SGLT2 Inhibitor Prescribing

Sodium glucose cotransporter 2 inhibitors block renal glucose reabsorption, causing glycosuria, mild osmotic diuresis and natriuresis. Beyond glucose lowering, they reduce heart failure hospitalisation and slow chronic kidney disease progression, so they are chosen for organ protection even when glucose is already controlled.

Glucose effect falls with eGFR. Glycaemic benefit is small under eGFR 45, but cardiorenal benefit continues.

Haemodynamic dip. A small early fall in eGFR of up to 30% is expected and is not a reason to stop.

Indications. Type 2 diabetes with atherosclerotic cardiovascular disease, heart failure (reduced or preserved ejection fraction), or chronic kidney disease. Empagliflozin and dapagliflozin are also used for heart failure and chronic kidney disease without diabetes.

Contraindications. Type 1 diabetes (not licensed), history of diabetic ketoacidosis, pregnancy and breastfeeding, recurrent severe genitourinary infection, and eGFR under the label limit.

Use with caution. Elderly or frail patients, patients on loop diuretics, low body mass index with poor intake, heavy alcohol use, very low carbohydrate diets, and patients with pancreatic insufficiency.

Doses. - Empagliflozin 10 mg orally once daily; 25 mg for added glucose lowering when eGFR is 45 or more. - Dapagliflozin 10 mg orally once daily. - Canagliflozin 100 mg orally once daily, increased to 300 mg if eGFR is 60 or more.

Kidney limits. Empagliflozin and dapagliflozin can be started at eGFR 20 and continued until dialysis. For glycaemia alone, avoid starting under eGFR 45.

Hepatic impairment. Empagliflozin needs no adjustment. Dapagliflozin is started at 5 mg in severe impairment where permitted.

Combination therapy. - With insulin or a sulphonylurea: reduce the insulin or sulphonylurea dose by 10 to 20% at the start to limit hypoglycaemia. - With a loop diuretic: consider reducing the diuretic dose if the patient is euvolaemic, and monitor for volume depletion.

Perioperative and sick-day rule. Withhold during acute illness, vomiting, reduced intake or fasting. Stop 3 days before elective surgery (ertugliflozin 4 days), and restart when eating and drinking normally.

Special groups. - Pregnancy: avoid; stop before conception. - Breastfeeding: not advised. - Older adults: start with attention to volume status and falls. - Children: dapagliflozin and empagliflozin are licensed for type 2 diabetes from 10 years in some regions.

Monitoring. eGFR and blood pressure at 2 to 4 weeks, then every 3 to 6 months. Ketones in any patient who is unwell with nausea, vomiting or abdominal pain, even with normal glucose.

Adverse effects. Genital mycotic infections, urinary tract infections, volume depletion and hypotension, euglycaemic diabetic ketoacidosis, Fournier gangrene (rare), and lower limb amputation risk with canagliflozin.

Stopping. Stop for ketoacidosis, Fournier gangrene, recurrent severe genital infection, or persistent volume depletion with falling eGFR.

Referral and escalation. Treat suspected ketoacidosis as an emergency: give fluids and intravenous insulin with glucose, and stop the drug. Blood ketones of 3.0 mmol/L or more with acidosis confirm diabetic ketoacidosis.