What medications can a patient with type 2 diabetes (T2D) and impaired renal function take to control blood glucose levels?

Medications for Diabetic Patients with Kidney Failure

For a diabetic patient with kidney failure, SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) should be the first-line therapy if eGFR ≥20 mL/min/1.73 m², combined with metformin if eGFR ≥30 mL/min/1.73 m², followed by long-acting GLP-1 receptor agonists (dulaglutide, liraglutide, or semaglutide) if additional glucose control is needed. 1, 2, 3

Treatment Algorithm Based on Kidney Function

eGFR ≥30 mL/min/1.73 m²

First-line combination therapy:

• SGLT2 inhibitor (empagliflozin 10-25 mg daily, canagliflozin 100 mg daily, or dapagliflozin 10 mg daily) 1
• Metformin at full dose if eGFR ≥60 mL/min/1.73 m²; reduce to half dose (maximum 1000 mg daily) if eGFR 30-44 mL/min/1.73 m² 1, 3

If glycemic targets not met, add:

• Long-acting GLP-1 receptor agonist (preferred): dulaglutide 0.75-1.5 mg weekly, liraglutide 1.2-1.8 mg daily, or semaglutide 0.5-1 mg weekly 1, 2
• These agents require no dose adjustment and provide cardiovascular benefits 1

eGFR 20-29 mL/min/1.73 m²

Critical change: Stop metformin immediately due to lactic acidosis risk 1, 3

Continue or initiate:

• SGLT2 inhibitor (continue for cardiovascular and kidney protection despite reduced glucose-lowering effect) 1, 2, 3
• GLP-1 receptor agonist if additional glucose control needed (dulaglutide can be used down to eGFR >15 mL/min/1.73 m²) 1

Alternative options if above not tolerated:

• Linagliptin (DPP-4 inhibitor requiring no dose adjustment) 3
• Insulin (always an option but requires 25% or more dose reduction and careful hypoglycemia monitoring) 2, 3

eGFR <20 mL/min/1.73 m² or on Dialysis

Primary therapy:

• Insulin becomes the mainstay, with careful dose reduction (25% or more) and frequent monitoring due to markedly increased hypoglycemia risk 2, 4
• GLP-1 receptor agonists maintain glucose-lowering efficacy (dulaglutide can be used with eGFR >15 mL/min/1.73 m²) 1

Continue SGLT2 inhibitor if already on therapy and well-tolerated, for cardiovascular and kidney protection until dialysis or transplantation 2

Medications to AVOID in Kidney Failure

Absolutely contraindicated:

• Metformin when eGFR <30 mL/min/1.73 m² (lactic acidosis risk) 1, 3
• Glyburide at any level of kidney impairment (severe hypoglycemia risk) 3
• First-generation sulfonylureas (chlorpropamide, tolazamide, tolbutamide) 2

Use with extreme caution or avoid:

• Most sulfonylureas increase hypoglycemia risk substantially in CKD; if necessary, use only glipizide (no active metabolites) at 1 mg starting dose 2, 5
• Pioglitazone causes fluid retention and is contraindicated in heart failure 3
• Exenatide (GLP-1 RA) not recommended when eGFR <45 mL/min/1.73 m² 1, 3

Critical Safety Considerations

Hypoglycemia risk increases dramatically when eGFR <45 mL/min/1.73 m² due to:

• Decreased renal gluconeogenesis 2
• Reduced clearance of insulin and oral agents 2
• Impaired recognition of hypoglycemia symptoms in elderly patients 5

When initiating SGLT2 inhibitors or GLP-1 receptor agonists:

• Reduce or withdraw insulin/sulfonylurea doses by 25-50% if patient is already meeting glycemic targets 2, 3
• Assess volume depletion risk, especially with concurrent diuretic use; consider reducing diuretic dose 2
• Monitor for genital infections and educate about diabetic ketoacidosis risk (particularly during illness or perioperative periods) 2

Monitor eGFR every 3-6 months when eGFR is 30-60 mL/min/1.73 m², and more frequently when <30 mL/min/1.73 m² 1, 3

Monitor vitamin B12 if metformin was used long-term (>4 years) before discontinuation 1, 3

Why SGLT2 Inhibitors Are First-Line Despite Kidney Failure

The cardiovascular and kidney protective benefits of SGLT2 inhibitors persist even when glucose-lowering efficacy diminishes at lower eGFR levels 1, 2. The CREDENCE trial demonstrated that canagliflozin reduced the relative risk of the primary renal outcome (end-stage renal disease, doubling of serum creatinine, or renal/CV death) by 30% in patients with eGFR 30-90 mL/min/1.73 m² 1. These benefits include reduced heart failure hospitalizations, slowed GFR decline, and reduced albuminuria 1, 2.

Additional Essential Management

Initiate or continue ACE inhibitor or ARB if hypertension and albuminuria are present, targeting systolic blood pressure to 130 mmHg but not <120 mmHg 1

Statin therapy is mandatory regardless of baseline lipid levels to reduce cardiovascular risk 2

HbA1c becomes less reliable in advanced CKD; consider continuous glucose monitoring for more accurate assessment 3