I know that I had a positive reaction to the lowest dosage, but the doc decided to move up to the highest dosage. He even told me that the only reason he wanted to put me on the higher dosage wa to see if the concept of "more is better" would work for me. but I was fine on the lower dosage. But the less you weigh the less insulin resistent you are going to be, so the less medicine you need to be on. My ultimate goal is to get to a low enough weight that I don't have to take the metformin at all. But the low carb essentially does the same thing, in that it corrects the insulin resistence as well. So, in my humble opinion, I would rather not take a bunch of pills if I can just watch what I eat and get the same results. So the lower dosage and a better diet is what I am personally aiming for. And it seems to be working for me, I have lost 16 pounds in the last 3.5 weeks.