2014

Journal of Biological Chemistry

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“…Accordingly, insulin degludec has been developed as a next‐generation, long‐acting, soluble insulin analog that provides a longer duration of activity10. In clinical pharmacological studies, insulin degludec exerted a long‐lasting action (>42 h)11, with a flat and stable insulin profile in the glucose‐lowering effect for individual patients12.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of insulin degludec in Japanese patients with type 1 and type 2 diabetes: 24‐week results from the observational study in routine clinical practice

Kobuke

Yoneda

Nakanishi

et al. 2015

J of Diabetes Invest

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Aims/IntroductionInsulin degludec, a new long‐acting insulin analog, showed its better glycemic control and reduced risk of hypoglycemia. This is the first prospective observational study that evaluated the efficacy and safety of insulin degludec in routine clinical practice.Materials and MethodsJapanese patients with type 1 or type 2 diabetes mellitus receiving basal–bolus insulin therapy were switched their basal insulin to degludec, and prospectively observed over a 24‐week course. The Diabetes Therapy‐Related Quality of Life questionnaire was administered before and 12 weeks after switching.ResultsThe participants were 80 diabetes patients = (type 1, 44; type 2, 36). In the type 1 group, there was no difference in glycated hemoglobin levels between the pre‐switching and 24‐week measurements (from 62 to 62 mmol/mol, P = 0.768), whereas the daily insulin dose (per kg of bodyweight) decreased significantly (basal, from 0.25 to 0.20 U/kg, P < 0.001; bolus, from 0.40 to 0.37 U/kg, P = 0.001). In the type 2 group, glycated hemoglobin levels decreased after switching (from 60 to 58 mmol/mol, P = 0.028). In the type 1 group, the frequency of hypoglycemia decreased significantly after switching, but not significantly in the type 2 group. Patient satisfaction with the control of hypoglycemia tended to improve in the type 1 group.ConclusionsCompared with existing long‐acting insulin, degludec can maintain glycemic control at a lower insulin dose and frequency of hypoglycemia in type 1 diabetes, while it can improve glycemic control at an equal insulin dose in type 2 diabetes.

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“…Following subcutaneous injection and thanks to phenol dispersion, IDeg the dihexamers self-associate to form a stable depot of multi-hexamer chains at the injection site. With the gradual diffusion of zinc, however, these chains are expected to gradually disassemble to release monomers from the terminal ends of multihexamers 11,12 (Figure 1). …”

Section: New-generation Basal Insulin Analoguementioning

confidence: 99%

Inpatient hyperglycemia management: the opportunities of a new basal insulin

Simioni¹

2016

Ital J Med

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The management of hospitalized diabetic patients for any cause is often difficult and affected not only by the comorbidities of the patient but also by the hospital setting. It is well known that at the admission the antidiabetic drugs should be discontinued on behalf of insulin therapy with insulin analogues, as a function of a basal-bolus insulin approach according to the phenotype of the patient, type of nutrition (enteral or parenteral rather than oral), or concomitant hyperglycemic therapy (e.g., steroid). The average stay of diabetic patients hospitalized for any cause is significantly correlated with both the number of hypoglycemia and hyperglycemia. Compared to patients treated with sliding scale patients using a custom algorithm show a significant reduction in the number of hypoglycemia and hyperglycemia episodes and in the length of stay. We analyze the clinical profile of a novel basal insulin, degludec, and explore the potential clinical benefit for diabetic inpatient. The continuation of insulin therapy at home in the immediate post-hospitalization (if necessary), also correlates with a reduction in the rate of re-hospitalization, which combined with close follow-up diabetes can result in a reduction of chronic complications.

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Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin

Cited by 410 publications

References 29 publications

Biophysical Optimization of a Therapeutic Protein by Nonstandard Mutagenesis

Biophysical Optimization of a Therapeutic Protein by Nonstandard Mutagenesis

Efficacy and safety of insulin degludec in Japanese patients with type 1 and type 2 diabetes: 24‐week results from the observational study in routine clinical practice

Inpatient hyperglycemia management: the opportunities of a new basal insulin

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