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There’s a number of things to consider when looking at wheels. The larger the wheel diameter, the more energy to get it spinning. There’s also bearing and road friction. One thing that would reduce drag would be to make the tire and rim narrower but the trade off would be weight capacity.

Wow, I never thought about that before, but I guess that's why the tires on horse-racing sulkies are very skinny -- and on racing bicycles.
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As far as wind drag, has anybody ever come up with a way to make the rig more aerodynamic for trailering?