J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Review

Volume 16, Number 9, September 2024, pages 398-410

Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular and Renal Outcomes in Heart Failure Patients With Type 2 Diabetes: A Literature Review

↓ **Table 1.** Summary of Major Clinical Trials on SGLT2 Inhibitors
Study	Population	Key findings	Relevance to HF management in T2D
ASCVD: atherosclerotic cardiovascular disease; CV: cardiovascular; HF: heart failure; HFrEF: heart failure with reduced ejection fraction; MI: myocardial infarction; SGLT2: sodium-glucose cotransporter 2; T2D: type 2 diabetes.
EMPA-REG OUTCOME	T2D patients with high cardiovascular risk	Reduced cardiovascular death by 38%, reduced hospitalization for heart failure by 35%	Demonstrates significant cardiovascular benefits of empagliflozin in high-risk patients
CANVAS	T2D patients with high cardiovascular risk	Reduced hospitalization for heart failure by 33%, improved renal outcomes	Highlights the dual cardiovascular and renal benefits of canagliflozin
DECLARE-TIMI 58	T2D patients with or at risk for ASCVD	Reduced cardiovascular death or hospitalization for heart failure by 17%, significant renal benefits	Shows dapagliflozin’s effectiveness in a broader T2D population
DAPA-HF	HFrEF patients, with and without T2D	Reduced risk of worsening HF or CV death by 26%	Indicates dapagliflozin’s benefits in heart failure irrespective of diabetic status
CREDENCE	T2D patients with chronic kidney disease	Reduced risk of renal failure by 34%, reduced risk of CV death, MI, or stroke by 20%	Emphasizes canagliflozin’s role in protecting against renal and cardiovascular outcomes
VERTIS CV	T2D patients with established cardiovascular disease	Non-inferior to placebo for primary CV outcomes, improved glycemic control	Supports ertugliflozin’s cardiovascular safety and efficacy in glucose management

↓ Table 1. Summary of Major Clinical Trials on SGLT2 Inhibitors

Study

Population

Key findings

Relevance to HF management in T2D

ASCVD: atherosclerotic cardiovascular disease; CV: cardiovascular; HF: heart failure; HFrEF: heart failure with reduced ejection fraction; MI: myocardial infarction; SGLT2: sodium-glucose cotransporter 2; T2D: type 2 diabetes.

EMPA-REG OUTCOME

T2D patients with high cardiovascular risk

Reduced cardiovascular death by 38%, reduced hospitalization for heart failure by 35%

Demonstrates significant cardiovascular benefits of empagliflozin in high-risk patients

CANVAS

T2D patients with high cardiovascular risk

Reduced hospitalization for heart failure by 33%, improved renal outcomes

Highlights the dual cardiovascular and renal benefits of canagliflozin

DECLARE-TIMI 58

T2D patients with or at risk for ASCVD

Reduced cardiovascular death or hospitalization for heart failure by 17%, significant renal benefits

Shows dapagliflozin’s effectiveness in a broader T2D population

DAPA-HF

HFrEF patients, with and without T2D

Reduced risk of worsening HF or CV death by 26%

Indicates dapagliflozin’s benefits in heart failure irrespective of diabetic status

CREDENCE

T2D patients with chronic kidney disease

Reduced risk of renal failure by 34%, reduced risk of CV death, MI, or stroke by 20%

Emphasizes canagliflozin’s role in protecting against renal and cardiovascular outcomes

VERTIS CV

T2D patients with established cardiovascular disease

Non-inferior to placebo for primary CV outcomes, improved glycemic control

Supports ertugliflozin’s cardiovascular safety and efficacy in glucose management

↓ **Table 2.** Mechanisms of Action of SGLT2 Inhibitors
Mechanism	Description
SGLT2: sodium-glucose cotransporter 2.
Glucosuria	Increased glucose excretion in urine, leading to improved glycemic control
Natriuresis	Increased sodium excretion, leading to reduced plasma volume and blood pressure
Anti-inflammatory	Reduction in adipose tissue-mediated inflammation and oxidative stress
Cardiovascular benefits	Improved cardiac energy metabolism, reduced vascular resistance

↓ Table 2. Mechanisms of Action of SGLT2 Inhibitors

Mechanism

Description

SGLT2: sodium-glucose cotransporter 2.

Glucosuria

Increased glucose excretion in urine, leading to improved glycemic control

Natriuresis

Increased sodium excretion, leading to reduced plasma volume and blood pressure

Anti-inflammatory

Reduction in adipose tissue-mediated inflammation and oxidative stress

Cardiovascular benefits

Improved cardiac energy metabolism, reduced vascular resistance

↓ **Table 3.** Clinical Benefits of SGLT2 Inhibitors
Benefit	Description
HbA1c: hemoglobin A1c; SGLT2: sodium-glucose cotransporter 2.
Glycemic control	Improved HbA1c levels
Cardiovascular	Reduced cardiovascular mortality and major adverse cardiovascular events
Renal	Improved renal outcomes, reduced albuminuria and glomerular hyperfiltration

↓ Table 3. Clinical Benefits of SGLT2 Inhibitors

Benefit

Description

HbA1c: hemoglobin A1c; SGLT2: sodium-glucose cotransporter 2.

Glycemic control

Improved HbA1c levels

Cardiovascular

Reduced cardiovascular mortality and major adverse cardiovascular events

Renal

Improved renal outcomes, reduced albuminuria and glomerular hyperfiltration

↓ **Table 4.** Patient Outcomes Associated With SGLT2 Inhibitors
Outcome	Description
SGLT2: sodium-glucose cotransporter 2.
Mortality	Reduced all-cause and cardiovascular mortality
Hospitalizations	Reduced hospitalizations for heart failure
Adverse events	Increased risk of genital infections, diabetic ketoacidosis

↓ Table 4. Patient Outcomes Associated With SGLT2 Inhibitors

Outcome

Description

SGLT2: sodium-glucose cotransporter 2.

Mortality

Reduced all-cause and cardiovascular mortality

Hospitalizations

Reduced hospitalizations for heart failure

Adverse events

Increased risk of genital infections, diabetic ketoacidosis