Aims To compare the occurrence of cerebral, cardiovascular, and renal events in patients with hyperuricaemia treated with febuxostat and those treated with conventional therapy with lifestyle modification. Methods and results This multicentre, prospective, randomized open-label, blinded endpoint study was done in 141 hospitals in Japan. A total of 1070 patients were included in the intention-to-treat population. Elderly patients with hyperuricaemia (serum uric acid >7.0 to ≤9.0 mg/dL) at risk for cerebral, cardiovascular, or renal disease, defined by the presence of hypertension, Type 2 diabetes, renal disease, or history of cerebral or cardiovascular disease, were randomized to febuxostat and non-febuxostat groups and were observed for 36 months. Cerebral, cardiovascular, and renal events and all deaths were defined as the primary composite event. The serum uric acid level at endpoint (withdrawal or completion of the study) in the febuxostat ( n = 537) and non-febuxostat groups ( n = 533) was 4.50 ± 1.52 and 6.76 ± 1.45 mg/dL, respectively ( P < 0.001). The primary composite event rate was significantly lower in the febuxostat group than in non-febuxostat treatment [hazard ratio (HR) 0.750, 95% confidence interval (CI) 0.592–0.950; P = 0.017] and the most frequent event was renal impairment (febuxostat group: 16.2%, non-febuxostat group: 20.5%; HR 0.745, 95% CI 0.562–0.987; P = 0.041). Conclusion Febuxostat lowers uric acid and delays the progression of renal dysfunction. Registration ClinicalTrials.gov (NCT01984749).

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This study is a prospective randomized open-label blinded endpoint study. Patient enrolment was started in November 2013 and was completed in October 2014. The patients will be followed for at least 3 years. The primary endpoint is a composite of cerebral, cardiovascular, and renal events, and all deaths including death due to cerebral, cardiovascular, and renal disease, new or recurring cerebrovascular disease, new or recurring non-fatal coronary artery disease, cardiac failure requiring hospitalization, arteriosclerotic disease requiring treatment, renal impairment, new atrial fibrillation, and all deaths other than cerebral or cardiovascular or renal disease. These events will be independently evaluated by the Event Assessment Committee under blinded information regarding the treatment group. The study was registered at ClinicalTrials.gov with the identifier NCT01984749.

BackgroundPostprandial hyperglycemia and hyperlipidemia are highly related to the development of atherosclerosis. Sodium/glucose cotransporter-2 (SGLT2) inhibitors have attracted attention as a new class of anti-diabetic agents for the treatment of type 2 diabetes. We investigated the effect of tofogliflozin on postprandial glucose and lipid metabolism in Japanese male patients with type 2 diabetes.MethodsTen Japanese men with type 2 diabetes (average age 66.3 years) were orally administered tofogliflozin (20 mg per day) for 8 weeks followed by a subsequent 8 weeks of washout of the agent. At 0, 8 and 16 weeks, postprandial metabolic parameters were measured at 0, 60 and 120 min after cookie ingestion.ResultsThere were significant reductions in body weight and body mass index at 8 weeks. There was a reduction in HbA1c at 8 weeks, which returned to pretreatment levels at 16 weeks. Serum insulin levels did not change during the entire study period under either fasting or postprandial state. The area under the curve of plasma glucagon significantly increased at 8 weeks. There were no changes in lipid and lipoprotein levels either in fasting or postprandial state except for tendency toward reduction in postprandial triglycerides at 8 weeks and increase in HDL-C at 16 weeks.ConclusionsTofogliflozin treatment causes an improvement of postprandial glucose metabolism but not considerable postprandial lipid metabolism.

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