Personally, I would go with the Model 21 in 0.45 ACP but reload with clad bullets. Although not a fully supported chamber, the 0.45 is not a high pressure round whereas the 0.40 is (relative terms), thus a slight overload in the 0.45 is not a problem, but it can be in a 0.40. My 0.40s are not Glocks but Brownings, Berettas and Walthers, all with fully supported chambers. dave_n