I've been fiddling with these since the late 90's. The smarty is by far the safest off the shelf tune (if there is such a thing) for my gen vp44 I have seen. As mentioned the Smarty/ Edge CTS I think is the best plug and play combo too.

I didn't see a significant increase in mpg until I dropped in larger injectors, larger flow VP44, larger flow lift pump, cold air intake, larger exhaust and larger turbo. You can kinda see the theme there with the parts. My gen II cummins just rolled 260k and runs like a raped ape. I average 20.3 - 22.1 mpg depending on if I'm pulling my trailer more often through the mountains or just running to Wally World. Those numbers are with the stock turbo as well and when I ran a bigger turbo setup I gained another 1.2 on average. As items wore out I just replaced with stronger/better parts including my trans that can handle around 700 horses and I'll never come close to that. These stock 47re's in my gen tend to burn up quicker with hard shifts from a tuner hence the overkill.

The older the gen the more tuneable for mpg it is for sure. Once mine rusts out around my motor I won't buy anything beyond an early 07 with the 5.9. I managed a diesel shop here in Parker for a bit and all we saw constantly were Ford 6.0's and the Cummins 6.7's with the dpf/egr issues just eating up turbos all day long with only 20 - 70k in most instances.

After all these mods my MPG stays good only when I keep my foot out of it but what fun is that! If you happen to be this way come swing by and you can take my old girl for a spin.