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8h
Cardiorenal-metabolic therapy in cardiovascular disease: SGLT2 inhibitor and nonsteroidal MRA synergy in heart failure

Cardiovascular disease remains the leading cause of global mortality. SGLT2 inhibitors and GLP-1 receptor agonists have become foundational agents across heart failure, chronic kidney disease, and atherosclerotic cardiovascular risk reduction.

The FINEARTS-HF trial demonstrated that a nonsteroidal mineralocorticoid receptor antagonist (nsMRA) reduces the composite of worsening heart failure events and cardiovascular death in HFmrEF/HFpEF, with consistent benefit irrespective of SGLT2 inhibitor use, supporting additive cardiorenal protection with combination therapy. A comparative real-world study of 364,714 patients with type 2 diabetes at moderate cardiovascular risk found SGLT2 inhibitors superior to GLP-1 receptor agonists for kidney composite outcomes (HR 0.81), with both superior to DPP-4 inhibitors and sulfonylureas. These data support individualized, guideline-directed combination strategies targeting the cardiovascular, renal, and metabolic axes of disease.

Cardiologists, endocrinologists, nephrologists, and primary care physicians managing CVD with cardiometabolic comorbidities will benefit from peer discussion of combination therapy evidence, guideline-directed medical therapy optimization, and individualized cardiorenal risk reduction.

How does emerging evidence for SGLT2 inhibitor and nonsteroidal mineralocorticoid receptor antagonist combination therapy influence your treatment algorithm for patients with HFmrEF or HFpEF? How do you prioritize and sequence SGLT2 inhibitors versus GLP-1 receptor agonists in patients with cardiovascular disease and type 2 diabetes, and what cardiorenal risk factors most influence this decision?

  • 8h
    Choice of GLP-1 when weight is a factor in patients mental and physical health. SGLT2 is when diabetes is present along with CKD and proteinuria and HF. Non-steroid MRA is chosen when HF is the major issue.
  • 3d
    If patients have a lot of weight to lose, and a greater A1c decrease is needed, I preferentially utilize GLP1 therapy over SGLT2 therapies. I certainly would prefer combo SGLT2 and mineralocorticoid receptor agonist therapy to achieve greater symptom control with less pill burden, if cost is not prohibitive, and significant A1c reduction is not needed.
  • 1w
    SGLT2i is the foundational, near-universal agent. Both DELIVER (dapagliflozin) and EMPEROR-Preserved (empagliflozin) showed an 18–21% reduction in HF hospitalization/cardiovascular death across the LVEF ≥40% spectrum, in patients with and without diabetes. Guidelines recommend it for essentially all HFpEF/HFmrEF patients without contraindication, with rapid onset, minimal monitoring, and favorable renal effects
  • 2w
    I usually try to use both treatments in patients to complete GDMT and optimize probability of improved LV function.
  • 2w
    I use them together to decrease incidence of cvd, renal compromise.
  • 2w
    makes you a lot more likely to go to combination therapy earlier.
    Use SGLT earlier in renal disease and heart failure and GLP earlier in sleep apnea and with obesity.
  • 3w
    I use SGLT2 inhibitors early in patients with heart failure or chronic kidney disease because they provide strong heart and kidney protection. If appropriate, I add a nonsteroidal mineralocorticoid receptor antagonist to further reduce the risk of heart failure worsening and cardiovascular events. For patients with type 2 diabetes and cardiovascular disease, I choose between an SGLT2 inhibitor and a GLP-1 receptor agonist based on whether heart failure, kidney disease, or atherosclerotic cardiovascular disease is the main concern, while also considering patient preferences, side effects, kidney function, and cost.

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