United States experience of insulin degludec alone or in combination for type 1 and type 2 diabetes

Insulin degludec has been the product of a sophisticated and systematic biochemical engineering program which began with the release of insulin detemir. The goal was to produce a long-lasting basal insulin with low individual variability. Certainly, this goal has been achieved. Degludec has a duration of action approaching twice that of glargine. Another advantage of degludec is in its lack of unpredictable copolymerization of added aspart. In several studies, degludec has shown lower rates of nocturnal hypoglycemia than glargine. Degludec can be administered flexibly with a very flat insulin concentration curve at any time of day. Initial US Food and Drug Administration concerns about a possible increase in cardiac events in degludec-treated patients have been allayed by the results of a study targeting individuals with high cardiac risk. Degludec is now marketed in the US competing with glargine. Despite the long duration of action of degludec, attempted administration three times weekly resulted in less effective lowering of glycated hemoglobin and an increased incidence of hypoglycemia compared to daily glargine. Conversely the coformulation of degludec and liraglutide has proven very successful in reducing glycated hemoglobin levels with less hypoglycemia and less weight gain than with degludec alone and with less gastrointestinal symptoms than with liraglutide alone. A large study comparing glargine insulin and degludec in patients with increased cardiac risk is now ongoing. This study may or may not prove superiority of one or the other insulin, but, with the coming of biosimilar glargine insulin, cost factors may be dominant in determining which basal insulin is to be used. Nonetheless, the coformulation with liraglutide will likely insure the future of degludec insulin in the treatment of type 2 diabetes.