Indications for SGLT2 Inhibitors in Adults with Type 2 Diabetes
SGLT2 inhibitors are indicated as add-on therapy to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control, with priority use in patients with heart failure, chronic kidney disease, or established cardiovascular disease to reduce mortality and prevent disease progression.
Primary Glycemic Indication
Add SGLT2 inhibitors to metformin and lifestyle modifications when glycemic control is inadequate (typically HbA1c ≥7%) to reduce all-cause mortality, major adverse cardiovascular events, chronic kidney disease progression, and heart failure hospitalizations 1.
SGLT2 inhibitors reduce HbA1c by 0.6-0.8% without increasing hypoglycemia risk and induce weight loss of 2-3 kg 2, 3.
Priority Cardiovascular Indications (Irrespective of HbA1c)
Heart Failure
Use SGLT2 inhibitors in all adults with type 2 diabetes and heart failure (either reduced or preserved ejection fraction) for both glycemic management and prevention of heart failure hospitalizations, regardless of current HbA1c level 1.
This represents a Class I, Level A recommendation based on cardiovascular outcome trials demonstrating 26-29% reduction in cardiovascular death or heart failure hospitalization 1, 4.
Chronic Kidney Disease
Initiate SGLT2 inhibitors in adults with type 2 diabetes and CKD (eGFR 20-60 mL/min/1.73 m² and/or albuminuria ≥200 mg/g) for glycemic management irrespective of HbA1c, and for slowing CKD progression, reducing cardiovascular events, and preventing heart failure hospitalizations 1.
SGLT2 inhibitors reduce the composite renal outcome (sustained eGFR decline ≥50%, end-stage kidney disease, or renal death) by 44% 4.
Prioritize SGLT2 inhibitors as first-line add-on therapy in patients with CKD over other glucose-lowering agents 1.
Established Cardiovascular Disease
SGLT2 inhibitors reduce cardiovascular death in adults with type 2 diabetes and established atherosclerotic cardiovascular disease 5.
FDA-approved indication for empagliflozin specifically includes reducing cardiovascular death in adults with type 2 diabetes and established cardiovascular disease 5.
Additional Metabolic Indications
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
- Consider SGLT2 inhibitors (or GLP-1 receptor agonists) in adults with type 2 diabetes, MASLD, and overweight/obesity for glycemic management and as adjunctive therapy for weight loss 1.
Critical Renal Function Thresholds
For glycemic control: Do not initiate SGLT2 inhibitors if eGFR <45 mL/min/1.73 m² as glucose-lowering efficacy is significantly reduced 1, 4.
For cardiovascular/renal protection: SGLT2 inhibitors can be initiated if eGFR ≥25 mL/min/1.73 m² (some guidelines support ≥20 mL/min/1.73 m²) 1, 4.
Glycemic benefits decrease at eGFR <45 mL/min/1.73 m², but cardiovascular and renal protective benefits persist 1, 4.
If eGFR falls below 25 mL/min/1.73 m² during treatment, continue SGLT2 inhibitors at 10 mg daily for cardiovascular/renal protection until dialysis initiation 4.
Advanced CKD Considerations
- In adults with type 2 diabetes and advanced CKD (eGFR <30 mL/min/1.73 m²), GLP-1 receptor agonists are preferred over SGLT2 inhibitors for glycemic management due to lower hypoglycemia risk and maintained cardiovascular benefit 1.
Clinical Decision Algorithm
Step 1: Assess for Priority Indications
- Heart failure (any ejection fraction) → SGLT2 inhibitor mandatory 1
- CKD with eGFR 20-60 mL/min/1.73 m² and/or albuminuria → SGLT2 inhibitor or GLP-1 RA 1
- Established cardiovascular disease → SGLT2 inhibitor strongly recommended 1, 5
Step 2: Check eGFR
- eGFR ≥45 mL/min/1.73 m² → Initiate for glycemic control and cardiorenal protection 1, 4
- eGFR 25-44 mL/min/1.73 m² → Initiate for cardiorenal protection only (minimal glycemic benefit) 1, 4
- eGFR <25 mL/min/1.73 m² → Do not initiate; consider GLP-1 RA instead 1
Step 3: Dosing
- Standard dose: 10 mg daily for dapagliflozin, empagliflozin, or canagliflozin 100 mg daily 4, 6
- No titration required for cardiovascular/renal indications 4, 6
Important Contraindications and Precautions
Withhold SGLT2 inhibitors at least 3 days before major surgery or procedures with prolonged fasting to prevent euglycemic diabetic ketoacidosis 4.
Temporarily discontinue during acute illness with reduced oral intake, fever, vomiting, or diarrhea 4.
Monitor for genital mycotic infections (6% incidence vs 1% placebo) and urinary tract infections 1, 4, 2.
Assess volume status before initiation, especially in elderly patients (≥75 years), those on diuretics, or with low systolic blood pressure 4, 6.
Absolute contraindications: severe renal impairment (eGFR <25-30 mL/min/1.73 m² for initiation), end-stage renal disease, dialysis, type 1 diabetes, history of serious hypersensitivity 5, 7.
Common Pitfall to Avoid
Do not discontinue SGLT2 inhibitors solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 4. Continue therapy at 10 mg daily for cardiorenal protection until eGFR falls below 25 mL/min/1.73 m² or dialysis is required 4.