Antidiabetics

Mechanisms

Antidiabetic agents act through diverse mechanisms - insulin (direct hormone replacement), metformin (reduced hepatic gluconeogenesis, improved peripheral insulin sensitivity), sulfonylureas (stimulated pancreatic insulin secretion), SGLT2 inhibitors (renal glucose excretion), and GLP-1 receptor agonists (incretin-mediated insulin secretion, appetite suppression, delayed gastric emptying) - mechanism determines hypoglycaemia risk, cardiovascular/renal benefit profile, and appropriate patient selection

Amongst the most widely prescribed medication classes globally given the high and rising prevalence of type 2 diabetes

SGLT2 inhibitors and GLP-1 receptor agonists have demonstrated cardiovascular and renal outcome benefits independent of glycaemic control alone in trial evidence, explaining their elevated position in current type 2 diabetes treatment algorithms particularly in patients with established cardiovascular or renal disease
Sulfonylureas and insulin carry genuine hypoglycaemia risk (insulin-independent glucose-lowering agents like metformin and SGLT2 inhibitors carry minimal hypoglycaemia risk as monotherapy) - this mechanism-based risk difference should inform agent selection, particularly in older or frail patients

Renal function assessment is relevant to several classes - metformin dose adjustment/contraindication at significant renal impairment (though thresholds have been liberalised from older, more conservative cut-offs), SGLT2 inhibitor efficacy declining at very low eGFR though renoprotective benefit can persist
Volume status assessment before SGLT2 inhibitor initiation given osmotic diuresis effect and euglycaemic ketoacidosis risk in specific clinical scenarios (prolonged fasting, acute illness, perioperative)

SGLT2 inhibitors and GLP-1 receptor agonists are now favoured early in type 2 diabetes management, particularly with cardiovascular/renal disease, reflecting their outcome benefit beyond glycaemic control
Sick day management (temporarily withholding SGLT2 inhibitors and metformin during acute illness/reduced oral intake) reduces euglycaemic DKA and lactic acidosis risk respectively

SGLT2 inhibitor-associated euglycaemic ketoacidosis (a specific, easily missed presentation given near-normal glucose), metformin-associated lactic acidosis risk in renal impairment, sulfonylurea/insulin hypoglycaemia risk, sick day medication rules
SGLT2 inhibitors can cause euglycaemic diabetic ketoacidosis - a presentation where blood glucose is only mildly elevated or even normal despite significant ketoacidosis, meaning a near-normal glucose should not be used to reassure against DKA in a patient on this drug class who is unwell, particularly during acute illness, fasting, or the perioperative period

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