Gla-100 Development: a Story of 'Serendipitous' Disruptive Innovation

Ever since the discovery of insulin a century ago, relentless attempts have been made to develop insulins that closely mimic the timeaction- profile of human physiologic insulin. The early basal insulins like neutral protamine Hagedorn (NPH), were intermediate-acting, with high risk of hypoglycemia. These primary limitations led to attempts at developing improved basal insulins with a longer duration of action. After several attempts at prolonging insulin action using phenol and structural modifications of the insulin hexamer, insulin glargine was developed in 1988. The superior and unique pharmacological properties, longer duration of action, and significantly lowered risk of hypoglycemia enabled insulin glargine to be distinguished from NPH as a better basal insulin, providing holistic glycemic control. The present review highlights the circumstances that led to the search of truly basal insulins, focusing on the journey of insulin glargine 100 U/mL (Gla-100).