Do sodium-glucose co-transporter-2 (SGLT-2) inhibitors improve diastolic dysfunction?

SGLT-2 Inhibitors and Diastolic Dysfunction

SGLT-2 inhibitors improve diastolic dysfunction in patients with type 2 diabetes and heart failure, with the strongest evidence supporting their use in HFrEF (EF ≤40%), though emerging data suggest benefits may extend to preserved ejection fraction and even non-heart failure populations.

Guideline-Based Recommendations

The 2022 AHA/ACC/HFSA guidelines establish SGLT-2 inhibitors as first-line agents for hyperglycemia management in diabetic patients with heart failure or at high risk for heart failure 1. The Canadian guidelines provide more specific direction: SGLT-2 inhibitors like dapagliflozin should be used in patients with mild to moderate HFrEF (EF ≤40%) with or without diabetes to improve symptoms, quality of life, and reduce hospitalization and cardiovascular mortality 2.

These guideline recommendations are based on landmark trials (DAPA-HF, EMPEROR-Reduced) showing 26% reduction in heart failure hospitalization and 14% reduction in cardiovascular death 1. Importantly, benefits were consistent regardless of diabetes status.

Evidence for Diastolic Function Improvement

Strongest Recent Evidence

The most compelling recent data comes from a 2026 real-world study in hypertrophic cardiomyopathy patients, which demonstrated significant improvements in diastolic parameters after 6 months of SGLT-2i therapy 3:

• E/e' ratio improved by -5.1 (vs. +0.4 in controls, p<0.001)
• Septal e' velocity increased by 0.7 cm/s (vs. 0.04 in controls, p=0.002)
• Interventricular septal thickness decreased by -1.3 mm (p=0.005)
• NYHA class improved significantly (p=0.031)

This study is particularly notable because it demonstrates diastolic benefits even in a population not traditionally studied in SGLT-2i trials.

Supporting Evidence Across Populations

A 2026 study in HFpEF patients showed that long-term SGLT-2i therapy (≥6 months) produced 4:

• Improved global longitudinal strain (ΔGLS: -2.49% vs. -0.44%, p<0.001)
• E/e' ratio reduction and improved diastolic function
• 30.4% reduction in NT-proBNP (vs. 9.7% in controls)
• 55% lower heart failure rehospitalization rate (24.7% vs. 55.4%, p<0.001)

The improvement in strain correlated with reduction in myocardial fibrosis markers (PⅢNP), suggesting anti-fibrotic mechanisms underlie the diastolic benefits 4.

Mechanism and Clinical Application

How SGLT-2i Improve Diastolic Function

Multiple studies demonstrate consistent improvements in:

• E/e' ratio reduction (marker of left ventricular filling pressure) 3, 4, 5, 6
• Left atrial volume index reduction 6
• Improved left atrial strain parameters (reservoir, conduit, and contractile function) 6
• Reduced NT-proBNP levels 4, 7
• Total atrial conduction time shortening 8

A 2021 meta-analysis confirmed that SGLT-2i significantly improve the E/e' ratio (MD -0.45, p=0.04) and NT-proBNP levels in T2DM patients with or without chronic heart failure, though structural parameters indexed by body surface area showed no significant change 7.

Clinical Algorithm for Use

For patients with diastolic dysfunction:

1. First-line consideration: Patients with T2DM + HFrEF (EF ≤40%)

   • Strong recommendation with high-quality evidence 1, 2
   • Use dapagliflozin or empagliflozin

2. Expanding indications: Patients with T2DM + HFmrEF or HFpEF

   • Growing evidence supports use 4, 6
   • Expect improvements in E/e' ratio, LA function, and symptoms

3. Consider in: T2DM patients with diastolic dysfunction even without overt heart failure

   • Evidence shows improved diastolic parameters 7, 8
   • May prevent progression to clinical heart failure

4. Monitoring parameters:

   • Baseline and 6-month echocardiography (E/e' ratio, LA volume)
   • NT-proBNP levels
   • NYHA functional class
   • Renal function (though studies show acceptable safety profile) 5

Important Caveats and Limitations

Current evidence gaps identified by guidelines 2:

• Preserved or midrange LVEF data still emerging (though newer studies are filling this gap)
• Acute heart failure settings
• Advanced heart failure
• Stage 4-5 kidney disease (though one 2025 study in hemodialysis showed benefits 5)

Safety considerations 1:

• Monitor for severe genitourinary infections
• Rare risk of diabetic ketoacidosis
• No hypoglycemic events reported in recent studies 3, 5

Practical point: The mechanisms underlying diastolic improvement appear related to reduced myocardial fibrosis, improved myocardial energetics, and favorable cardiac remodeling rather than purely glucosuric effects 4, 7. This explains why benefits extend to non-diabetic patients.

Bottom Line for Clinical Practice

Start SGLT-2 inhibitors in diabetic patients with any evidence of diastolic dysfunction, particularly if they have reduced or mildly reduced ejection fraction. The evidence consistently demonstrates improvements in diastolic parameters (E/e' ratio, LA function, NT-proBNP) within 6 months, with corresponding improvements in symptoms and reduced heart failure hospitalizations. While guidelines currently emphasize HFrEF populations, emerging high-quality evidence supports broader application to HFpEF and even pre-heart failure diastolic dysfunction in diabetic patients.