The many Cochrane Reviews related to the use of insulin for people with diabetes were added to in November 2023 with a new review of the thermal stability and storage of human insulin. Here's Bernd Richter, lead author and Emeritus Coordinating Editor of the Cochrane Metabolic and Endocrine Disorders Group, based in Düsseldorf, Germany, to tell us what they found.
Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. The many Cochrane Reviews related to the use of insulin for people with diabetes were added to in November 2023 with a new review of the thermal stability and storage of human insulin. Here's Bernd Richter, lead author and Emeritus Coordinating Editor of the Cochrane Metabolic and Endocrine Disorders Group, based in Düsseldorf, Germany, to tell us what they found.
Bernd: Many people with diabetes have to inject insulin every day, and there are various regulations and guidance on how the vials or cartridges should be transported and stored. For example, it's recommended that insulin be kept away from sunlight, stored in a refrigerator and not frozen. Unopened insulin should be stored between 2 °C and 8 °C, and in-use insulin vials or cartridges can be stored at 'room temperature' and should be used within four to six weeks. However, there is no clear consensus on how to store human insulin if reliable refrigeration is not available. This leads to uncertainty for many people with diabetes who live in places with little access to healthcare services or in low- and middle-income countries where most families don't have electric power or refrigeration facilities in their homes. Things get even more complicated for locations affected by disasters, periods of extreme heat due to the climate crisis or war-like conditions.
We wanted to evaluate the eﬀects of storing human insulin above or below the manufacturers' recommended temperature, using unopened or in-use containers for longer than advised, or both. We searched medical databases and contacted study authors and pharmaceutical manufacturers for relevant studies, and found only one small clinical study but several laboratory studies. This lack of clinical research is probably because of the difficulty of doing a study in either healthy volunteers or people with diabetes using human insulin that has not been stored according to the recommendations. There were nine laboratory studies of the storage of insulin vials, three for insulin cartridges and four for preﬁlled plastic insulin syringes, which are prepared by caregivers and are important for people with visual or manual impairments. All the studies looked at hot environmental conditions and there were no studies of insulin pumps.
The clinical study investigated insulin stored for six weeks in a refrigerator and in an unglazed clay pot, which reduced outside temperatures to around 25 °C to 27 °C. It included eight healthy volunteers and found that insulin from the clay pot had similar glucose-lowering activity to insulin from a refrigerator.
Nine of the laboratory studies examined unopened vials and cartridges and, in the studies with no clinically relevant loss of insulin activity, the storage was for up to four months at temperatures from 29 °C to 37 °C. Two studies reported a more pronounced loss of insulin activity after one to four weeks at 37 °C. The four studies of storing opened vials and cartridges at up to 37 °C for up to 12 weeks showed no clinically relevant reduction in insulin activity.
Two studies analysed storage at oscillating temperatures between 25 °C and 37 °C for up to 12 weeks, to imitate day- and night-time ﬂuctuations in tropical countries. There was no loss of insulin activity for short-acting, intermediate-acting or mixed insulin, which is a combination of short-acting and intermediate-acting human insulin.
One study on closed vials, one on opened vials, and two on preﬁlled syringes investigated insulin sterility and reported no bacterial contamination.
Finally, three manufacturers (BIOTON, Novo Nordisk, Elli Lilly and Company) provided us with unpublished data on temperature and storage conditions. This showed that only small amounts of insulin activity were lost if unopened vials or cartridges were stored at up to 25 °C for a maximum of six months or at up to 37 °C for a maximum of two months.
In summary: an increasing proportion of the global diabetes community lives in settings with poor or no access to healthcare facilities or refrigeration. In these circumstances, data from pharmaceutical companies indicate that unopened short-acting and intermediate-acting human insulin vials or cartridges can be stored at up to 25 °C for six months and at up to 37 °C for two months without a clinically relevant loss of insulin potency. Also, storage for up to three months at temperatures resembling day- and night-time ﬂuctuations in tropical countries does not result in a clinically relevant loss of insulin activity of short-acting, intermediate-acting or mixed human insulin. Importantly, even without access to reliable refrigeration, there are simple ways to prevent insulin from overheating, such as placing it inside clay pots ﬁlled with water or wet sand.
Turning to the future, clinical studies of insulin pharmacodynamics are needed to measure insulin potency and safety after varying storage conditions in human volunteers and people with diabetes. More studies are also needed on mixed insulin, as well as on opened vials and cartridges, to investigate potential microbial contamination after multiple punctures of the container. Studies on cold environmental conditions and insulin pumps are also required. Finally, manufacturers of human insulin should provide thermostability data to drug approval authorities to support updates on storage recommendations for human insulin.
Mike: To access the full details available in this review and to watch for future updates if new studies become available, just go to Cochrane Library dot com and search 'storage of insulin'.