ESPE Yearbook of Paediatric Endocrinology

World Health Organization, Geneva: 2021 (WHO/MHP/HPS/EML/2021.03) https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2021.03

Brief Summary: A major change in the World Health Organization (WHO) 2021 list of essential medicines (EML) is the inclusion, in both the EML for adults and for children, of long-acting analogues of insulin as therapeutic alternatives to human insulin (NPH)

Every 2 years, the WHO publishes a revised List of Essential Medicines for adults (EML, since 1977) and children (EMLc, since 2007). The EMLc applies to children up to 12 years. Human insulin (vials) has been included in the WHO EML since its first edition, in 1977. The most recent EML and EMLc, released in 2021, now include long-acting insulin analogues (insulins detemir, degludec and glargine) for potential inclusion in national EMLs. The addition of long-acting insulin analogues was proposed on several occasions over the last few years, but had always been rejected on the basis of an unfavourable cost benefit ratio. Several reviews have shown modest but definite clinical benefits (i.e. small decrease in HbA1c, decrease in nocturnal hypoglycemia) in patients with Type 1 diabetes, less so in patients with Type 2 diabetes (1, 2). The concern expressed by several experts in the field is that inclusion of long-acting analogues in the WHO EML could make insulin further out of reach for patients in LMICs (3). Indeed, especially in low- and middle-income countries, insulin analogues are much more expensive to the patient than human insulins, despite grossly similar manufacturing costs (4). However, in many high-income countries, where patients can afford insulin analogues, the reality is that pediatric endocrinologists are presently using insulin analogues as first line treatment.

In 2019, the WHO piloted a prequalification program for human insulin, with the hope that it would increase the number of players in the field (beyond the 3 major manufacturers, Sanofi, Novo Nordisk and Eli-Lilly, which together account for >95% of all insulin prescribed worldwide). Unfortunately, so far, prequalification of human insulin did not attract applications by new manufacturers. In May 2022, the International Consortium for Pediatric Endocrinology (ICPE, https://www.ncdchild.org/), following a recommendation by Global Pediatric Endocrinology and Diabetes (GPED, www.globalpedendo,org), wrote to WHO to request that prequalification of insulin be extended to insulin analogues. This process is now approved!

Finally, it is important to recognize that in parallel to the EML, WHO publishes a List of Essential Diagnostics (EDL). It includes tests that are essential for the management of diabetes and diabetes ketoacidosis, including basic chemistry, HbA1c and glucose monitoring (5).

References: 1. AC Tricco, HM Ashoor, J Antony, Z Bouck, M Rodrigues, PA Khan, V Nincic, N Darvesh, F Yazdi, M Ghassemi, JD Ivory, AA Veroniki, CH Yu, L Moja, SE Straus. Comparative efficacy and safety of ultra-long-acting, long-acting, intermediate-acting, and biosimilar insulins for Type 1 diabetes mellitus: a systematic review and network meta-analysis. J Gen Intern Med 36(8):2414–26. DOI: 10.1007/s11606-021-06642-7. 2. AA Shafie, CH Ng, YP Tan, N Chaiyakunapruk. Systematic review of the cost effectiveness of insulin analogues in Type 1 and Type 2 Diabetes Mellitus. Pharmacoeconomics 2017 Feb;35(2):141–162. DOI: 10.1007/s40273-016-0456-2. 3. D Beran, B Hemmingsen, JS Yudkin. Analogue insulin as an essential medicine: the need for more evidence and lower prices. Lancet Diabetes Endocrinol 2019, 7: 338 DOI: 10.1016/S2213-8587(19)30111-1.4. D Beran, M Lazo-Porras, CM Mba, JC Mbanya. A global perspective on the issue of access to insulin. Diabetologia 2021: 64;954–962. DOI: 10.1007/s00125-020-05375-2.5. The selection and use of essential in vitro diagnostics: report of the third meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2020 (including the third WHO model list of essential in vitro diagnostics). Geneva: World Health Organization; 2021 (WHO Technical Report Series, No. 1031).