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  • Review Article
  • Published:

Insulin analogues in type 1 diabetes mellitus: getting better all the time

Key Points

  • Established rapid-acting and long-acting insulin analogues have enabled more patients with type 1 diabetes mellitus to reach better glucose targets, with lower hypoglycaemia rates and a better quality of life than was possible with short-acting and long-acting human insulin

  • In patients who are prone to severe hypoglycaemia, using a full analogue regimen is rapidly cost saving and should therefore be the standard of care in all patients with type 1 diabetes mellitus

  • The new long-acting insulin analogues insulin glargine U300 and insulin degludec have shown increased stability, which translates to a reduced risk of nocturnal hypoglycaemia and increased flexibility in timing of administration

  • Faster and shorter acting insulin analogues are needed for use in insulin pumps and future 'artificial pancreas' systems; fast-acting insulin aspart, a new formulation of aspart, is well advanced in clinical development

Abstract

The treatment of type 1 diabetes mellitus consists of external replacement of the functions of β cells in an attempt to achieve blood levels of glucose as close to the normal range as possible. This approach means that glucose sensing needs to be replaced and levels of insulin need to mimic physiological insulin-action profiles, including basal coverage and changes around meals. Training and educating patients are crucial for the achievement of good glycaemic control, but having insulin preparations with action profiles that provide stable basal insulin coverage and appropriate mealtime insulin peaks helps people with type 1 diabetes mellitus to live active lives without sacrificing tight glycaemic control. Insulin analogues enable patients to achieve this goal, as some have fast action profiles, and some have very slow action profiles, which gives people with type 1 diabetes mellitus the tools to achieve dynamic insulin-action profiles that enable tight glycaemic control with a risk of hypoglycaemia that is lower than that with human short-acting and long-acting insulins. This Review discusses the established and novel insulin analogues that are used to treat patients with type 1 diabetes mellitus and provides insights into the future development of insulin analogues.

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Figure 1: Different determinants of absorption and duration of action of human and analogue insulins.
Figure 2: Pharmacokinetic action profiles of rapid-acting insulins.
Figure 3: Pharmacodynamic action profiles of long-acting insulins.
Figure 4: Amino acid structure of short-acting and long-acting insulins.

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C.M. and K.B. researched data for the article, contributed to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission. P.G. contributed to discussion of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Chantal Mathieu.

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C.M. serves or has served on the advisory panel for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Intrexon, Janssen Pharmaceuticals, Hanmi Pharmaceuticals, Mannkind, Medtronic, Merck Sharp and Dohme Ltd., Novartis, Novo Nordisk, Pfizer, Sanofi, Roche Diagnostics and UCB. KU Leuven has received research support for C.M. from Abbott, Eli Lilly and Company, Intrexon, Merck Sharp and Dohme Ltd., Novartis, Novo Nordisk, Roche Diagnostics and Sanofi. C.M. serves or has served on the speakers bureau for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharp and Dohme, Novartis, Novo Nordisk and Sanofi. P.G. has served on the advisory panel for AstraZeneca, Lilly, Merck Sharp and Dohme Ltd., Novo Nordisk and Sanofi. P.G. has served on the speakers bureau for AstraZeneca, Bristol-Meyers Squibb, Boehringer Ingelheim, Janssen Pharmaceuticals, Lilly, Novartis, Novo Nordisk and Sanofi. K.B. has served on the advisory panel for AstraZeneca, Merck Sharp and Dohme Ltd. and Novo Nordisk. K.B. has served on the speakers bureau for AstraZeneca, Bristol-Meyers Squibb, Boehringer Ingelheim, Janssen Pharmaceuticals, Lilly, Novartis and Novo Nordisk. KU Leuven has received research grants for K.B. from AstraZeneca, Janssen Pharmaceuticals, Merck Sharp and Dohme Ltd., Novartis, Novo Nordisk and Sanofi.

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Mathieu, C., Gillard, P. & Benhalima, K. Insulin analogues in type 1 diabetes mellitus: getting better all the time. Nat Rev Endocrinol 13, 385–399 (2017). https://doi.org/10.1038/nrendo.2017.39

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