had used
1923 Farbwerke Hoechst, one of the forerunners of todays Sanofi Aventis, produces commercial quantities of bovine insulin in Germany
1923 Hans Christian Hagedorn founds the Nordisk Insulinlaboratorium in Denmark – forerunner of todays Novo Nordisk
1923 Constance Collier returns to health after being successfully treated with insulin in Strasbourg
1926 Nordisk receives a Danish charter to produce insulin as a non-profit
1936 Canadians David M. Scott and Albert M. Fisher formulate a zinc insulin mixture at Connaught Laboratories in Toronto and license it to Novo
1936 Hagedorn discovers that adding protamine to insulin prolongs the duration of action of insulin
1946 Nordisk formulates Isophane porcine insulin aka Neutral Protamine Hagedorn or NPH insulin
1946 Nordisk crystallizes a protamine and insulin mixture
1950 Nordisk markets NPH insulin
1953 Novo formulates Lente porcine and bovine insulins by adding zinc for longer lasting insulin
1955 Frederick Sanger determines the amino acid sequence of insulin
1965 Synthesized by total synthesis by Wang Yinglai, Chen-Lu Tsou, et al. 1969 Dorothy Crowfoot Hodgkin solves the crystal structure of insulin by X-ray crystallography
1973 Purified monocomponent (MC) insulin is introduced
1973 The U.S. officially "standardized" insulin sold for human use in the U.S. to U-100 (100 units per milliliter). Prior to that, insulin was sold in different strengths, including U-80 (80 units per milliliter) and U-40 formulations (40 units per milliliter), so the effort to "standardize" the potency aimed to reduce dosage errors and ease doctors job of prescribing insulin for people. Other countries also followed suit.
The advantage of NPH is its low cost, the fact that you can mix it with short-acting forms of insulin, thereby minimizing the number of injections that must be administered, and that the activity of NPH will peak 4–6 hours after administration, allowing a bedtime dose to balance the tendency of glucose to rise with the dawn, along with a smaller morning dose to balance the lower afternoon basal need and possibly an afternoon dose to cover evening need. A disadvantage of bedtime NPH is that if not taken late enough (near midnight) to place its peak shortly before dawn, it has the potential of causing hypoglycemia. One theoretical advantage of glargine and detemir is that they only need to be administered once a day, although in practice many people find that neither lasts a full 24 hours. They can be administered at any time during the day as well, provided that they are given at the same time every day. Another advantage of long-acting insulins is that the basal component of an insulin regimen (providing a minimum level of insulin throughout the day) can be decoupled from the prandial or bolus component (providing mealtime coverage via ultra-short-acting insulins), while regimens using NPH and regular insulin have the disadvantage that any dose adjustment affects both basal and prandial coverage. Glargine and detemir are significantly more expensive than NPH, lente and ultralente, and they cannot be mixed with other forms of insulin.A short-acting insulin is used to simulate the endogenous insulin surge produced in anticipation of eating.