Nature Reviews Endocrinology, Published online: 06 January 2026; doi:10.1038/s41574-025-01220-xMany different models are used in research into diabetes mellitus, and each has strengths and limitations. In this Review, the authors explain several in vivo and in vitro models of hyperglycaemia and discuss how future models might be improved to better replicate physiological conditions in people with diabetes mellitus.