OBJECTIVES The aim of this study was to analyze trends and potential risks of combined use of silymarin and hypoglycemic drugs in a Taiwanese population. METHODS Data for this retrospective and descriptive population-based study were retrieved from the Taiwan National Health Insurance Research Database representing 200,000 sampling beneficiaries enrolled in the program in the year 2000. The prescription details of ambulatory care orders were retrieved for 2000 to 2006. The extent of co-prescription of silymarin and hypoglycemic drugs and associations with patient characteristics, hospital type, and co-morbid chronic diseases were assessed, including an analysis using the many-faceted Rasch model. RESULTS Silymarin prescriptions increased from 0.17% (860/515765) in 2000 to 0.76% (2335/309053) in 2006. Silymarin combined with hypoglycemic drugs was mostly prescribed to patients 60 years or older. Among this group, the percentage of prescriptions with silymarin alone increased about four-fold, from 245 in 2000 to 1022 in 2006. The number of co-prescriptions in the same age group also increased in the same period from 11 (15.49%) to 206 (58.8%). Most prescriptions were prescribed for 28 days. Of the combined prescriptions, 42% were prescribed at the same ambulatory care visit. Co-prescription of silymarin and hypoglycemic drugs correlated with patient characteristics, physician specialty, antidiabetic type, and other confounders. CONCLUSIONS There was a trend to increase of co-prescription of silymarin and hypoglycemic drugs in Taiwan's elderly population from 2000 to 2006. Physicians should take particular care in adjusting the dose of hypoglycemic drugs when prescribing these drugs and silymarin concurrently in this age group.