Hi, I am using DO 12.21 with a high-DPI monitor (QHD) as my primary display, scaled at 150%, and all is fine. I also have two Full HD monitors, and DO does not seem to scale down when I shift it to either of these, and so everything in DO is too large. From what I understand it should be able to cope with this. I have tried rebooting and this does not help. Other programs are scaling Ok as they should.
Windows should scale it down, if the displays have different scaling amounts configured in the OS, and as long as you haven't turned on any DPI behavior overrides in the Properties dialog for dopus.exe.
(That said, I really wouldn't recommend running a mixture of DPIs at once as it introduces a number of OS bugs. It's best to stick to monitors which are all the same as each other, unfortunately.)