It is not really necessary to upscale when drawing, but if you use a larger canvas and you scale down the image then errors will also be scaled down so at the end it makes it easier to work on the small details. Usually I work with a canvas 2 or 3 times larger than the published size.
Maybe you could try working with a shorter canvas like 1600x3200 px. Also if you use a lot of layers it can have an impact in performance. Another alternative could be trying another software, I haven't used Medibang so I don't know how better or worse it is compared to other programs. About dpi it doesn't matter unless you want to print your comic.