Metformin suppresses adipogenesis through both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms
Clinical evidence suggests that bone health is affected in some patients with type 2 diabetes mellitus (T2DM). T2DM is associated with an increased incidence of bone fractures. Although factors associated with T2DM, such as an increased risk of falls, may be in part responsible for the higher risk of fracture, decreased bone quality may also play an important role. In addition, treatment with thiazolidinediones (TZDs), a class of antidiabetic drugs, causes bone loss and further increases fracture risk. In vitro and in vivo animal studies have demonstrated that TZD-mediated PPARgamma activation increases bone resorption and reduces the formation of new bone. Aging and estrogen deficiency are sensitizing factors to bone loss as a result of TZD therapy. Biguanides and sulfonylureas do not appear to have adverse effects on bone, whereas insulin increases the incidence of fractures, although the underlying mechanism responsible for this increase is unknown. Preclinical evidence suggests that incretin-based drugs may be beneficial for bone, but clinical evidence to support this hypothesis is not yet available. In summary, bone is a target of certain antidiabetic therapies and, therefore, caution is necessary in the choice of treatment for patients who are at risk of skeletal complications.