Insulin icodec: evolution or revolution in diabetes therapy?

Abstract

The isolation of insulin in 1922 was hailed as a miracle of medical science, life-saving for thousands and health-preserving for many more. 1 Bliss M The discovery of insulin. 6th edn. University of Chicago Press, Chicago, IL1984 Google Scholar Efforts to develop longer-acting formulations, to allow for more sustained glycaemic control and improve treatment satisfaction, started in the 1930s with initially the development of protamine (NPH) and zinc (lente) insulins. 2 Vecchio I Tornali C Bragazzi NL Martini M The discovery of insulin: an important milestone in the history of medicine. Front Endocrinol (Lausanne). 2018; 9: 613 Crossref PubMed Scopus (103) Google Scholar Subsequent decades saw the sequencing of the insulin molecule and a better understanding of its structure and action. 2 Vecchio I Tornali C Bragazzi NL Martini M The discovery of insulin: an important milestone in the history of medicine. Front Endocrinol (Lausanne). 2018; 9: 613 Crossref PubMed Scopus (103) Google Scholar Further research led to the development of human and analogue insulins. These incremental advances allowed greater flexibility in insulin administration and the potential to tailor insulin regimens that more closely mimic normal physiology. Despite these developments, however, achieving sustained glycaemic control while avoiding hypoglycaemia and weight gain together with preserving quality of life and treatment satisfaction remains a considerable challenge. 3 Sorli C Heile MK Identifying and meeting the challenges of insulin therapy in type 2 diabetes. J Multidiscip Healthc. 2014; 7: 267-282 Crossref PubMed Scopus (55) Google Scholar The search for molecules with better pharmacodynamic profiles has therefore continued and has led to an expanding list of so-called designer insulins. One such formulation is insulin icodec, with a half-life of 196 h, suitable for once-weekly administration. 4 Nishimura E Pridal L Glendorf T et al. Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing. BMJ Open Diabetes Res Care. 2021; 9e002301 Crossref Scopus (20) Google Scholar Its ultra-long-acting profile relates to a combination of lower affinity for the human insulin receptor and strong, but reversible, binding to human serum albumin. Switching to once-weekly insulin icodec versus once-daily insulin degludec in individuals with basal insulin-treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat-to-target trialAmong adults with basal insulin-treated type 2 diabetes, treatment with once-weekly icodec versus once-daily degludec demonstrated non-inferiority and statistical superiority in HbA1c reduction after 26 weeks, associated with modest weight gain. Overall rates of hypoglycaemia were low, with numerically but not statistically significantly higher event rates of level 2 or level 3 hypoglycaemia with icodec versus degludec. Full-Text PDF