Synthetic long-acting insulin analogs for the management of type 1 diabetes: an update

Type 1 diabetes is characterized by insulin deficiency and requires near-physiological insulin replacement. In most patients, this is accomplished by basal bolus therapy consisting of a long-acting basal insulin administered once or twice daily and short-acting insulin with main meals. Several long-acting insulin analogs have been developed to optimize basal insulin therapy.

This paper reviews the design of - and data from - randomized controlled trials (RCTs) to assess glucose lowering efficacy and safety of long-acting insulin analogs for the treatment of type 1 diabetes.

Due to the non-inferiority treat-to-target design of insulin, RCTs treatment differences primarily appear as differences in hypoglycemia risk. Data suggest that the first generation long-acting insulin analogs insulin glargine U100 and insulin detemir have a similar glucose lowering efficacy compared to NPH insulin but a lower risk of hypoglycemia, particularly during nighttime. The newer analogs insulin glargine U300 and insulin degludec provide non-inferior efficacy, although insulin glargine U300 is less potent unit-to-unit. Insulin degludec reduces hypoglycemia risk compared to insulin glargine U100. Future studies should explore the potential for further improvement of treatment results in type 1 diabetes by a structured approach to personalization of basal insulin therapy.