I've never tried this, but you might consider stopping the sim midway, and using the utility that clears the memory.
"IF" you are using Windows!
Realflow has a built-in utility for this, but I also have an external utility that clears the RAM when I click it. Part of my Advanced System Care product, I believe. I use this constantly in Maxwell Renders, and when I've been using Maya for hours on end. It helps a ton. I suspect that one or two clearings of the RAM would restore your sim speed. Windows has several internal processes that preserve RAM memories, but kind get choked up and are not strictly needed in large sims.
Discussions about the use of Realflow