“You look tired!”
You may be trying to be sympathetic, but pointing out that someone looks tired is just another way of saying “Wow, you look like crap!” Nobody wants to hear it, and saying it just makes you sound insensitive (and even flat-out rude). The same goes for “Did you lose weight?” Even if it’s the truth, you’re basically pointing out to the person that you noticed how fat they used to be. Bad idea! In both cases, a sincere “How are you?” is better. Someone who’s legitimately tired can talk about the new baby or puppy that’s keeping them up all night, if they want to; someone who’s lost weight can say “I feel great since I lost 20 pounds!” Either way, you’re letting the person you’re speaking with direct the conversation, so you’re less likely to step on their toes.