Primary immune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease that could manifest with comorbid type 2 diabetes mellitus (T2DM). However, the exact impact of T2DM in patients with ITP remains uncertain. In this study, we performed a retrospective cohort study of 458 participants with ITP. The prevalence of T2DM was 7.6% in this population (35 patients), which was slightly lower than the Chinese nationwide prevalence of T2DM, calculated to be approximately 10.9%.The participants with pre-existing T2DM displayed a significantly higher response to therapy than those without T2DM (71% vs. 53%). Furthermore, in the T2DM cohort, the response rate reached 88% when metformin was included in the treatment regimen. This clinical evidence suggests that metformin therapy might improve the clinical outcomes of ITP.

Summary Immune thrombocytopenia (ITP) is an acquired autoimmune disease, in which the imbalance of CD4+ T cell subsets play a key role in the pathogenesis. Since T cells highly depend on metabolism for their function, we hypothesized that T cell dysfunction may be due to intracellular metabolic reprogramming. We found that in ITP, T cell metabolism shifts from oxidative phosphorylation to glycolysis. Empagliflozin, a sodium–glucose cotransporter 2 inhibitor, has shown regulatory metabolic effects on proximal tubular epithelial cells and cardiac cells beyond glucose lowering. However, the effects of empagliflozin on T cells remain unknown. To further investigate the metabolic dysfunction of CD4+ T cells in ITP, we explored the effect of empagliflozin on CD4+ T‐cell differentiation in ITP. Our results are the first to show that increased glycolysis in CD4+ T cells resulted in an unbalanced CD4+ T‐cell population. Furthermore, empagliflozin can affect the differentiation of CD4+ T‐cell subsets by inhibiting Th1 and Th17 cell populations while increasing Tregs. Empagliflozin appears to regulate CD4+ T cells through inhibiting the mTOR signal pathway. Considering these results, we propose that empagliflozin could be used as a potential therapeutic option for ITP by modulating metabolic reprogramming in CD4+ T cells.