Kant had an interesting reply to Descartes.

He said that the "world of objects in themselves" - i.e. numinal reality, or a reality independent of our perception - must exist in order for us to have experience at all. The reason? We know that there is a reality because something must persist between each one of our "computations" - our perceptions - in order for us to be able to order our perceptions in time.

We just don't know anything about that reality besides that it exists.

To sum up: We do live in reality at some level. How many layers we are removed from the bottom-most substrate,how many simulations-within-simulations we are in, is something we might not ever know. Kant actually said we can't ever know.