NPH insulin

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NPH insulin
Insulin&Syringe.JPG
A vial of NPH insulin with insulin syringe
Clinical data
Trade names Novolin N, Humulin N, Insulatard, others
Other namesNeutral protamine Hagedorn insulin, [1]
protamine zinc insulin (slightly different), [2]
isophane insulin, [2]
compound insulin zinc suspension (slightly different), [2]
intermediate-acting insulin
AHFS/Drugs.com Monograph
MedlinePlus a682611
Routes of
administration
Subcutaneous
ATC code
Legal status
Legal status
Pharmacokinetic data
Onset of action 90 minutes [3]
Duration of action 24 hours [3]
Identifiers
CAS Number
ChemSpider
  • none

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. [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]

Contents

The common side effect is low blood sugar. [3] Other side effects may include pain or skin changes at the sites of injection, low blood potassium, and allergic reactions. [3] Use during pregnancy is relatively safe for the fetus. [3] NPH insulin is made by mixing regular insulin and protamine in exact proportions with zinc and phenol such that a neutral-pH is maintained and crystals form. [1] There are human and pig insulin based versions. [1]

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 2 million 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 1 million 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]

History

Hans Christian Hagedorn (1888–1971) and August Krogh (1874–1949) obtained the rights for insulin from Frederick Banting and Charles Best in Toronto, Canada. In 1923 they formed Nordisk Insulin laboratorium, and in 1926 with August Kongsted he obtained a Danish royal charter as a non-profit foundation.

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 ]

Timeline

The timeline is as follows:[ citation needed ]

Society and culture

Names

NPH stands for neutral protamine Hagedorn, and the words refer to neutral pH (pH = 7), protamine (a protein), and Hans Christian Hagedorn (an insulin researcher).Brand names include Humulin N, Novolin N, Novolin NPH, Gensulin N, SciLin N, Insulatard, and NPH Iletin II.[ citation needed ]

See also

Related Research Articles

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<span class="mw-page-title-main">Insulin glargine</span> Long-acting insulin

Insulin glargine sold under the brand name Lantus among others is a long-acting modified form of medical insulin, used in the management of type I and type II diabetes. It is injected just under the skin. Effects generally begin an hour after use.

An insulin analog is any of several types of medical insulin that are altered forms of the hormone insulin, different from any occurring in nature, but still available to the human body for performing the same action as human insulin in terms of controlling blood glucose levels in diabetes. Through genetic engineering of the underlying DNA, the amino acid sequence of insulin can be changed to alter its ADME characteristics. Officially, the U.S. Food and Drug Administration (FDA) refers to these agents as insulin receptor ligands, although they are usually just referred to as insulin analogs or even just insulin.

<span class="mw-page-title-main">Exenatide</span> Medication

Exenatide, sold under the brand name Byetta and Bydureon among others, is a medication used to treat diabetes mellitus type 2. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after metformin and sulfonylureas. It is given by injection under the skin twice daily or once weekly.

Insulin detemir, sold under the brand name Levemir among others, is a long-acting modified form of medical insulin used to treat both type 1 and type 2 diabetes. It is used by injection under the skin. It is effective for up to 24 hours.

<span class="mw-page-title-main">Insulin aspart</span> Rapid-acting man-made insulin

Insulin aspart, sold under the brand name NovoLog, among others, is a modified type of medical insulin used to treat type 1 and type 2 diabetes. It is generally used by injection under the skin but may also be used by injection into a vein. Maximum effect occurs after about 1–3 hours and lasts for 3–5 hours. Generally a longer-acting insulin like insulin NPH is also needed.

<span class="mw-page-title-main">Insulin lispro</span> Rapid-acting insuline analog

Insulin lispro, sold under the brand name Humalog among others, is a modified type of medical insulin used to treat type 1 and type 2 diabetes. It is used by injection under the skin or within an insulin pump. Onset of effects typically occurs within 30 minutes and lasts about 5 hours. Often a longer-acting insulin like insulin NPH is also needed.

<span class="mw-page-title-main">Liraglutide</span> Anti-diabetic medication

Liraglutide, sold under the brand names Victoza and Saxenda among others, is an anti-diabetic medication used to treat type 2 diabetes, and chronic obesity. It is a second-line therapy for diabetes following first-line therapy with metformin. Its effects on long-term health outcomes like heart disease and life expectancy are unclear. It is given by injection under the skin.

<span class="mw-page-title-main">Regular insulin</span> Short-acting insulin formulation

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<span class="mw-page-title-main">Hans Christian Hagedorn</span>

Hans Christian Hagedorn was the creator of NPH insulin and the founder of Nordisk Insulinlaboratorium, which is known today as Novo Nordisk.

<span class="mw-page-title-main">Lente insulin</span> Historical formulation of insulin as medication

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<span class="mw-page-title-main">Insulin degludec</span> Ultralong-acting basal insulin analogue

Insulin degludec (INN/USAN) is an ultralong-acting basal insulin analogue that was developed by Novo Nordisk under the brand name Tresiba. It is administered via subcutaneous injection once daily to help control the blood sugar level of those with diabetes. It has a duration of action that lasts up to 42 hours, making it a once-daily basal insulin, that is one that provides a base insulin level, as opposed to the fast- and short-acting bolus insulins.

Ultralente insulin was a long-acting form of insulin. It has an onset of 4 to 6 hours, a peak of 14 to 24 hours, and a duration of 28 to 36 hours. Ultralente insulin, along with lente insulin, were discontinued in the US by manufacturers in the mid-2000s. One of the reasons for discontinuation was declining use in favor of NPH insulin and other newer insulin products. The FDA withdrew approval for ultralente insulin products by 2011.

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Thomas Rudolf Pieber is an Austrian clinical specialist in endocrinology and diabetes. He is Professor of Medicine, Head of the Division of Endocrinology and Metabolism and Chairman of the Department of Internal Medicine at the Medical University of Graz. He is also Director of the Institute of Biomedicine and Health Sciences at Joanneum Research.

References

  1. 1 2 3 4 5 6 Owens DR (1986). Human Insulin: Clinical Pharmacological Studies in Normal Man. Springer Science & Business Media. pp. 134–136. ISBN   9789400941618. Archived from the original on 2017-01-18.
  2. 1 2 3 4 British national formulary: BNF 69 (69 ed.). British Medical Association. 2015. pp. 464–472. ISBN   9780857111562.
  3. 1 2 3 4 5 6 7 "Insulin Human". The American Society of Health-System Pharmacists. Archived from the original on 22 October 2016. Retrieved 8 January 2017.
  4. 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.
  5. "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  6. "InsulinIsophane - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  7. "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  8. "Insulin Human; Insulin Isophane Human - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  9. "NPH insulin | DrugBank Online". go.drugbank.com. Retrieved 2022-09-09.
  10. 1 2 3 Hemmingsen B, Metzendorf MI, Richter B (March 2021). "(Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus". The Cochrane Database of Systematic Reviews. 3 (3): CD013498. doi:10.1002/14651858.cd013498.pub2. PMC   8094220 . PMID   33662147.
  11. "The History of Insulin" (PDF). Karger.com/. Basel, Switzerland: Karger Publishers. Archived from the original (PDF) on March 4, 2016. Retrieved June 10, 2015.