Abstract

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 that lasts over 24h and provides an increased window of administration of 6h 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.

Highlights

  • Basal insulin therapy is currently recommended as an option following metformin when glycaemic targets are not reached in patients with type 2 diabetes (T2DM) and in combination with dual oral or other injectable glucose-lowering therapy or as part of a basal bolus regimen.[4]

  • Basal insulin is recommended in preference to pre-mixed or prandial insulins as glycaemic efficacy is not limited by excessive hypoglycaemia or weight gain as demonstrated in the 4T study.[5]

  • Another real-world study of 42,001 US patients switching from first generation basal insulins to either insulin glargine U300 or degludec, predictive modelling demonstrated no difference in rates of severe hypoglycaemia between the two newer insulins, providing further reassurance that either one is an appropriate choice in terms of hypoglycaemia data.[39]

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Summary

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

Background and Rationale for Development of Concentrated Insulin
Glycaemic Efficacy
Weight
Cardiovascular Safety
Hypoglycaemia
Real World Studies
Patient Adherence to Treatment
Duration of Action
Timing of Administration and Switching from First Generation Basal Insulins
Patient Groups Most Likely to Benefit
Potential Dispensing and Administration Errors
Outlook for Future Treatment Options
Conclusion
Findings
Participants
Full Text
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