Newer Oral Antidiabetics & SGLT2 Inhibitors

Newer Oral Antidiabetics & SGLT2 Inhibitors

1. Definition, scope & why a "newer-agent" class matters

• Diabetes mellitus is a heterogeneous group of metabolic disorders with a common endpoint of persistent hyperglycaemia arising from insufficient insulin secretion, insulin resistance, excessive hepatic glucose production, and disordered fat/protein metabolism; chronic hyperglycaemia drives retinopathy, nephropathy, neuropathy and cardiovascular disease (G&G 14e Ch.51, p.1023).
  • Diagnostic thresholds (ADA/WHO): fasting plasma glucose ≥7.0 mmol/L (126 mg/dL); 2-h post-75 g OGTT ≥11.1 mmol/L (200 mg/dL); HbA₁c ≥6.5%; or random glucose ≥11.1 mmol/L with symptoms (G&G 14e Ch.51, p.1027).
  • HbA₁c integrates glycaemia over ~3 months (RBC lifespan ~120 days); 4–6% (20–42 mmol/mol) is normal, ≥6.5% (48 mmol/mol) is diabetic (R&D 10e Ch.31, footnote 6, p.53–54).
• The "newer antidiabetics" are the post-sulfonylurea/post-biguanide classes developed by exploiting three previously untapped targets: the incretin axis (GLP-1 receptor agonists, the dual GIP/GLP-1 agonist tirzepatide, DPP-4 inhibitors), renal tubular glucose reabsorption (SGLT2 inhibitors), and PPARγ (glitazones); meglitinides, α-glucosidase inhibitors and amylin analogues round out the list (KDT 8e Ch.19, p.293; R&D 10e Ch.31, p.20).
• The single most important conceptual shift these agents introduced is the move from "HbA₁c-lowering alone" to "cardiorenal outcome modification" — SGLT2 inhibitors and several GLP-1 RAs reduce major adverse cardiovascular events (MACE), heart-failure hospitalisation and progression of kidney disease independently of, and beyond, glucose lowering (G&G 14e Ch.51, pp.1040, 1042; DiPiro 12e Ch.94, pp.1218–1220).