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In the year 2000 the first once daily long-acting bioengineered insulin analogue (LAIA), insulin glargine ('glargine'), a true basal insulin (BI), became available for clinical use. This led to the decline in the 50-year-old era and prominence of the intermediate-acting insulins, neutral protamine Hagedorn (NPH) and lente, requiring twice daily administration to control the basal metabolism of people with type 1 diabetes (T1DM) and type 2 diabetes (T2DM). This milestone bridged the gap between regimens involving unmodified human insulins of the previous century to those referred to as using 'designer insulins', with the introduction 4 years previously of the meal-time analogue, insulin lispro. The rapid gain in popularity of glargine is explained by its clinical benefits (once-daily dosing, titration to achieve improved pre-breakfast plasma glucose, with a lower risk of nocturnal hypoglycaemia compared to NPH, and less frequent blood glucose monitoring). These benefits correlate with the pharmacokinetic/pharmacodynamic characteristics of insulin glargine being closer to physiological BI supply. In T2DM glargine changed the paradigm of insulin substitution by embedding the concept of 'treating-to-target', by starting BI 'early', with focus on near-normal fasting plasma glucose prior to the introduction of prandial insulin, and more recently in combination with GLP-1 receptor agonists. These practices/principles have continued with the introduction of additional innovative LAIAs for once-daily or indeed weekly use. Today glargine remains in widespread worldwide use in people with T1DM and T2DM, is often the initial BI used, while it serves as a reference against which other LAIAs are tested in clinical trials.