Insulin Sensitizers

Introduction & classification

• Insulin sensitizers lower blood glucose by improving the responsiveness of target tissues (liver, skeletal muscle, adipose) to insulin, rather than by stimulating insulin secretion from pancreatic β cells; they require endogenous (or exogenous) insulin to act.
• Two classes — the biguanide metformin (an AMPK activator acting chiefly on the liver) and the thiazolidinediones (TZDs / "glitazones") — pioglitazone and rosiglitazone (nuclear PPARγ agonists acting chiefly on adipose tissue).
• Euglycaemic, not hypoglycaemic — as monotherapy they are antihyperglycaemic and essentially do not cause hypoglycaemia, because they do not provoke insulin release at normal glucose levels.
• Type 1 DM — both classes are ineffective in type 1 diabetes and pancreatectomised states — endogenous insulin is required for activity.
• Biguanides — metformin is the only biguanide in clinical use; the congeners phenformin and buformin were withdrawn in the 1970s (phenformin banned in India since 2003) for an unacceptable rate of lactic acidosis.
• Thiazolidinediones — pioglitazone is the only TZD marketed in India; rosiglitazone (available in some countries) is banned in India since 2010; troglitazone was withdrawn in 2000 for idiosyncratic hepatotoxicity.