The first day I took metformin, I took 250 mg about an hour AFTER a meal. Big mistake! I'm now taking it in the miidle of a meal and have increased to 500 mg and it is not causing me any digestive upsets. Course, I can't see that it is doing anything. Does it take a while before it starts to work? By work, I mean make me more sensitivity to insulin and allow me to lose weight. Between the metformin, low carb, and excercise/weight lifting, surely I'll see results soon.