INS and type 2 diabetes mellitus: Early after their approval for the treatment of type 2 diabetes (T2D) in 1985, the insulin-sensitizing agents thiazolidinediones (TDZs) pioglitazone, rosiglitazone and troglitazone displayed alleged safety concerns about fluid retention, increased risk of developing heart failure (HF), ischemic heart disease, and liver toxicity -not all substantiated by later observations-, determining troglitazone and rosiglitazone withdrawal and subsequent reinstatements [1].