You might want to start by running a shrink on the database to clean up any white space that you may have if you don't already have a database maintenance process taking care of this. Also, if you database is that big I would be curious to see what your data summarization frequencies are? If you are keeping data at to detailed of a level for too long this can happen. Lastly, check your Syslog and Trap tables and see what the size of those are; these tables can easily grow out of control if you are storing too much data for too long.
Hope this helps; post back here with what you find and the rest of the community and I will definitely try and help.