Best answer
No, not as a cold message. Instagram's Messaging API only lets a business send to people who started the conversation, and the automation replies inside that thread. There is no supported way to open a new DM to someone who has never contacted you.
What counts as starting a conversation is broader than most people expect, and this is where automation earns its place:
- They send you a DM.
- They reply to your story or mention you in one.
- They comment on your post or Reel and your automation sends a private reply.
- They tap a button in an ad or a chat link that opens the thread.
That last group is why comment automation is so common: the comment is the handshake, and the private reply is a legitimate first message in a thread the person opened.
Following you is not the requirement. A non-follower who comments can receive your private reply. A follower who has never messaged you cannot receive a cold DM. If you need to reach people who have not contacted you, that is email or SMS with their consent, not Instagram.
One practical note: once the thread exists you have a 24 hour window for free-form replies. After that Instagram expects a different message type, so design the flow to finish the useful part of the conversation early rather than counting on a reply three days later.