Diabetes Medicines in Kidney Disease

Kidney disease changes both the clearance of diabetes medicines and the risk of hypoglycaemia, because the kidney clears insulin and gluconeogenesis falls. Glycaemic targets are relaxed as function falls, to about HbA1c 53 to 58 mmol/mol (7.0 to 7.5 percent) for most patients and higher for the frail.

HbA1c reliability. It is unreliable in anaemia, after transfusion and during erythropoiesis-stimulating therapy. Add fingerstick or sensor data.

Cardiorenal benefit. SGLT2 inhibitors, and some GLP-1 receptor agonists, protect the kidney and heart independently of glucose lowering.

Preferred. Metformin while eGFR is 30 or over, an SGLT2 inhibitor, a GLP-1 receptor agonist, linagliptin and insulin.

Use with care. Gliclazide (hepatic metabolism, lowest hypoglycaemia risk among sulphonylureas), sitagliptin with dose reduction, and pioglitazone (fluid retention).

Avoid. Glibenclamide, because active metabolites accumulate. Where glibenclamide is in use, switch to gliclazide or insulin. Avoid metformin when eGFR is under 30.

Special groups.

• Pregnancy: use insulin; metformin may continue under specialist care; avoid SGLT2 inhibitors and DPP-4 inhibitors.

• Older adults: aim for a relaxed target and avoid sulphonylureas where possible.

• Dialysis: insulin and linagliptin.

• East Africa: human insulin is often the available insulin, so adjust doses with glucose records.

• Metformin: full dose (maximum 2 g daily) at eGFR 45 to 59 with monitoring, maximum 1 g daily at 30 to 44, stop under 30.

• Gliclazide: start 40 to 80 mg once daily with breakfast, maximum 320 mg daily; use lower doses at eGFR under 30.

• Sitagliptin: 100 mg once daily at eGFR 45 or over, 50 mg at 30 to 44, 25 mg under 30.

• Linagliptin: 5 mg once daily, no adjustment.

• Dapagliflozin 10 mg once daily: start at eGFR 25 or over and continue to dialysis. Empagliflozin 10 mg once daily: start at eGFR 20 or over. Glucose lowering is weaker under 45, so add other agents if needed.

• Semaglutide, dulaglutide and liraglutide: no renal adjustment. Titrate slowly, and watch for vomiting and dehydration.

• Insulin: total requirement falls, by about 25 percent at eGFR 10 to 50 and about 50 percent under 10, and then titrate by glucose.

Monitoring. Check eGFR and potassium every 3 to 6 months, HbA1c every 3 to 6 months, and glucose more often on insulin or a sulphonylurea. Review feet and eyes.

Stop rules. Hold metformin, SGLT2 inhibitors and sulphonylureas during vomiting, diarrhoea, fever or dehydration (sick day rules), and before contrast or surgery. Stop metformin under eGFR 30. Stop a sulphonylurea after any severe hypoglycaemia.

Referral and escalation. Refer for recurrent hypoglycaemia, eGFR under 30 with poor control, euglycaemic ketoacidosis symptoms, or when dialysis starts.

Common errors. Continuing glibenclamide, keeping insulin doses unchanged as function falls, using HbA1c alone, and omitting sick day rules.