I am going through my second adjustment period on the metformin (glucophage). I came off of my metformin to isolate the cause of some unpleasant symptoms only to find out that it wasn't the metformin, so I am going back on it now (500 XR mg AM/PM). It takes me three weeks to adjust to the nausea and sometimes overwhelming fatigue. This time however I was looking for others who felt depressed or blue while on the metformin and I am glad to discover I am not the only one. I can say that it helps a lot to use the natural Trivita products (www.Trivita.com). Metformin reduces (a lot) the absorption of B vitamins, which help the body in a lot of ways- moods being one of them. I ordered the sublingual B-12 complex and Energy Now products and they are helping me get through the acclimation period again. I am on the Metformin for PCOS and hormone imbalance. Depression and anxiety are sadly something I am prone to and have to reallly battle with. The nausea and fatigue doesn't help those, but I assure you after 3 weeks things get a lot easier as far as the nausea and fatigue are concerned.