Abstract
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 β-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, mean urinary albumin excretion (measured as urinary albumin-to-creatinine ratio) was markedly decreased, but no changes in estimated glomerular filtration rate were seen throughout the study. Beta-cell function as evaluated by homeostatic model assessment of β-cell function 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: These observations suggest 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 01 November (retrospectively registered): https://upload.umin.ac.jp/UMIN000038459.