Human insulin is a hormone produced by the body that helps turn food into energy and controls blood sugar levels. People with diabetes cannot make enough insulin and those with type 1 diabetes have to inject insulin several times a day, typically before every meal. Insulin is an essential medicine for people with diabetes and current guidance states that before use it must be kept refrigerated to preserve its effectiveness.

There are two major forms of diabetes, type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). T1DM is the major cause of diabetes in childhood and adolescence, and injections of insulin are necessary for survival. In the tenth revision of its diabetes atlas, the International Diabetes Federation (IDF) estimated that the number of people with diabetes worldwide would increase from 573 million people in 2021 to 783 million people in 2045, representing a 46% increase (IDF 2021). 

T2DM accounts for approximately 90% of diabetes and is associated with insulin resistance: as a consequence of ineffective insulin action to transport glucose into cells, an increased insulin demand develops and over time inadequate insulin production occurs due to exhaustion of pancreatic ß?cells. T2DM being related to obesity and lack of exercise is initially treated with exercise/diet and oral glucose?lowering drugs, but insulin may be needed to further improve diabetes management and in case pancreatic ß?cells are not able to compensate for the increased insulin demand. The need for insulin to treat T2DM is expected to increase by more than 20% from (2018 to 2030). Diabetes may also occur during pregnancy (gestational diabetes) or may develop because of diseases of the pancreas, endocrine diseases, infections, drugs, immune disorders or genetic syndromes.


insulin
Credit: Unsplash/CC0 Public Domain

Even 100 years after its discovery, access to insulin still remains a challenge for many populations around the globe. Barriers to access mainly relate to affordability and availability, with costs, also related to associated necessary medical devices (e.g. test?stripes, syringes, pens), placing a large burden on patients and healthcare systems healthcare systems. For people with T1DM, the goal of insulin therapy is to provide insulin that mimics physiological insulin secretion in order to achieve near?normal glycaemic levels. Insulin is most commonly administered by subcutaneous injection. Insulin is usually applied through insulin syringes, insulin pens or insulin pumps. 

Recommendations by health authorities underline the fact that insulin is temperature sensitive and should be protected from heat and freezing conditions. The American Diabetes Association (ADA) publishes the following advice on its website (ADA 2021):  
“Although manufacturers recommend storing your insulin in the refrigerator, injecting cold insulin can sometimes make the injection more painful. To avoid this, many providers suggest storing the bottle of insulin you are using at room temperature. Insulin kept at room temperature will last approximately one month. Remember though, if you buy more than one bottle at a time to save money, store the extra bottles in the refrigerator. Then, take out the bottle ahead of time so it is ready for your next injection. Here are some other tips for storing insulin:

  • Do not store your insulin near extreme heat or extreme cold.
  • Never store insulin in the freezer, direct sunlight, or in the glove compartment of a car.
  • Check the expiration date before using, and don’t use any insulin beyond its expiration date.
  • Examine the bottle closely to make sure the insulin looks normal before you draw the insulin into the syringe.”

Manufacturers’ specifications recommend to keep insulin away from sunlight, not to freeze it, and store it in a refrigerator or at ‘room temperature’, usually not exceeding 25 °C or 30 °C. Nevertheless, room temperature may be defined differently in various parts of the world. Intact vials of insulin should be stored at low temperatures, i.e. between 2 °C and 8 °C, requiring affordable and reliable refrigeration. However, refrigeration may not be available or possible in various parts of the world. Moreover, unlike pharmaceutical refrigerators, household refrigeration may be unreliable and temperatures can drop below the freezing point. Once opened, a vial or cartridge can be stored at ambient temperature and used for approximately four to six weeks. The contents of the vial or cartridge are technically no longer sterile, and it is recommended to use the insulin in as short a time as possible to minimise concerns about potential microbiological contamination once the container has been opened or punctured. 

For millions of people with diabetes living in low- and middle-income countries, however, the harsh reality is that electricity and refrigeration are luxuries that are unavailable to them. Vulnerable populations in war-torn areas, disaster-prone regions, and climate crisis-affected areas, including those enduring extreme heat, also need solutions that don’t rely on powered fridges.

The new review summarizes results of different studies investigating what happens to insulin when stored outside of fridges, including previously unpublished data from manufacturers. The review found that it is possible to store unopened vials and cartridges of specific types of human insulin at temperatures of up to 25°C for a maximum of six months, and up to 37°C for a maximum of two months, without any clinically relevant loss of insulin activity.

Data from one study showed no loss of insulin activity for specific insulin types when stored in oscillating ambient temperatures of between 25°C and 37°C for up to three months. This fluctuation resembles the day-night temperature cycles experienced in tropical countries.

The research team, led by Bernd Richter from the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University in Düsseldorf, Germany, conducted comprehensive research to investigate insulin stability under various storage conditions. The review analyzed a total of 17 studies, including laboratory investigations of insulin vials, cartridges/pens, and prefilled syringes, demonstrating consistent insulin potency at temperatures ranging from 4°C to 37°C, with no clinically relevant loss of insulin activity.

Richter stressed the significance of this research, particularly for people living with type 1 diabetes, where “insulin is a lifeline, as their very lives depend on it. While type 2 diabetes presents its challenges, type 1 diabetes necessitates insulin for survival. This underscores the critical need for clear guidance for people with diabetes in critical life situations, which many individuals lack from official sources.”

“Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being.”

These findings can help communities facing challenges in securing constant cold storage of insulin. They provide reassurance that alternatives to powered refrigeration of insulin are possible without compromising the stability of this essential medicine. It suggests that if reliable refrigeration is not possible, room temperature can be lowered using simple cooling devices such as clay pots for insulin storage.

The researchers have also identified uncertainties for future research to address. There remains a need to better understand insulin effectiveness following storage under varying conditions. Further research is also needed on mixed insulin, influence of motion for example when insulin pumps are used, contamination in opened vials and cartridges, and studies on cold environmental conditions.

More information: Thermal stability and storage of human insulin, Cochrane Database of Systematic Reviews (2023). DOI: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015385