When you have got an elephant by the hind leg(,) and he is trying to run away, it's best to let him run.
I'd say it was optional, though personally I would omit it. Coordinators (conjunctions) can be used to separate all kinds of clauses, both main and subordinate. The original quote looks okay to me, since the clause within the commas could be seen as parenthetical in nature, a separate unit of information.
There's also the matter of heavy vs light punctuation to consider.
With or without the first comma, the meaning is clear and unambiguous.