Red Flags
- Severe hypoglycaemia in diabetes with CKD G4–G5 — review insulin and sulfonylurea dose; switch where possible to lower-risk agents (SGLT2 inhibitor, GLP-1 RA, DPP-4 inhibitor)[1]
- Diabetic ketoacidosis on SGLT2 inhibitor (often euglycaemic) — stop drug, IV fluid + insulin; admit; do not restart without specialist review[1]
- Persistent hyperkalaemia >5.5 mmol/L on RAS inhibitor + finerenone — review concurrent agents, dietary potassium, and use potassium binders before withdrawal[1]
- AKI on SGLT2 inhibitor with intercurrent illness — pause drug per sick-day rules; investigate volume status; restart after recovery[1]
First-line treatment
Interventions
- Comprehensive cardio-renal pillar therapy[1]All adults with T2DM + CKD: ACEi/ARB + SGLT2 inhibitor + statin + lifestyle change. Add GLP-1 RA for glycaemic and weight benefit; finerenone for residual albuminuria despite RAS + SGLT2
- Individualised HbA1c target 6.5–8.0%[1]Tighter target for younger, low hypoglycaemia risk, no advanced CKD; relax to 7.5–8.0% in elderly, frail, advanced CKD G4–G5, dialysis, or recurrent hypoglycaemia
- Lifestyle and dietary optimisation[1]Dietary protein 0.8 g/kg/day in CKD G3–G5 (not on dialysis); sodium <2 g/day; aerobic + resistance exercise; smoking cessation; weight reduction in obesity
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Metformin[1] | Biguanide | 500 mg PO BD; titrate to 2000 mg/day; reduce dose at eGFR 30–45; stop if eGFR <30 | Children ≥10 years: 500 mg BD up to 2000 mg/day | First-line for type 2 diabetes; review at every CKD stage transition; lactic acidosis risk with intercurrent illness — sick-day rules |
| SGLT2 inhibitor (dapagliflozin, empagliflozin, canagliflozin)[1] | Sodium-glucose cotransporter 2 inhibitor | Dapagliflozin 10 mg PO daily; empagliflozin 10 mg PO daily; canagliflozin 100 mg PO daily | — | Recommend in T2DM + CKD with eGFR ≥20 regardless of HbA1c; expected eGFR dip on initiation; sick-day rules; risk of euglycaemic DKA, genitourinary mycotic infection |
| GLP-1 receptor agonist (semaglutide, liraglutide, dulaglutide)[1] | Glucagon-like peptide-1 receptor agonist | Semaglutide 0.25 mg SC weekly start, titrate to 1 mg; liraglutide 0.6 mg SC daily start, titrate to 1.8 mg; dulaglutide 0.75–1.5 mg SC weekly | — | Add when additional glycaemic control or weight loss needed; cardiovascular and renal benefit; pause before elective surgery per local protocol; nausea on initiation |
| Finerenone[1] | Non-steroidal mineralocorticoid receptor antagonist | 10–20 mg PO once daily by eGFR and potassium; titrate every 4 weeks | — | T2DM + CKD with persistent UACR ≥30 mg/g despite optimal RAS inhibitor + SGLT2 inhibitor; avoid eGFR <25 or K >5.0; FIDELIO-DKD/FIGARO-DKD trials |
| DPP-4 inhibitor (linagliptin)[1] | Dipeptidyl peptidase-4 inhibitor | Linagliptin 5 mg PO daily — no dose adjustment in CKD | — | Add-on glycaemic agent in CKD with low hypoglycaemia risk; avoid saxagliptin (HF risk in CKD) |
| Insulin (basal ± rapid)[1] | Insulin therapy | Basal insulin (glargine, degludec) 0.1–0.2 U/kg/day start; rapid analogue at meals 0.05 U/kg per meal; reduce dose 25–50% in CKD G4–G5 or dialysis | Per paediatric endocrinology | Required when oral therapy insufficient or contraindicated; CKD reduces insulin clearance — increased hypoglycaemia risk |
