Dapagliflozin’s impact on hormonal regulation and ketogenesis in type 1 diabetes: a randomised controlled crossover trial – Published online 09/07/2025

Andreas Gübeli, Nicole Steiner, Andreas Limacher, Déborah Mathis, Andreas Melmer & Markus Laimer

Sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated therapeutic benefits in individuals with type 1 diabetes but are also associated with an increased risk of diabetic ketoacidosis. In this issue, Gübeli and Steiner et al (https://doi.org/10.1007/s00125-025-06481-9) present results from a randomised crossover study of 13 adults with type 1 diabetes examining the effects of pairing the SGLT2 inhibitor dapagliflozin with standard insulin treatment on the hormonal determinants of glucose homeostasis and ketogenesis. Using rigorous clamp experiments to track hormones and ketones, the authors report that dapagliflozin lowered post-challenge glucose levels but did not change glucagon-like peptide 1, glucagon or somatostatin levels, suggesting the benefits of dapagliflozin are not driven by incretin or alpha cell effects. However, ketone levels rose under both test conditions, despite controlled glucose and standardised insulin, highlighting an intrinsic tendency toward ketogenesis. No diabetic ketoacidosis occurred; ketonaemia was mild and asymptomatic, yet frequent. The authors propose that dapagliflozin’s advantage may be related to insulin-sparing rather than hormonal effects, while elevated ketones remain an important potential safety signal. They conclude that selective use of dapagliflozin might be considered alongside education, ketone monitoring and clear sick-day rules.

All News