SGLT2 Inhibitors in Type 1 Diabetes with Renal Impairment
SGLT2 inhibitors are NOT recommended for your patient with type 1 diabetes, despite the renal impairment and ACE/ARB intolerance. While these agents show promise in type 2 diabetes with CKD, they remain contraindicated or not approved for routine use in type 1 diabetes due to unacceptable diabetic ketoacidosis (DKA) risk. 1
Why SGLT2 Inhibitors Are Not Appropriate Here
Lack of Approval for Type 1 Diabetes
SGLT2 inhibitors have insufficient data to recommend clinical use in type 1 diabetes at this time. 1 The FDA has not approved these agents for type 1 diabetes despite temporary European approval that was subsequently withdrawn. 2
The European Medical Agency (EMA) temporarily licensed dapagliflozin and sotagliflozin for type 1 diabetes but withdrew this recommendation due to safety concerns, primarily the increased risk of diabetic ketoacidosis. 2
Unacceptable DKA Risk in Type 1 Diabetes
SGLT2 inhibitors significantly increase the risk of diabetic ketoacidosis in type 1 diabetes patients, including euglycemic DKA (ketoacidosis with only mild-to-moderate glucose elevations). 3, 2 This is a life-threatening adverse event that occurs more frequently in type 1 diabetes than the background rate seen in type 2 diabetes. 2
The FDA Endocrinologic and Metabolic Drugs Advisory Committee was divided on approval, specifically citing concerns about DKA risk in type 1 diabetes. 2
The ACE/ARB Intolerance Issue
Heartburn Is NOT a Contraindication to ACE/ARB Rechallenge
Severe heartburn is not a recognized adverse effect of ACE inhibitors or ARBs. 4 The known adverse effects include hyperkalemia, acute increases in serum creatinine, cough (ACE inhibitors), and angioedema—but not gastrointestinal symptoms like heartburn. 1
You should rechallenge with an ACE inhibitor or ARB, as the previous heartburn was likely coincidental or related to another cause. 5, 6 These agents remain the cornerstone of renoprotection in diabetic kidney disease for both type 1 and type 2 diabetes. 1
Evidence-Based Approach to Renoprotection in Type 1 Diabetes
Step 1: Initiate ACE Inhibitor or ARB
Either ACE inhibitors or ARBs are recommended for type 1 diabetes patients with hypertension and macroalbuminuria (≥300 mg/24h). 1 ARBs can be used as an alternative if ACE inhibitors cannot be used. 1
Start with lisinopril 10 mg daily or enalapril 5 mg daily, titrating to maximum approved doses (lisinopril 20-40 mg daily, enalapril 10-40 mg daily). 6, 7
Monitor serum creatinine and potassium within 2-4 weeks of initiation. 1 Accept up to 30% increase in serum creatinine—this reflects hemodynamic changes and is expected, not a reason to discontinue. 1, 6
Step 2: Add Diuretic if Needed
- Diuretics potentiate the beneficial effects of ACE inhibitors and ARBs in hypertensive patients with diabetic kidney disease. 1 Between 60-90% of patients in major trials required thiazide-type or loop diuretics in addition to RAS blockade. 1
Step 3: Optimize Glycemic Control
Continue intensive insulin therapy with multiple daily injections or continuous subcutaneous insulin infusion. 1
Metformin can be considered if eGFR ≥30 mL/min/1.73 m², with dose reduction to 1000 mg daily if eGFR is 30-44 mL/min/1.73 m². 1
Critical Pitfalls to Avoid
Never combine an ACE inhibitor with an ARB—dual RAS blockade increases adverse events including acute kidney injury and hyperkalemia without additional benefit. 1, 6, 7
Do not discontinue ACE inhibitor/ARB for mild-to-moderate increases in serum creatinine (<30%) in the absence of volume depletion. 1
Do not use SGLT2 inhibitors off-label in type 1 diabetes given the withdrawn regulatory approval and DKA risk. 2
When to Refer to Nephrology
Refer to a nephrologist if: