What are safe diabetic medications for a patient with type 2 diabetes and impaired renal function (GFR of 31)?

Safe Diabetic Medications for Type 2 Diabetes with GFR 31

At a GFR of 31 ml/min/1.73m², metformin must be discontinued, but you should continue or initiate an SGLT2 inhibitor (such as canagliflozin or dapagliflozin) as first-line therapy, with GLP-1 receptor agonists (dulaglutide, liraglutide, or semaglutide) as the preferred add-on agent for additional glycemic control. 1

First-Line Therapy

Metformin - DISCONTINUE

• Metformin is contraindicated at GFR <30 ml/min/1.73m² and must be stopped immediately due to increased risk of lactic acidosis 1, 2
• At GFR 30-44 ml/min/1.73m², the dose should be reduced to half the maximum recommended dose, but at GFR 31, you are at the threshold where discontinuation is safest 1
• The FDA revised metformin labeling to reflect safety only down to eGFR ≥30 ml/min/1.73m² 1

SGLT2 Inhibitors - CONTINUE OR INITIATE

• SGLT2 inhibitors should be continued even at GFR 31 ml/min/1.73m² for their cardiovascular and kidney protective benefits, despite reduced glucose-lowering efficacy 1
• The CREDENCE trial demonstrated that canagliflozin reduced the risk of kidney failure by 32% and cardiovascular events by 20% in patients with eGFR as low as 30 ml/min/1.73m² 3
• Do not initiate SGLT2 inhibitors if GFR <30 ml/min/1.73m² for glycemic control, but if already on therapy, continue as long as well-tolerated and kidney replacement therapy is not imminent 1, 2
• Dapagliflozin is specifically approved for use at 10 mg once daily with eGFR 25 to <45 ml/min/1.73m² 1
• Monitor for volume depletion, blood pressure reduction, and modest initial eGFR decline (which is hemodynamic and reversible) 1

Preferred Add-On Therapy

GLP-1 Receptor Agonists - PREFERRED SECOND AGENT

• Long-acting GLP-1 receptor agonists (dulaglutide, liraglutide, or injectable semaglutide) are the preferred add-on agents when glycemic targets are not met with SGLT2 inhibitors alone 1, 2
• These agents have demonstrated cardiovascular benefits and can be used safely down to eGFR 15 ml/min/1.73m² 1
• Dulaglutide requires no dose adjustment and can be used at 0.75-1.5 mg once weekly with eGFR >15 ml/min/1.73m² 1
• Liraglutide showed significantly greater MACE risk reduction in patients with eGFR <60 ml/min/1.73m² compared to those with higher eGFR 1
• Start with low doses and titrate slowly to minimize gastrointestinal side effects (nausea, vomiting, diarrhea occur in 15-20% of patients with moderate-to-severe CKD) 1

Alternative Add-On Options

DPP-4 Inhibitors

• Linagliptin requires no dose adjustment in renal impairment and can be added if GLP-1 receptor agonists are not tolerated or affordable 2
• Sitagliptin has been studied in dialysis patients and was effective, though it requires dose adjustment at lower GFR levels 4
• DPP-4 inhibitors are less preferred than GLP-1 receptor agonists due to lack of cardiovascular outcome benefits 1

Insulin

• Insulin is always an option at any level of kidney function, including GFR 31 ml/min/1.73m² 1
• Reduce insulin doses by 25% or more when GFR <45 ml/min/1.73m² due to decreased insulin clearance and increased hypoglycemia risk 2
• The risk of hypoglycemia increases substantially in advanced CKD due to decreased renal gluconeogenesis 2

Medications to AVOID or Use with Extreme Caution

Sulfonylureas - USE WITH CAUTION

• Glimepiride can be used but must be initiated conservatively at 1 mg daily and titrated slowly to avoid hypoglycemia 1, 5
• Glipizide should be initiated at 2.5 mg once daily with slow titration 1
• Glyburide is NOT recommended due to high hypoglycemia risk in renal impairment 1
• Sulfonylureas have higher rates of severe hypoglycemia (7.7% in one study) compared to DPP-4 inhibitors (0%) in patients with ESRD 4

Thiazolidinediones

• Pioglitazone requires no dose adjustment but causes fluid retention and is contraindicated in heart failure 1
• Use only if other options are not feasible 1

Critical Monitoring and Safety Considerations

Hypoglycemia Risk

• The risk of hypoglycemia increases substantially at GFR <45 ml/min/1.73m² due to decreased renal gluconeogenesis and reduced clearance of insulin and oral agents 2
• Continuous glucose monitoring may be beneficial when HbA1c becomes unreliable in advanced CKD 2

Medication Adjustments When Starting SGLT2 Inhibitors

• If the patient is on insulin or sulfonylureas and meeting glycemic targets, reduce or withdraw these medications when adding SGLT2 inhibitors to prevent hypoglycemia 1
• For patients at risk for hypovolemia (on diuretics), consider decreasing diuretic dose before initiating SGLT2 inhibitors 1

Comprehensive Cardiovascular Risk Management

• Initiate or continue ACE inhibitor or ARB if hypertension and albuminuria are present, with careful monitoring of potassium and creatinine 1, 2
• Statin therapy is recommended regardless of baseline lipid levels to reduce cardiovascular risk 2

Monitoring Frequency

• Monitor eGFR at least every 3-6 months when GFR is 30-44 ml/min/1.73m² 1
• Monitor vitamin B12 if metformin was used long-term before discontinuation 1