The aim of this retrospective cohort study is to assess the cumulative development incidence and predictive factors for type 2 diabetes (T2DM) in HCV positive and hypertensive patients treated with losartan. Eighty Japanese patients were given 50 mg of losartan per day after diagnosis of hypertension (losartan group). Another 160 treated with spironolactone were selected as control (spironolactone group). Patients in spironolactone group were matched 1:2 with losartan group for age and sex. The mean observation period was 5.2 years in losartan group and 5.4 years in spironolactone group. An overnight (12 hr) fasting blood sample ora casual blood sample was taken for routine analyses during follow-up. The primary goal is the onset of T2DM. Evaluation was performed by using the Kaplan-Meier method and the cox proportional hazards analysis. Three patients in losartan group and 20 in spironolactone group developed T2DM. The 5th year cumulative appearance rates of T2DM were 5.4% in losartan group and 14.4% in spironolactone group. Multivariate cox proportional hazards analysis showed that T2DM development after the initiation of anti-hypertensive drugs occurred when anti-hypertensive drug was spironolactone (hazard ratio: 6.10; 95% confidence interval = 1.78-20.84; P = 0.004), histological staging was advanced (hazard ratio: 4.31; 95% confidence interval = 1.94-9.60; P < 0.001), fatty liver was present (hazard ratio: 3.28; 95% confidence interval = 1.47-7.27; P = 0.004), and patient had pre-diabetes (hazard ratio: 2.47; 95% confidence interval = 1.08-5.63; P = 0.032). Our results indicate losartan causes about 60% reduction of the onset of T2DM compared to patients treated with spironolactone. J. Med. Virol. 81:1584-1590, 2009. (C) 2009 Wiley-Liss, Inc.