I have found out that turning off MDS will hurt the fuel mileage slightly on the highway. I cruise 70mph for 35 miles everyday to and from work. While I haven't done a tank to tank comparison, I can tell that my EVIC will show roughly ~.5mpg drop in fuel mileage. If I am in the city, I turn it off, because the MDS lugs the motor quite often when off and on the gas.
IF you turn off MDS, I have also noticed on the 8 speeds at least, that the shift schedule for downshifting is a bit more aggressive. when coasting, it will make no difference that I can tell. BUT, if you are on the brakes, it's almost like the trans downshifts the exact same way as you are in tow/haul mode. Kinda weird, but whatever. I have a very basic truck and it's a RCSB, if turning off my MDS is affecting my fuel mileage, I KNOW it has to be affecting the QC and CC gas mileage as well on the highway. As far as city, I can't tell a difference, other than that I don't get the MDS drone.