What SGLT2 (sodium-glucose linked transporter 2) inhibitors are not included in American Diabetes Association (ADA) recommendations for key treatment in reducing cardiovascular disease and heart failure?

SGLT2 Inhibitors Not Included in ADA Recommendations for Cardiovascular Disease and Heart Failure Reduction

Sotagliflozin and ipragliflozin are the SGLT2 inhibitors not included in the American Diabetes Association (ADA) recommendations for key treatment in reducing cardiovascular disease and heart failure. 1

Current ADA-Recommended SGLT2 Inhibitors

According to the 2025 ADA Standards of Care, the following SGLT2 inhibitors are specifically recommended for cardiovascular disease and heart failure risk reduction:

• Empagliflozin
• Canagliflozin
• Dapagliflozin
• Ertugliflozin (with lesser benefits noted) 1

These recommendations are based on large randomized controlled trials that demonstrated statistically significant reductions in cardiovascular events for these FDA-approved SGLT2 inhibitors.

Evidence Supporting ADA-Recommended SGLT2 Inhibitors

Cardiovascular Outcomes Trials

The ADA recommendations are based on several key trials:

• Empagliflozin: EMPA-REG OUTCOME trial showed significant reduction in 3-point MACE (major adverse cardiovascular events) 1
• Canagliflozin: CANVAS program and CREDENCE trial demonstrated significant reduction in 3-point MACE 1
• Dapagliflozin: DECLARE-TIMI 58 showed significant reduction in the combined endpoint of heart failure hospitalization or CV death 1
• Ertugliflozin: Included in recommendations but with "lesser benefits" noted compared to other agents 1

All of these agents have consistently shown reduction in heart failure hospitalization across various patient populations 2.

SGLT2 Inhibitors Not Included in ADA Recommendations

Sotagliflozin

Sotagliflozin is a dual SGLT1/SGLT2 inhibitor that has shown cardiovascular benefits in clinical trials:

• The SOLOIST-WHF trial demonstrated a 33% reduction in the combined endpoint of cardiovascular death, HF hospitalization, or urgent HF visits 1
• However, as of the 2025 ADA Standards of Care, sotagliflozin is not included in their key recommendations for cardiovascular disease and heart failure risk reduction 1
• A network meta-analysis suggested sotagliflozin may have the highest probability of reducing composite CV death/HF hospitalization (97.6%) in heart failure-specific trials 3

Ipragliflozin

Ipragliflozin is another SGLT2 inhibitor that is not included in the ADA recommendations for cardiovascular disease and heart failure risk reduction 1.

Clinical Implications

When selecting an SGLT2 inhibitor for cardiovascular risk reduction:

1. First-line options: Choose from the ADA-recommended agents (empagliflozin, canagliflozin, dapagliflozin, or ertugliflozin) 1

2. Patient-specific considerations:

   • For patients with established atherosclerotic cardiovascular disease, all recommended SGLT2 inhibitors reduce risk of major adverse cardiovascular events 1
   • For heart failure reduction, the evidence is strongest across all patient populations, including those with and without diabetes 2
   • For renal protection, all recommended SGLT2 inhibitors show benefit 1

3. Safety considerations:

   • Monitor for genital infections, which are more common with SGLT2 inhibitors 1
   • Be cautious with canagliflozin in patients with history of amputation or severe peripheral vascular disease 1
   • Adjust diuretics if needed to prevent volume depletion 1

Conclusion

When selecting an SGLT2 inhibitor specifically for cardiovascular disease and heart failure risk reduction, clinicians should prioritize the ADA-recommended agents (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin). Sotagliflozin and ipragliflozin, while showing some promise in research, are not currently included in the ADA recommendations for this specific indication.