Insulin (medication)/ja: Difference between revisions

In the United States the unit price of insulin has increased steadily from 1991 to 2019. It rose threefold from 2002 to 2013. Costs can be as high as US$900 per month. Concerns were raised in 2016 of pharmaceutical companies working together to increase prices. In January 2019, lawmakers from the [[United States House of Representatives]] sent letters to insulin manufacturers [[Eli Lilly and Co.]], [[Sanofi]] and [[Novo Nordisk]] asking for explanations for their rapidly raising insulin prices. The annual cost of insulin for people with type 1 diabetes in the U.S. almost doubled from $2,900 to $5,700 over the period from 2012 to 2016.

Insulin, and all other medications, are supplied free of charge to people who use it to manage their diabetes by the [[National Health Service]]s of the countries of the United Kingdom.

<div lang="en" dir="ltr" class="mw-content-ltr">

=== Regulatory status: United States ===

In March 2020, the FDA changed the regulatory pathway for approval of new insulin products. Insulin is regulated as a biologic rather than as a drug. The changed status gives the FDA more flexibility for approval and labeling. In July 2021, the FDA approved [[insulin glargine-yfgn]] (Semglee), a biosimilar product that contains the long acting analog insulin glargine. Insulin glargine-yfgn is interchangeable and less expensive than the reference product, [[insulin glargine]] (Lantus), which had been approved in 2000. The FDA requires that new insulin products are not inferior to existing insulin products with respect to reduction in hemoglobin A1c.

<div lang="en" dir="ltr" class="mw-content-ltr">

== Research ==

{{See also|Artificial pancreas}}

<div lang="en" dir="ltr" class="mw-content-ltr">

=== Inhalation ===

{{Main|Inhalable insulin}}

In 2006 the U.S. [[Food and Drug Administration]] (FDA) approved the use of [[Exubera]], the first inhalable insulin. It was withdrawn from the market by its maker as of third quarter 2007, due to lack of acceptance.

Inhaled insulin claimed to have similar efficacy to injected insulin, both in terms of controlling glucose levels and blood half-life. Currently, inhaled insulin is short acting and is typically taken before meals; an injection of long-acting insulin at night is often still required. When people were switched from injected to inhaled insulin, no significant difference was observed in Hb_A1c levels over three months. Accurate dosing was a particular problem, although people showed no significant weight gain or pulmonary function decline over the length of the trial, when compared to the baseline.

Following its commercial launch in 2005 in the United Kingdom, it was not (as of July 2006) recommended by [[National Institute for Health and Clinical Excellence]] for routine use, except in cases where there is "proven injection phobia diagnosed by a psychiatrist or psychologist".

In January 2008, the world's largest insulin manufacturer, [[Novo Nordisk]], also announced that the company was discontinuing all further development of the company's own version of inhalable insulin, known as the AERx iDMS inhaled insulin system. Similarly, [[Eli Lilly and Company]] ended its efforts to develop its inhaled Air Insulin in March 2008. [[Inhalable insulin|Afrezza]], developed by [[MannKind Corporation|Mannkind]], was authorized by the FDA in June 2014 for use in adults with Type I and Type II diabetes, with a label restriction limiting its use only to those who also have asthma, active lung cancer, or chronic obstructive pulmonary disease. Rapid-acting inhaled insulin is a component of the drug-device combination solution that is used at the start of every meal. It employs technosphere technology, which appears to have a more practical delivery method and more dosing flexibility, and a new inhaled insulin formulation (2.5 m). A thumb-sized inhaler with improved dosage flexibility is used to deliver inhalable insulin. It includes powder-dissolved recombinant human insulin (fumaryl diketopiperazine). Technosphere insulin is quickly absorbed by the lung surface after inhalation. Within 12 hours of inhalation, both substances—insulin, and powder (fumaryl diketopiperazine)—are virtually eliminated from healthy people's lungs. In comparison to [[Inhalable insulin|Exubera]] (8–9%), just 0.3% of inhaled insulin was still present in the lungs after 12 hours. However, since serum antibody levels have been reported to increase without substantial clinical changes, acute bronchospasm in asthmatic and COPD patients along with a significant reduction in Diffusing Lung Capacity for Carbon Monoxide, in comparison to subcutaneous insulin, have been reported with its usage, Afrezza was given FDA approval with a warning (Risk Evaluation and Mitigation Strategy).

<div lang="en" dir="ltr" class="mw-content-ltr">

=== Transdermal ===

There are several methods for transdermal delivery of insulin. [[Pulsatile insulin]] uses microjets to pulse insulin into the person, mimicking the physiological secretions of insulin by the pancreas. [[Jet injector|Jet injection]] had different insulin delivery peaks and durations as compared to needle injection. Some diabetics may prefer jet injectors to hypodermic injection. Both electricity using [[iontophoresis]] and ultrasound have been found to make the skin temporarily porous. The insulin administration aspect remains experimental, but the blood glucose test aspect of "wrist appliances" is commercially available Researchers have produced a watch-like device that tests for blood glucose levels through the skin and administers corrective doses of insulin through [[sebaceous gland|pores]] in the skin. A similar device, but relying on skin-penetrating "microneedles", was in the animal testing stage in 2015.  In the last couple of years, the use of chemical enhancers, electrical devices, and microneedle devices has shown tremendous promise for improving the penetration of insulin compared to passive transport via the skin . Transdermal insulin delivery shows a more patient-friendly and minimally invasive approach to daily diabetes care than the conventional hypodermic injection however, additional research is necessary to address issues such as long-term use, delivery efficiency, and reliability, as well as side effects involving inflammation and irritation.

<div lang="en" dir="ltr" class="mw-content-ltr">

=== Intranasal ===

<div lang="en" dir="ltr" class="mw-content-ltr">

=== By mouth ===

The basic appeal of hypoglycemic agents by mouth is that most people would prefer a pill or an oral liquid to an injection. However, insulin is a [[peptide hormone]], which is [[digestion|digested]] in the [[stomach]] and [[Gut (zoology)|gut]] and in order to be effective at controlling blood sugar, cannot be taken orally in its current form.

</div>

The potential market for an oral form of insulin is assumed to be enormous, thus many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the [[portal vein]] to have a measurable effect on blood sugar.

A number of [[prodrug|derivatization]] and [[pharmaceutical formulation|formulation]] strategies are currently being pursued to in an attempt to develop an orally available insulin. Many of these approaches employ [[nanoparticle]] delivery systems and several are being tested in [[clinical trial]]s.