Study: Insulin Shelf Life Could Be 4 Times Longer than Previously Reported

Gun Forsander, MD, PhD
Credit: University of Gothenburg

A new study from an international team of investigators suggests the shelf life of some insulin products could be 4 times longer than previously thought.

A pilot study assessing the lifespan of potency for 6 different insulin preparations when stored at room temperature, results of the study indicate unrefrigerated insulins could be sufficiently thermostable for 2 months and possibly up to 4 months.

“This study shows that insulin probably has a considerably longer shelf life at room temperature — up to 4 times as long as was previously believed. The study also showed that the simple solution, with cooling clay pots, can be helpful when the weather’s at its hottest,” said Gun Forsander, a researcher in pediatrics at Sahlgrenska Academy of University of Gothenburg and a pediatrician at Sahlgrenska University Hospital.

Few agents in medicine have garnered as much public attention as insulin. The demonstration of insulin’s effects as a treatment for type 1 diabetes in 1922 was welcomed with a Nobel Prize.³ In more recent times, insulin has been in the spotlight for being emblematic of the impact of rampant rises in cost for pharmaceutical products on the quality of life for people dealing with chronic illness.

In October 2022, data from the 2021 National Health Interview Survey was published and revealed 16.5% of insulin users reported rationing insulin when asked if they had “skipped insulin doses”, “took less insulin than needed”, or “delayed buying insulin” in the interest of saving money. Among those with type 1 diabetes, this figure rose to 18.6% and, among those with type 2 diabetes, this figure rose to 19.2%.⁴ In March 2023, insulin users welcomed news of significant changes in the list prices for insulin products from Eli Lilly and Company, Sanofi, and Novo Nordisk, which represents perhaps the most significant milestone in the fight for equitable insulin access in decades for US insulin users.⁵

In the current study, Forsander and a team of colleagues from institutions based in Europe, the US, Australia, and India sought to develop a more thorough understanding of the potency of insulin products in real-world settings and whether storage settings might influence changes in potency. Of note, the specific settings of interest for storage were outside and within clay pots using evaporative cooling.¹

For the purpose of analysis, investigators chose 100 IU/mL insulins (vials of human soluble; Eli Lilly), human isophane (Eli Lilly), and human soluble-isophane (30:70; Novo Nordisk); and 3 mL cartridges of insulin aspart (Novo Nordisk), and two preparations of insulin glargine (Sanofi and Eli Lilly) as products of interest. These insulins were stored unopened in a real-world for 1-4 months in non-refrigerated conditions during the summer in India. For the purpose of analysis, these were later compared against control samples of each insulin, which remained refrigerated for the duration of the study.¹

Per study protocol, 6 families with a person younger than 25 years of age with insulin-requiring diabetes were given 2 different types of insulin. Vials were stored in watertight bags and the bags were placed in an open plastic container to be stored on a high shelf or in a cupboard or in clay pots with a separate water compartment. Control samples were stored at theDiabetes Research Education and Management (DREAM) Trust. Analyses of insulin potency were done at the University of Florida with high-performance liquid chromatography and at the University of Gothenburg with nuclear magnetic resonance spectroscopy.¹

Results from the investigators analysis of storage conditions indicated monthly mean open box temperate across the families ranged from 29.4-32.0 °C, with mean maximum temperatures of 30.4-34.9 °C and meanminimum temperatures of 28.3-29.8 °C. Investigators pointed out use of clay pots appeared to significantly reduced temperatures, with a mean difference in temperature of 2.6 °C. (SD, 2.8, range 0.4-5.7; P<.0001) in ten of the 12 clay pots.¹

In the analyses performed at the University of Florida, all human insulin samples maintained 95% or more of the refrigerated potency except for one vial each of human soluble, human soluble-isophane (30:70), and human isophane (range, 92.4-94.1%) at 4 months. Results suggested clay pot storage results in less decline in relative potency compared with refrigerated samples at 4 months than open box storage (0.5% vs 3.6%; P=.001).¹

In the analyses performed at the University of Gothenburg, investigators pointed out there was an apparent subtle line width increase and slight peak shifts, which correlated with storage time for non-refrigerated samples. Results indicated acceptable insulin concentrations were maintained up to 2 months for all samples of all insulin preparations and all samples from 3 analogue insulin preparations and 3 of 4 samples for each of the human insulins maintained a relative concentration of 95% or more at 4 months.¹

“If our results can be confirmed in larger studies, it may drive a change in the requirement to discard insulin kept outside a fridge after one month. The period when insulin may still be used can potentially, in that case, be extended to three or perhaps even four months. That would have a major bearing on the resource-weak families’ access to insulin,” said Graham D Ogle, MBBS, director of the ‘Life for a Child’ organization and adjunct professor at the University of Sydney.²

References

1. Pendsey S, James S, Garrett TJ, et al. Insulin thermostability in a real-world setting [published online ahead of print, 2023 Mar 29]. Lancet Diabetes Endocrinol. 2023;S2213-8587(23)00028-1. doi:10.1016/S2213-8587(23)00028-1
2. University of Gothenburg. Longer shelf life for insulin has major bearing on Global Health. https://www.expertsvar.se/en/pressmeddelanden/longer-shelf-life-for-insulin-has-major-bearing-on-global-health/. Published April 11, 2023. Accessed April 12, 2023.
3. Campbell P. The age of teplizumab: A new era in type 1 diabetes. HCP Live. https://www.hcplive.com/view/the-age-of-teplizumab-a-new-era-in-type-1-diabetes. Published December 14, 2022. Accessed April 12, 2023.
4. Gaffney A, Himmelstein DU, Woolhandler S. Prevalence and Correlates of Patient Rationing of Insulin in the United States: A National Survey. Ann Intern Med. 2022;175(11):1623-1626. doi:10.7326/M22-2477
5. Isaacs D, Bellini N. Diabetes dialogue: 10 years of sglt2s, insulin for all, and Pemvidutide. HCP Live. https://www.hcplive.com/view/diabetes-dialogue-10-years-of-sglt2s-insulin-for-all-and-pemvidutide. Published March 29, 2023. Accessed April 12, 2023.