His death on Thursday was announced by MannKind Corp, where Mann served as chairman of the Valencia, California-based company from 2001 to earlier this month.
The son of an immigrant grocer, Mann amassed his fortune through founding a string of companies. His pioneering work included development of the first rechargeable pacemaker and inhalable insulin.
He started out in aerospace, where his firms developed solar cells, semiconductors and other technologies for America's military and space programs.
In 2007, Forbes magazine estimated his fortune at $2.4 billion.
MannKind chief executive Matthew Pfeffer called Mann an inspiration who will be missed by countless patients with diabetes and other serious illnesses whose lives were improved by Mann's work.
"Our resolve is now stronger than ever to continue Al's legacy of medical innovation," Pfeffer said in a statement.