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