Complete loss of SLC30A8 in humans improves glucose metabolism and beta cell function – Published online 29/09/2025

Lindsey B. Lamarche, Christopher Koch, Shareef Khalid, Maleeha Zaman Khan, Richard Zessis, Matthew E. Clement, Daniel P. Denning, Allison B. Goldfine, Igor Splawski, Ali Abbasi, Jennifer L. Harrow, Christina Underwood, Kazuhisa Tsunoyama, Makoto Asaumi, Ikuyo Kou, Juan L. Rodriguez‑Flores, Alan R. Shuldiner, Asif Rasheed, Muhammad Jahanzaib, Muhammad Rehan Mian, Muhammad Bilal Liaqat, Usman Abdulsalam, Riffat Sultana, Anjum Jalal, Muhammad Hamid Saeed, Shahid Abbas, Fazal Rehman Memon, Mohammad Ishaq, Allan M. Gurtan, John E. Dominy, Danish Saleheen

Individuals who are completely deficient in a particular gene can expand our understanding of the gene’s biological function and, in the case of therapeutic development, provide insights into efficacy and safety associated with chronic inhibition. Heterozygous loss of SLC30A8 in humans has been previously shown to protect against type 2 diabetes but, to date, complete deficiency has yet to be described. In this issue, Lamarche et al (https://doi.org/10.1007/s00125-025-06530-3) report the identification and characterisation of the first known individuals with SLC30A8 deficiency. Complete loss of function was associated with reduced risk of type 2 diabetes, improved glucose-stimulated insulin secretion and no overt adverse phenotypes. The authors conclude that these results indicate that inhibition of SLC30A8, up to and including complete antagonism, is likely to be tolerated in humans and may be effective in preventing type 2 diabetes in at-risk populations or in treating existing patients.

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