I found it quite difficult to get GPGME working with Mutt in OS X, I was using Homebrew to install mutt. I could see the option in the brew build file to use GPGME, but it was set as an optional dependency. I fought with it for a while then jumped across to #homebrew on freenode to get an answer.
I had to force brew to build mutt from source to get the dependency included. You will have to uninstall mutt if you have already installed it.
brew install mutt --build-from-source --with-gpgme
You will need to add the correct bits to your .muttrc to get mutt to use.
set crypt_use_gpgme = yes set crypt_autosign = yes set pgp_sign_as = 0xYOURGPGKEYGOESHERE*****