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  • Review Article
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One hundred years of insulin therapy

Nature Reviews Endocrinology volume 17, pages 715–725 (2021)Cite this article

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Abstract

At the time of its first clinical application 100 years ago, insulin was presented as the cure for people with diabetes mellitus. That transpired to be an overstatement, yet insulin has proven to be the lifesaver for people with type 1 diabetes mellitus and an essential therapy for many with type 2 diabetes mellitus or other forms of diabetes mellitus. Since its discovery, insulin (a molecule of only 51 amino acids) has been the subject of pharmaceutical research and development that has paved the way for other protein-based therapies. From purified animal-extracted insulin and human insulin produced by genetically modified organisms to a spectrum of insulin analogues, pharmaceutical laboratories have strived to tailor the preparations to the needs of patients. Nonetheless, overall glycaemic control often remains poor as exogenous insulin is still not able to mimic the physiological insulin profile. Circumventing subcutaneous administration and the design of analogues with profiles that mimic that of physiological insulin are ongoing areas of research. Novel concepts, such as once-weekly insulins or glucose-dependent and oral insulins, are on the horizon but their real-world effectiveness still needs to be proven. Until a true cure for type 1 diabetes mellitus is found and the therapeutic arsenal for other forms of diabetes mellitus is expanded, insulin will remain central in the treatment of many people living with diabetes mellitus.

Key points

  • Insulin has proven to be a lifesaver for people with type 1 diabetes mellitus and an essential therapy for many people with type 2 diabetes mellitus or other forms of diabetes mellitus.

  • Since its discovery, insulin has been the subject of extensive pharmaceutical research and development that has also paved the way for other protein-based therapies.

  • Initially, advancements were mainly focused on improving the quality of life by reducing the frequency of injections and reducing antigenicity.

  • Since the Diabetes Control and Complications Trial in 1993, the focus has shifted towards mimicking the physiological insulin profile.

  • The risk of hypoglycaemia remains a major burden of insulin therapy.

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Fig. 1: A timeline of the major scientific and pharmaceutical discoveries in the development of insulin with the approximate historical dates.
Fig. 2: Past, current and future challenges of insulin.

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Authors and Affiliations

  1. Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium

    Chantal Mathieu, Pieter-Jan Martens & Roman Vangoitsenhoven

  2. Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium

    Chantal Mathieu, Pieter-Jan Martens & Roman Vangoitsenhoven

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The authors contributed equally to all aspects of the article.

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Competing interests

C.M. serves or has served on the advisory panel for Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet and Zealand Pharma. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for C.M. from Medtronic, Novo Nordisk, Sanofi and ActoBio Therapeutics; C.M. serves or has served on the speakers’ bureau for Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, AstraZeneca and Novartis. Financial compensation for these activities has been received by KU Leuven. R.V. serves or has served on the speakers’ bureau for Novo Nordisk, Sanofi, Boehringer Ingelheim, AstraZeneca and Mundipharma. Financial compensation for these activities has been received by KU Leuven. P.-J. M. declares no competing interests.

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Mathieu, C., Martens, PJ. & Vangoitsenhoven, R. One hundred years of insulin therapy. Nat Rev Endocrinol 17, 715–725 (2021). https://doi.org/10.1038/s41574-021-00542-w

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