Can we prescribe Jardiance (empagliflozin) for a patient with type 1 diabetes mellitus (T1DM) and chronic kidney disease (CKD) stage 4 with significant proteinuria?

Jardiance (Empagliflozin) Should NOT Be Prescribed for This Patient

Do not prescribe Jardiance (empagliflozin) for a patient with type 1 diabetes mellitus and CKD stage 4 (eGFR 15-29 mL/min/1.73 m²) with 10 grams proteinuria. This combination presents multiple absolute and relative contraindications that make this therapy inappropriate and potentially dangerous.

Critical Contraindications

Type 1 Diabetes Exclusion

• Jardiance is explicitly NOT indicated for patients with type 1 diabetes mellitus 1
• The FDA label specifically states that empagliflozin is not recommended for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis 1
• Type 1 diabetes patients face a significantly elevated risk of euglycemic diabetic ketoacidosis (DKA) with SGLT2 inhibitors, where ketoacidosis can occur even with normal blood glucose levels 2, 1
• Fatal cases of ketoacidosis have been reported in patients taking Jardiance, particularly in those with type 1 diabetes 1
• All major cardiovascular and renal outcomes trials specifically excluded type 1 diabetes patients due to safety concerns about ketoacidosis risk 2

Severe Renal Impairment Contraindication

• The FDA label explicitly contraindicates Jardiance in severe renal impairment, end-stage renal disease, or dialysis 1
• Jardiance should not be initiated in patients with eGFR less than 45 mL/min/1.73 m² 1
• CKD stage 4 (eGFR 15-29 mL/min/1.73 m²) falls well below this threshold and represents an absolute contraindication to initiation 1
• The drug should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m² 1

Mechanistic Rationale for Avoidance

Ketoacidosis Risk in Type 1 Diabetes

• The combination of type 1 diabetes with SGLT2 inhibition creates a "perfect storm" for euglycemic ketoacidosis 2
• Factors predisposing to ketoacidosis include pancreatic insulin deficiency (inherent in type 1 diabetes), reduced caloric intake, acute illness, and insulin dose reduction 1
• In type 1 diabetes patients requiring insulin, the susceptibility to ketoacidosis is further increased during acute illness, insulin pump malfunctions, or significant reductions in insulin doses 2
• Signs and symptoms of DKA with SGLT2 inhibitors include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath, often with blood glucose levels less than 250 mg/dL 1

Reduced Efficacy at Low eGFR

• At eGFR <30 mL/min/1.73 m², the drug's mechanism of action (inhibition of renal sodium-glucose cotransporter-2) is significantly impaired, resulting in minimal glycemic benefit 3
• Glucose-lowering efficacy decreases substantially with declining renal function below 45 mL/min/1.73 m² 3

Volume Depletion and Acute Kidney Injury Risk

• Jardiance causes intravascular volume contraction and can cause renal impairment 1
• Patients with chronic renal insufficiency are at particular risk for acute kidney injury when taking SGLT2 inhibitors 1
• Before initiating Jardiance, factors that may predispose patients to acute kidney injury include hypovolemia, chronic renal insufficiency, and concomitant medications (diuretics, ACE inhibitors, ARBs) 1
• With 10 grams of proteinuria, this patient likely has significant volume dysregulation and is at extremely high risk for volume depletion 4

Alternative Treatment Options for This Patient

Insulin Optimization

• Insulin remains the cornerstone of therapy for type 1 diabetes and should be titrated conservatively to avoid hypoglycemia in the setting of reduced renal clearance 2
• Patients with decreased kidney function have increased risks for hypoglycemia due to decreased clearance of insulin and impaired kidney gluconeogenesis 4
• About one third of insulin degradation is carried out by the kidney, and impaired kidney function is associated with a prolonged half-life of insulin 4

Renin-Angiotensin System Blockade

• ACE inhibitor or ARB therapy reduces the risk of progression to ESRD in patients with established CKD (eGFR <60 mL/min/1.73 m²) and UACR ≥300 mg/g 4
• Blood pressure targets <130/80 mmHg should be considered for patients with ≥300 mg/day albuminuria 4
• This patient with 10 grams proteinuria (10,000 mg/day) requires aggressive RAS blockade if not already on maximal therapy 4

Nephrology Referral

• Consider referral to a nephrologist when eGFR <30 mL/min/1.73 m² for discussion of renal replacement therapy 4
• Consultation with a nephrologist when stage 4 CKD develops has been found to reduce cost, improve quality of care, and delay dialysis 4

Critical Clinical Pitfalls to Avoid

• Do not extrapolate cardiovascular and renal benefits seen in type 2 diabetes trials to type 1 diabetes patients, as these populations were specifically excluded from landmark trials due to safety concerns 2
• Do not assume that newer SGLT2 inhibitor data (such as EMPA-KIDNEY trial results in CKD) apply to type 1 diabetes patients, as the trial enrolled patients with type 2 diabetes or no diabetes, not type 1 diabetes 5
• Do not initiate empagliflozin in type 1 diabetes patients with any level of renal impairment without recognizing the dual concerns of reduced efficacy and markedly elevated DKA risk 2

Summary of Recommendation

This patient has two absolute contraindications to Jardiance: (1) type 1 diabetes mellitus, and (2) CKD stage 4 with eGFR <30 mL/min/1.73 m². The combination creates an unacceptably high risk of life-threatening diabetic ketoacidosis with minimal potential benefit. Focus instead on optimizing insulin therapy, maximizing RAS blockade for the massive proteinuria, and ensuring prompt nephrology consultation for advanced CKD management 4, 2, 1.