The issue is polygonal rifling not unsupported chambers
First, I had a G21 years ago and loved it except for the fat grips. That is the only reason I traded it away. I have fairly large hands but it was just a bit too wide. I now have a SIG P245 and SA 1911 in .45 ACP. And switched to a G23 for a Glock pistol.
Now then, the .45 ACP has NO ISSUES with unsupported, or "less supported" chambers. That is why SAAMI keeps the max pressure so low on the .45 ACP. It was originally intended for the 1911 which probably sets the standard for "unsupported chambers." That is why the .45 Super came along. Alll it does is thicken the case web to handle higher pressures in a standard 1911 barrel/chamber.
The extent of chamber support, and it does vary by manufacturer and model, is only a factor for higher pressure cartridges such as the 10mm, .40 S&W, .357 SIG, etc. There is a lot of talk about this, but I reload lots of .40 shot out of SIG P229 and G23. The sizing die puts everything in place and I keep an eye out for case failure signs (none so far), like I do for all my cartridges. But you weren't asking about the .40, it was the .45 ACP.
The only issue with the G21 and reloading would be lead bullets. Big deal. Buy an aftermarket barrel with standard cut or broached rifling.
Or just reload jacketed bullets. That is what I did when I reloaded for my G21 and aftermarket barrels were not commonly available.
$400 is a can't lose deal on a G21. If you think you can be comfortable with a fat grip then go for it. Just plan to reload jacketed bullets or get a third party barrel if you want to shoot a load of lead.
But, unsupported barrels have no bearing whatsoever in reagards to any .45 ACP pistol. Period.