Device mount detection (USB or otherwise) is a feature request where someone had a partial solution that used an event to start a task which ran Duplicati. If your scripting is good, you could probably build on that. Using Duplicati from the Command Line runs independently from GUI tasks, so be careful to avoid collision.
One thing that sounds nice about that arrangement is that it should avoid the sometimes-extremely-slow database Recreate that would be required if the local DB is lost along with the rest of the source system, however that nice “all-in-one” package might also (as you suggested) offer you “nothing-at-all” without it.
Duplicati runs into somewhat similar bumps with cloud storage systems that use “cold storage”, meaning destination files aren’t instantly available. There are probably some forum posts about that, but taking a further step, and not even having the database there might get Duplicati more upset. Happy testing. 