Neutral Protamine Hagedorn (NPH) insulin, also known as isophane insulin, is an intermediate-acting insulin given to help control blood sugar levels in people with diabetes. The words refer to neutral pH (pH = 7), protamine a protein, and Hans Christian Hagedorn, the insulin researcher who invented this formulation. It is designed to improve the delivery of insulin, and is one of the earliest examples of engineered drug delivery.[3]
It is used by injection under the skin once to twice a day.[1] Onset of effects is typically in 90 minutes and they last for 24 hours.[3] Versions are available that come premixed with a short-acting insulin, such as regular insulin.[2]
Protamine insulin was first created in 1936 and NPH insulin in 1946.[1] It is on the World Health Organization's List of Essential Medicines.[4] NPH is an abbreviation for "neutral protamine Hagedorn".[1] In 2020, insulin isophane was the 221st most commonly prescribed medication in the United States, with more than 2million prescriptions.[5][6] In 2020, the combination of human insulin with insulin isophane was the 246th most commonly prescribed medication in the United States, with more than 1million prescriptions.[7][8]
Medical uses
NPH insulin is cloudy and has an onset of 1–3 hours. Its peak is 6–8 hours and its duration is up to 24 hours.[9]
It has an intermediate duration of action, meaning longer than that of regular and rapid-acting insulin, and shorter than long acting insulins (ultralente, glargine or detemir). A recent Cochrane systematic review[10] compared the effects of NPH insulin to other insulin analogues (insulin detemir, insulin glargine, insulin degludec) in both children and adults with Type 1 diabetes. Insulin detemir appeared provide a lower risk of severe hyperglycemia compared to NPH insulin, however this finding was inconsistent across included studies.[10] In the same review no other clinically significant differences were found between different insulin analogues in either adults nor children.[10]
In 1936, Hagedorn and B. Norman Jensen discovered that the effects of injected insulin could be prolonged by the addition of protamine obtained from the "milt" or semen of river trout. The insulin would be added to the protamine, but the solution would have to be brought to pH 7 for injection. University of Toronto, Canada later licensed protamine zinc insulin (PZI),[11] to several manufacturers. This mixture only needs to be shaken before injection. The effects of PZI lasted for 24–36 h.
In 1946, Nordisk was able to form crystals of protamine and insulin and marketed it in 1950, as neutral protamine Hagedorn (NPH) insulin. NPH insulin has the advantage that it can be mixed with an insulin that has a faster onset to complement its longer lasting action.[medical citation needed]
Eventually all animal insulins made by Novo Nordisk were replaced by synthetic, recombinant "human" insulin.[medical citation needed] Synthetic "human" insulin is also complexed with protamine to form NPH.[medical citation needed]
^ abcdBritish national formulary: BNF 69 (69 ed.). British Medical Association. 2015. pp. 464–472. ISBN9780857111562.
^ abcdefg"Insulin Human". The American Society of Health-System Pharmacists. Archived from the original on 22 October 2016. Retrieved 8 January 2017.
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^"The History of Insulin"(PDF). Karger.com/. Basel, Switzerland: Karger Publishers. Archived from the original(PDF) on March 4, 2016. Retrieved June 10, 2015.
