For example, safety issues related to available AHAs that may be of particular concern in older patients include gastrointestinal intolerability and contraindication in patients with renal impairment for metformin; risk of congestive heart failure and fracture with thiazolidinediones; and risk of hypoglycaemia with sulphonylureas and insulin [5]. This evidence concerns the gene INS and congestive heart failure.