Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes

•Vitamin D and DPP-4 inhibitors exert synergistic anti-inflammatory and immunomodulatory actions.•Pre-clinical evidence suggests that vitamin D and DPP-4 inhibitors may prevent or delay the onset of diabetes or halt disease progression.•Vitamin D plus DPP-4i combination therapy (VIDPP-4i) has the potential ability to preserve beta-cell function in autoimmune diabetes.•Randomized controlled trials are warranted to establish the efficacy of VIDPP-4i as an immunomodulation therapy in autoimmune diabetes. Type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) represent the most common types of autoimmune diabetes and are characterized by different age of onset, degrees of immune-mediated destruction of pancreatic beta cells and rates of disease progression towards insulin dependence. Several immunotherapies aimed to counteract autoimmune responses against beta cells and preserve beta-cell function are currently being investigated, particularly in T1D. Preliminary findings suggest a potential role of combination therapy with vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors (VIDPP-4i) in preserving beta-cell function in autoimmune diabetes. This manuscript aims to provide a comprehensive overview of the immunomodulatory properties of vitamin D and DPP-4 inhibitors, as well as the rationale for investigation of their combined use as an immunomodulation therapy for autoimmune diabetes.