SGLT2 Inhibitors in Heart Failure, CKD, and Diabetes

Primary Indication: First-Line Therapy Regardless of Glycemic Control

The American Diabetes Association and Kidney Disease: Improving Global Outcomes (KDIGO) recommend SGLT2 inhibitors as first-line therapy to prevent CKD progression and cardiovascular events in patients with type 2 diabetes and CKD, independent of baseline HbA1c or current glycemic control 1, 2
SGLT2 inhibitors reduce cardiovascular death, heart failure hospitalizations, and progression of kidney disease through mechanisms beyond glucose lowering, including reduction in intraglomerular pressure and improved tubuloglomerular feedback 1, 3
The KDIGO 2022 guidelines position SGLT2 inhibitors as first-line drug therapy based on 11 published clinical trials demonstrating strong evidence of efficacy 1

Initiate SGLT2 inhibitors in patients with eGFR ≥20 mL/min/1.73 m², with strongest evidence for those with concomitant albuminuria or heart failure 2, 3
Eligible patients include those with eGFR ≥20 mL/min/1.73 m², with high priority for patients with ACR ≥200 mg/g (≥20 mg/mmol) 1
Once initiated, continue SGLT2 inhibitors even if eGFR falls below 20 mL/min/1.73 m², unless kidney replacement therapy is initiated 3

For heart failure with reduced ejection fraction (LVEF ≤40%), SGLT2 inhibitors reduce cardiovascular death and heart failure hospitalization (Class 1 recommendation) 4
SGLT2 inhibitors decrease heart failure hospitalizations (Class 2a recommendation) for heart failure with preserved ejection fraction (LVEF >40%) 4

SGLT2 inhibitors reduce the composite kidney outcome (≥50% eGFR decline, ESKD, or renal death) by 44% (HR 0.56) 2
The DAPA-CKD trial showed a 39% risk reduction for the primary endpoint and 32% risk reduction for development of ESKD 2

Counsel patients about increased risk of genital yeast infections (6% vs 1% placebo) and importance of proper genital hygiene 3, 5
Contraindications include severe renal impairment (eGFR <20 mL/min/1.73 m²), ESKD, dialysis, and history of serious hypersensitivity reaction 5

SGLT2 inhibitors can be used concomitantly with RAS inhibitors and nonsteroidal mineralocorticoid receptor antagonists (ns-MRA) like finerenone 1
The cardiovascular effects of finerenone appeared at least as beneficial among people using versus not using an SGLT2 inhibitor 1

However, cardiovascular and renal benefits persist at low eGFR independent of glucose-lowering effects, making continuation appropriate even when glycemic benefit is minimal 2, 3, 4

The American Diabetes Association recommends against initiating SGLT2 inhibitors in patients with normal albumin/creatinine ratio (<30 mg/g) and no evidence of chronic kidney disease, with a Grade A recommendation 6, 7, 8
Patients with established heart failure or cardiovascular disease may be considered for SGLT2 inhibitors for cardiovascular risk reduction, with a strong indication for heart failure 9
The American Diabetes Association recommends annual screening for albuminuria and eGFR in patients with normal kidney function, with a Grade A recommendation 6, 7, 8

SGLT2 inhibitors are recommended for patients with chronic kidney disease (eGFR ≥20 mL/min/1.73 m²) and albuminuria (≥30 mg/g), with a strong indication (Grade A) for urinary albumin ≥200 mg/g creatinine 6, 7
Patients with established cardiovascular disease or heart failure may be considered for SGLT2 inhibitors, with a moderate indication (Grade B) for cardiovascular risk reduction 9

Patients with normal kidney function should be monitored annually for albuminuria and eGFR, with a Grade A recommendation 6, 7, 8
SGLT2 inhibitors should be reconsidered if albuminuria develops (≥30 mg/g), eGFR declines (<60 mL/min/1.73 m²), or heart failure or cardiovascular disease develops 6, 7, 9