Should I start SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors for patients with type 1 diabetes mellitus (T1DM) and chronic kidney disease (CKD)?

SGLT2 Inhibitors in Type 1 Diabetes with CKD: Not Recommended

SGLT2 inhibitors are not currently recommended for patients with type 1 diabetes mellitus (T1DM) and chronic kidney disease (CKD), as major guidelines and consensus statements specifically address only type 2 diabetes (T2D) populations, and the increased risk of diabetic ketoacidosis in T1DM patients makes this combination particularly hazardous.

Guideline Evidence Excludes Type 1 Diabetes

The most authoritative and recent guidelines explicitly limit SGLT2 inhibitor recommendations to type 2 diabetes:

• The 2022 ADA/KDIGO Consensus Report recommends SGLT2 inhibitors with proven kidney or cardiovascular benefit for patients with T2D, CKD, and eGFR ≥20 ml/min/1.73 m², but makes no such recommendation for T1DM patients 1

• The KDIGO 2020 and 2022 guidelines issue strong recommendations (Level 1B) for SGLT2 inhibitor use in T2D and CKD, positioning them as first-line therapy regardless of glycemic control, but these recommendations do not extend to T1DM 1, 2

• The 2021 ADA Standards of Care discuss SGLT2 inhibitors only in the context of type 2 diabetes and CKD, with no mention of use in T1DM with kidney disease 1

Critical Safety Concern: Diabetic Ketoacidosis Risk

The primary reason for excluding T1DM patients from SGLT2 inhibitor use relates to ketoacidosis risk:

• SGLT2 inhibitors can enhance ketogenesis, particularly when insulin dosage is reduced, substantially increasing the risk of diabetic ketoacidosis in T1DM patients who have absolute insulin deficiency 3

• Guidelines recommend withholding SGLT2 inhibitors during prolonged fasting, surgery, or critical illness when ketosis risk is elevated—conditions that pose even greater danger in T1DM patients 1, 2

• Patients must be educated about diabetic ketoacidosis symptoms and maintain at least low-dose insulin when using SGLT2 inhibitors, but the risk-benefit calculation in T1DM remains unfavorable 1

Lack of Outcome Data in Type 1 Diabetes

The robust evidence base supporting SGLT2 inhibitors in CKD comes exclusively from T2D populations:

• The landmark trials demonstrating kidney protection (CREDENCE with canagliflozin, DAPA-CKD with dapagliflozin) enrolled only patients with type 2 diabetes or non-diabetic CKD, not T1DM 1, 2, 4, 5

• While SGLT2 inhibitors may theoretically provide similar hemodynamic benefits in T1DM (reduced glomerular hyperfiltration, blood pressure, and volume overload), clinical outcome trials in T1DM with CKD have not been conducted 3

• Research acknowledges that SGLT2 inhibitors may benefit T1DM patients as adjunct therapy to insulin, but emphasizes they are not FDA-approved for this indication and require more studies, including renal and cardiovascular outcome trials 3

Practical Clinical Algorithm

For T1DM patients with CKD, focus on proven therapies:

• Optimize insulin therapy to achieve individualized glycemic targets while minimizing hypoglycemia risk 1

• Use ACE inhibitors or ARBs for patients with hypertension and albuminuria, titrated to maximum tolerated dose 1

• Prescribe statins for cardiovascular protection (moderate intensity for primary prevention, high intensity for known ASCVD) 1

• Implement comprehensive management including blood pressure control, lipid management, and smoking cessation 1

• Refer to nephrology when eGFR <30 ml/min/1.73 m² or for complex management issues 1

Common Pitfalls to Avoid

• Do not extrapolate T2D guideline recommendations to T1DM populations—the evidence base and safety profiles differ substantially 1

• Do not assume that kidney protection mechanisms observed in T2D will translate safely to T1DM given the absolute insulin deficiency and ketoacidosis risk 3

• Do not use SGLT2 inhibitors off-label in T1DM with CKD outside of clinical trial settings until dedicated outcome studies demonstrate safety and efficacy 3