I can see two possibilities:
For a book that was copied to a Kobo from calibre and I want to delete both copies, I wait till the next time I connect to calibre, select the book to be deleted and then Remove selected books and select the Library and Device button.
For a book that was synced from Kobo to my ereader and then copied to calibre, I would delete it from the Kobo using it's GUI and keep the copy in calibre as a backup.
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