Ten-year Follow-up of Sitagliptin Treatment in Type 2 Diabetes Mellitus Patients

Background: Early and effective intervention with a dipeptidyl peptidase 4 inhibitor (DPP4i) before the development of advanced atherosclerosis in type 2 diabetes mellitus (T2DM) patients without a history of cardiovascular disease (CVD) is reported to increase the chance of significant reductions in not only microvascular disease, but also CVD. Method: This study aimed to investigate whether sitagliptin is effective and tolerated for glycemic control and whether renoprotective effects and b-cell function are preserved for as long as ten years in Japanese patients with T2DM without a history of CVD. Results: : The situation is equivalent to improving glycemic control as assessed by hemoglobin A1c both in a sitagliptin group (sitagliptin 50 mg as either monotherapy or combination therapy with other oral glucose-lowering drugs (n=17)) or a control group (placebo as either monotherapy or combination therapy with other glucose-lowering drugs (n=9)), while anti-inflammatory effects as assessed by high-sensitivity C-reactive peptide in the sitagliptin group were superior to those in the control group. In the sitagliptin group, the mean values of urinary albumin excretion measured as urinary albumin-to-creatinine ratio (ACR) were markedly decreased, but no changes in estimated glomerular filtration rate (eGFR) were seen throughout the study. Beta-cell function as evaluated by homeostatic model assessment of b-cell function (HOMA-β) values was reduced at baseline in both groups, improved significantly in the sitagliptin group, and continued unchanged in the control group during the study. Conclusion: This observation suggests that early intervention with sitagliptin in patients with T2DM may have long-lasting renoprotective and islet-protective effects. Trial registration: UMIN Clinical Registry (UMIN000038459). Registered 01November (Retrospectively registered), https://upload.umin.ac.jp/UMIN000038459