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From what I understand and going by what I've read alot of airlines train their pilots to fly the long distance commercial flights as economically as possible while still following safety/airpsace protocol as required. They take into account altitude and air density at different heights for resistance and of course weather conditions, speed changes etc...
There are lots of variables but from all the airline things I've read I believe that they do work hard to take fuel economy into account and get the most out of their fuel.
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