Metformin[1]
Biguanide
- Adult
- 500 mg PO BD; titrate to 2000 mg/day; reduce dose at eGFR 30–45; stop if eGFR <30
- Paediatric
- Children ≥10 years: 500 mg BD up to 2000 mg/day
First-line for type 2 diabetes; review at every CKD stage transition; lactic acidosis risk with intercurrent illness — sick-day rules
SGLT2 inhibitor (dapagliflozin, empagliflozin, canagliflozin)[1]
Sodium-glucose cotransporter 2 inhibitor
- Adult
- Dapagliflozin 10 mg PO daily; empagliflozin 10 mg PO daily; canagliflozin 100 mg PO daily
- Paediatric
- —
Recommend in T2DM + CKD with eGFR ≥20 regardless of HbA1c; expected eGFR dip on initiation; sick-day rules; risk of euglycaemic DKA, genitourinary mycotic infection
GLP-1 receptor agonist (semaglutide, liraglutide, dulaglutide)[1]
Glucagon-like peptide-1 receptor agonist
- Adult
- Semaglutide 0.25 mg SC weekly start, titrate to 1 mg; liraglutide 0.6 mg SC daily start, titrate to 1.8 mg; dulaglutide 0.75–1.5 mg SC weekly
- Paediatric
- —
Add when additional glycaemic control or weight loss needed; cardiovascular and renal benefit; pause before elective surgery per local protocol; nausea on initiation
Finerenone[1]
Non-steroidal mineralocorticoid receptor antagonist
- Adult
- 10–20 mg PO once daily by eGFR and potassium; titrate every 4 weeks
- Paediatric
- —
T2DM + CKD with persistent UACR ≥30 mg/g despite optimal RAS inhibitor + SGLT2 inhibitor; avoid eGFR <25 or K >5.0; FIDELIO-DKD/FIGARO-DKD trials
DPP-4 inhibitor (linagliptin)[1]
Dipeptidyl peptidase-4 inhibitor
- Adult
- Linagliptin 5 mg PO daily — no dose adjustment in CKD
- Paediatric
- —
Add-on glycaemic agent in CKD with low hypoglycaemia risk; avoid saxagliptin (HF risk in CKD)
Insulin (basal ± rapid)[1]
Insulin therapy
- Adult
- Basal insulin (glargine, degludec) 0.1–0.2 U/kg/day start; rapid analogue at meals 0.05 U/kg per meal; reduce dose 25–50% in CKD G4–G5 or dialysis
- Paediatric
- Per paediatric endocrinology
Required when oral therapy insufficient or contraindicated; CKD reduces insulin clearance — increased hypoglycaemia risk
Safety-net
- Sick-day rules — temporarily hold metformin, SGLT2 inhibitor, ACE inhibitor/ARB, finerenone, and reduce insulin during dehydrating illness; restart when eating and drinking normally[1]
- Watch for euglycaemic DKA on SGLT2 inhibitor — nausea, abdominal pain, breathlessness with normal blood glucose; check ketones and seek same-day review[1]
- Carry rapid-acting glucose; teach household members glucagon use if on insulin or sulfonylurea — hypoglycaemia recognition is harder in advanced CKD[1]
Referral criteria
- T2DM + CKD with persistent UACR ≥30 mg/g despite optimal RAS + SGLT2 inhibitorNephrology and consider finerenone[1]
- Recurrent severe hypoglycaemia in CKD on insulin or sulfonylureaDiabetes specialist for therapy switch and continuous glucose monitoring[1]
- eGFR <30 or rapid eGFR decline (>5 mL/min/year)Nephrology[1]
- Pregnancy in T2DM with CKDJoint diabetes, obstetric, and nephrology clinic[1]
Clinical summary
Glycaemic and cardio-renal protective therapy for adults with type 2 diabetes and CKD; SGLT2 inhibitor + GLP-1 RA + finerenone framework.