I'll offer the benefit of my actual experience, rather than hypothetical pontificating about G21s. I've fired both .45 Supers and .450 SMCs through Glock 21s, with no problems. I did use the heaviest recoil spring that I could find. Tens of thousands of rounds later (but only a few hundred .45 Supers, etc.) and my trusty G21s are still spot-on.
I'd prefer an aftermarket barrel with a comp, eg., KKM, for shooting really hot ammo through Glocks.
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