What is the risk of acute kidney injury (AKI) in an older adult with type 2 diabetes mellitus (T2DM) and heart failure with preserved ejection fraction (HFpEF) when initiating a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, glucagon-like peptide-1 (GLP-1) receptor agonist, or dipeptidyl peptidase-4 (DPP-4) inhibitor?

SGLT-2 Inhibitors and Risk of Acute Kidney Injury in Older Adults with T2DM and HFpEF

The risk of acute kidney injury (AKI) is lower with the initiation of an SGLT-2 inhibitor than with a GLP-1 receptor agonist or a DPP-4 inhibitor in older adults with type 2 diabetes mellitus. This finding from the Medicare population-based cohort study by Zhou and colleagues directly applies to your 70-year-old patient with newly diagnosed T2DM and HFpEF.

Evidence on SGLT-2 Inhibitors and AKI Risk

Reduced AKI Risk with SGLT-2 Inhibitors

• SGLT-2 inhibitors have been shown to have a lower risk of AKI compared to DPP-4 inhibitors and GLP-1 receptor agonists in older adults with T2DM 1

• In a large Medicare study of adults aged 66+ years, SGLT-2 inhibitor initiation was associated with:

  • 29% lower risk of AKI compared to DPP-4 inhibitors (HR 0.71,95% CI 0.65-0.76)
  • 19% lower risk of AKI compared to GLP-1 receptor agonists (HR 0.81,95% CI 0.75-0.87)

• Another propensity-matched analysis found that SGLT-2 inhibitor users had 60% lower hazards of AKI compared to non-users (adjusted HR 0.4,95% CI 0.2-0.7) 2

SGLT-2 Inhibitors in Heart Failure with Preserved Ejection Fraction

SGLT-2 inhibitors are specifically recommended for patients with HFpEF:

• The American Heart Association and Heart Failure Society of America guideline specifically recommends SGLT-2 inhibitors for patients with HFpEF, as shown in their case examples 3
• For patients with T2DM and HFpEF (EF 60%), SGLT-2 inhibitors are listed as a preferred option that "may decrease risk of HF hospitalization" 3
• SGLT-2 inhibitors are effective across the entire spectrum of heart failure, regardless of ejection fraction 4

Clinical Decision Algorithm for Your Patient

1. First-line recommendation: Initiate an SGLT-2 inhibitor

   • Benefits: Reduces risk of HF hospitalization, cardiovascular events, and progression of chronic kidney disease 3
   • Lower risk of AKI compared to other newer diabetes medications 1
   • Specifically recommended for patients with HFpEF 3

2. Safety considerations when initiating SGLT-2 inhibitor:

   • Evaluate renal function prior to initiation 5
   • Monitor for potential volume depletion, especially if patient is on diuretics
   • Consider reducing dose of any sulfonylureas by 50% if patient is taking them 6
   • Schedule follow-up within 30 days to assess tolerance and adjust medications 6

3. Patient education points:

   • Explain the benefits for both diabetes and heart failure
   • Advise about potential genital mycotic infections and importance of hygiene 5
   • Instruct on signs of volume depletion to monitor for

Common Pitfalls to Avoid

1. Misinterpreting FDA warnings: While FDA labels include warnings about AKI with SGLT-2 inhibitors 5, real-world evidence shows they actually have a lower risk compared to other newer diabetes medications 1, 2

2. Withholding beneficial therapy: Avoiding SGLT-2 inhibitors due to concerns about AKI may deprive patients of significant cardiovascular and renal benefits

3. Failing to adjust concomitant medications: When starting an SGLT-2 inhibitor, consider reducing doses of diuretics or sulfonylureas to prevent hypotension or hypoglycemia 6

4. Overlooking temporary discontinuation scenarios: Consider temporarily discontinuing SGLT-2 inhibitors during acute illness, prolonged fasting, or surgical procedures to reduce risk of ketoacidosis or AKI 5

SGLT-2 inhibitors are the preferred choice for this patient with T2DM and HFpEF, with evidence showing they have a lower risk of AKI compared to other newer diabetes medications, contrary to the resident's concerns.