Abstract
INTRODUCTION: A step-up strategy for dipeptidyl peptidase (DPP)-4 inhibitor-based regimens has not yet been established. In addition, similarities and differences between DPP-4 inhibitors and glucagon-like peptide (GLP)-1 receptor agonists remain to be elucidated in humans. We investigated the pleiotropic effects of vildagliptin vs liraglutide in patients with type 2 diabetes on sitagliptin-based regimens in an open-label, randomized, clinical trial. MATERIALS AND METHODS: A total of 122 patients with type 2 diabetes that was inadequately controlled by sitagliptin-based regimens were randomly assigned to either vildagliptin (50 mg, twice daily) or liraglutide treatment (0.9 mg, once daily) for 12 weeks. The primary outcomes were glycated hemoglobin and body mass index. RESULTS: Both vildagliptin and liraglutide significantly lowered glycated hemoglobin within 12 weeks after switching from sitagliptin, but liraglutide produced a greater reduction (-0.67 ± 0.12% vs -0.36 ± 0.53%). Liraglutide lowered body mass index, whereas vildagliptin did not affect body mass index. Vildagliptin lowered fasting C-peptide immunoreactivity, but liraglutide did not. Vildagliptin increased serum levels of adiponectin, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, whereas liraglutide had no effect on these levels. Quality of life, assessed using the diabetes treatment satisfaction questionnaire, was not impaired in either group. The most common adverse events were gastrointestinal symptoms, which occurred with similar frequencies in both groups. CONCLUSIONS: Vildagliptin-mediated improvements in glycemic control did not correlate with indices for insulin secretion and insulin sensitivity. Switching from sitagliptin to liraglutide is useful in managing hyperglycemia and weight. Each agent exerts unique pleiotropic effects. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (no. 000004953).