Four-year clinical remission of type 1 diabetes mellitus in two patients treated with sitagliptin and vitamin D3

Abstract

SummaryType 1 diabetes mellitus (T1DM) is a chronic disease characterized by autoimmune destruction of pancreatic beta cells and inadequate insulin production. Remission criteria in T1DM take into account serum levels of C-peptide and glycosylated hemoglobin, as well as the dose of insulin administered to the patient. However, remission of T1DM lasting longer than 1 year is rare. We describe here the cases of two young women who presented with positive glutamic acid decarboxylase (GAD) antibody and classic clinical manifestations of T1DM. Both patients had a prior history of Hashimoto’s thyroiditis. They were initially treated with a basal-bolus regimen of insulin (glargine and lispro/glulisine). Once their blood glucose levels were controlled, they were started on oral sitagliptin 100 mg and vitamin D3 5000 IU daily. After this therapy, both patients achieved clinical diabetes remission for 4 years, along with a decrease in anti-GAD antibody levels. These benefits were probably associated with immunological effects of these medications. Inhibition of dipeptidyl peptidase 4 (DPP-4) in animal models deregulates Th1 immune response, increases secretion of Th2 cytokines, activates CD4+CD25+FoxP3+ regulatory T-cells and prevents IL-17 production. Vitamin D3 also activates CD4+CD25+FoxP3+ regulatory T-cells, and these medications combined can improve the immune response in patients with new-onset T1DM and probably promote sustained clinical remission.Learning points:The use of sitagliptin and vitamin D3 in patients with new-onset type 1 diabetes mellitus (T1DM) may help decrease the daily insulin requirement by delaying beta cell loss and improving endogenous insulin production.The use of sitagliptin and vitamin D3 in new-onset T1DM could help regulate the imbalance between Th17 and Treg cells.Age 14 years or above, absence of ketoacidosis and positive C-peptide levels in patients with T1DM are good criteria to predict prolonged T1DM remission.The determination of anti-GAD antibodies and C-peptide levels could be helpful in the follow-up of patients in use of sitagliptin and vitamin D3, which could be associated with prolonged T1DM clinical remission.

Possible Long-Term Efficacy of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, for Slowly Progressive Type 1 Diabetes (SPIDDM) in the Stage of Non-Insulin-Dependency: An Open-Label Randomized Controlled Pilot Trial (SPAN-S)

“…Recently, based on the potential beneficial effects of DPP-4 inhibitors and the promising results in animal studies, DPP-4 inhibitors have been clinically tested in patients with T1D or SPIDDM/LADA. Favorable effects of sitagliptin were suggested in several cases with T1D [ 30 ] or SPIDDM/LADA [ 31 , 32 ]; very recently, 4-year clinical remission of T1D in two young patients treated with sitagliptin and vitamin D3 were reported [ 33 ]. However, the results of clinical trials for T1D patients have been conflicting and appear to be inconclusive [ 34 – 36 ].…”

Influence of Vitamin D on Islet Autoimmunity and Beta-Cell Function in Type 1 Diabetes

“…The efficacy of DPP-4 inhibitors as additional anti-hyperglycemic agents for the management of T1D has also been investigated, although the results remain unclear [202]. However, some case studies showed a potential efficacy of cholecalciferol in combination with the DPP-4 inhibitor sitagliptin in sustaining clinical remission in new-onset T1D [203], as well as insulin independence in LADA [204]. The rationale for such combination therapy in autoimmune diabetes may essentially consist in the synergism between the DPP-4 inhibition-mediated effects on pancreatic endocrine cells (reduction in glucagon secretion from alfa cells, increase in insulin secretion from beta cells, and potential stimulation of beta-cell proliferation) and the immunomodulatory effects exerted by both vitamin D and DPP-4 [205].…”

Altered T‐cell subsets and transcription factors in latent autoimmune diabetes in adults taking sitagliptin, a dipeptidyl peptidase‐4 inhibitor: A 1‐year open‐label randomized controlled trial

“…Case reports and clinical trials in autoimmune diabetes treated with DPP‐4 inhibitor alone or in combination with other drugs showed that sitagliptin significantly improved glycemic control and reduced insulin requirements, accompanied by a good tolerance profile. Although a recent meta‐analysis showed that DPP‐4 inhibitor gives a neutral result for HbA1c in type 1 diabetes.…”