Insulin analogs in the treatment of type II diabetes and future perspectives

The discovery of insulin by Banting and Best marked 100 years in 2021, and it was a life-saving treatment modality for type II diabetes mellitus (T2DM). Insulin is a natural hormone that has been used extensively in T2DM patients since its discovery. Currently, insulin analogs are also available in different formulations for T2DM management, overcoming the limitations of human insulin with better safety and side effect profiles. The insulin analogs like the rapid-acting analogs (Aspart, lispro, glulisine), the long-acting basal analogs (Glargine, detemir), the ultra-long acting (Insulin degludec), and the premixed insulin analog formulations (75% Neutral protamine lispro, 25% lispro; 50% neutral protamine lispro, 50% lispro; 70% protamine aspart, 30% aspart) have been prepared through genetic engineering while preserving the basic insulin profile. A large number of studies have demonstrated their clinical effects on glycated hemoglobin test (HbA1c) in achieving glycemic control and thereby lowering the microvascular and macrovascular complications of T2DM with less traditional side effects of regular human insulin, mainly the risk of hypoglycemia, postprandial glycemic excursions, and weight gain. This review explores the currently available insulin analogs, their clinical implications, pharmacokinetics (PK), pharmacodynamics (PD), safety profile, and cost-effectiveness. We also discuss the future developments in the management of T2DM, especially the scientific advancements surrounding the novel insulin formulations, including the biosimilar insulin, and the innovative insulin delivery methods, such as oral and inhaled insulin.