Association between sitagliptin plus vitamin D3 (VIDPP-4i) use and clinical remission in patients with new-onset type 1 diabetes: a retrospective case-control study

Abstract

Objective:The occurrence of partial remission (honeymoon phase) in type 1 diabetes (T1D) has been associated with a reduced risk of chronic microvascular complications of diabetes. We have published case reports showing that a combination therapy with the DPP-4 inhibitor sitagliptin plus vitamin D3 (VIDPP-4i) can prolong the honeymoon phase in patients with new-onset T1D. In the present case-control study, we investigated the frequency of occurrence of clinical remission (CR) in patients with new-onset T1D after VIDPP-4i treatment. Subjects and methods: In this case-control study, we collected data spanning 10 years from medical records of 46 patients (23 females) recently diagnosed with T1D. Overall, 27 participants with CR (insulin dose-adjusted glycated hemoglobin [IDAA1c] ≤ 9) at 12 or 24 months composed the case group, and 19 participants without CR served as the control group. Chi-square with Yates correction was used to analyze the association between VIDPP-4i use and CR, and odds ratio (OR) was used to determine the chance of CR due to VIDPP-4i treatment exposure. Results: In all, 37 patients (80.4%) experienced CR at some time over 24 months. The mean CR duration was 13.15 ± 9.91 months. Treatment with VIDPP-4i was significantly associated with CR. At 24 months, the OR of CR after VIDPP-4i exposure was 9.0 (95% confidence interval [CI] 2.21-30.18, p = 0.0036). Additionally, 9 (33.6%) and 4 (14.8%) patients in the VIDPP-4i group experienced insulin-free CR at 12 and 24 months, respectively. Conclusion: Therapy with VIDPP-4i was associated with a higher frequency and duration of the honeymoon phase. Randomized controlled trials are needed to confirm these findings.

Prevention and treatment of type 1 diabetes: in search of the ideal combination therapy targeting multiple immunometabolic pathways

“…However, among patients receiving ATG/G-CSF combination therapy, the most common worst-grade adverse events included lymphopenia (n = 15), decreased CD4 count (n = 15), hypoglycemia (n = 13), serum sickness (n = 13), and cytokine release syndrome (n = 11) [39] . Recently, promising results (in terms of prevention of T1D progression and preservation of endogenous insulin secretion) have also been observed from the off-label use of low-dose ATG in children aged 5-14 years with stage 2 T1D followed for 18-48 months [40] .…”

Benefits and risks of drug combination therapy for diabetes mellitus and its complications: a comprehensive review

“…This combination therapy has the potential to preserve β cell function in individuals with T1D ( 64 – 66 ). In a retrospective case-control study, it was observed that the combination of vitamin D plus DPP-4 inhibitors could notably prolong the honeymoon phase (partial remission of disease) in newly diagnosed T1D ( 50 ). However, further clinical trials are needed to confirm the potential role of this combination therapy in the onset and progression of T1D.…”

Comment on Russell et al. Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked, Controlled Trial. Diabetes Care 2023;46:1005–1013

“…We believe that therapies aimed at interrupting the evolution of T1D should work together on the immune system and on the pancreatic islets ( 2 ). My group ( 3 ) and other authors have shown prolongation of the honeymoon phase and maintenance of C-peptide levels in T1D treated with dipeptidyl peptidase 4 inhibitors plus vitamin D3 (VIDPP-4i), with some patients not needing to be treated with insulin for up to 24 months. Promising results have been shown in NOD mice and humans treated with a combination of sitagliptin, γ-aminobutyric acid, and proton pump inhibitors, and some patients did not need to be treated with insulin for a long time ( 4 ).…”