Insulin Sensitizers

Insulin Sensitizers

1. Definition & scope

• Insulin sensitizers are oral antidiabetic agents that 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 the presence of endogenous (or exogenous) insulin to act (G&G 14e Ch.51, pp.1035–6; KDT 8e Ch.19, pp.298–9).
• Two pharmacological classes constitute this group: 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) (G&G 14e Ch.51, pp.1035–6; KDT 8e Ch.19, pp.298–300).
• A defining shared property is that they are antihyperglycaemic ("euglycaemic"), not hypoglycaemic — used as monotherapy they essentially do not cause hypoglycaemia, because they do not provoke insulin release at normal glucose levels (KDT 8e Ch.19, p.299; G&G 14e Ch.51, p.1036).
• Both classes are ineffective in type 1 diabetes and in pancreatectomised states — endogenous insulin is required for their pharmacological activity (KDT 8e Ch.19, pp.299–300; G&G 14e Ch.51, p.1036).
  • The insulin-sensitizer label applies specifically to the biguanides and thiazolidinediones. The other oral and injectable antidiabetics — insulin secretagogues (sulfonylureas, meglitinides), incretin-based agents (DPP-4 inhibitors, GLP-1 receptor agonists), SGLT-2 inhibitors, α-glucosidase inhibitors and exogenous insulin — act by mechanisms other than direct insulin sensitisation, and are considered here only where they bear on combination therapy.