After a preliminary attempt by Ciba-Geigy in 1974, Eli Lilly (in cooperation with Genentech) was the first company to succeed in producing human insulin on a grand scale in 1981. The key to this succes was biosynthesis, a process where the genetic code for human insulin was inserted in E. coli bacteria, that would grow in big tanks and produce the insulin. Novo soon followed this example by inserting the human insulin gene into yeasts. While human insulin sounded like a better option than animal insulins, in clinical practice this 'novel' insulin was not materially better than the animal insulins. In fact, in blinded studies patients and doctors were generally unable to tell the difference. However, pushed by a strong marketing effort, human insulin all but replaced the animal insulins by 1990.
Human insulin may have had few advantages over animal insulins, but neither did it have any specific disadvantages except for its price (which initially was twice as high as the animal insulin). Some patients claimed that the new insulin adversely affected their response to hypoglycaemia, but this could not be confirmed in a clinical trial that addressed this issue.
Like the animal insulins before, human insulin was marketed in four principal forms: as regular insulin, as NPH insulin, as mixtures of regular and NPH, and as Zinc (lente or ultralente) insulin. But while the animal insulins reigned supremely from 1922 to 1990, the reign of human insulin was soon under siege from the insulin analogues. The insulin analogues would supposedly remedy some of the pharmacokinetic flaws of subcutaneously injected human insulin and this, it was argued, would translate into more convenient insulin therapy and better glycemic control. As it turned out, the analogues did have more suitable pharmacokinetic profiles but in clinical practice the evidence has shown limited benefits other than some reduction in hypoglycaemic events. Nonetheless, in most industrialized countries the role of human insulin is dwindling.