Cardiovascular Benefits of SGLT2 Inhibitors in Diabetes

Type 2 diabetes is a leading contributor to cardiovascular morbidity and mortality worldwide, with diabetic cardiomyopathy and heart failure representing major clinical challenges. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, originally developed to lower blood glucose by promoting renal glucose excretion, have demonstrated substantial cardiovascular benefits that extend beyond glycaemic control. Large outcome trials have consistently shown reductions in heart failure hospitalisations and cardiovascular death, even in patients without a prior history of heart failure. Proposed mechanisms include favourable haemodynamic effects through mild diuresis and natriuresis, improved myocardial energy utilisation via a shift towards ketone bodies, attenuation of oxidative stress and inflammation, preservation of mitochondrial integrity, modulation of ion-homeostasis and promotion of autophagic clearance. These pleiotropic actions converge to improve both systolic and diastolic function, stabilise coronary microcirculation and reduce cardiac fibrosis, offering a novel paradigm for the management of diabetic cardiac disease.

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Cardiovascular Benefits of SGLT2 Inhibitors in Diabetes publication trend

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Technical terms

Sodium–glucose cotransporter 2 (SGLT2) inhibitor: A class of oral antidiabetic agents that lowers blood glucose by blocking glucose reabsorption in the renal proximal tubule.

Diabetic cardiomyopathy: Structural and functional abnormalities of the myocardium in diabetic patients, independent of coronary artery disease or hypertension.

Mitochondrial fission: Division of mitochondria into smaller units, a process that can be maladaptive when excessive, leading to impaired energy production and increased oxidative stress.

Autophagy: A regulated intracellular degradation pathway that recycles damaged organelles and protein aggregates, crucial for cellular homeostasis under stress.

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen that, in excess, cause oxidative damage to DNA, lipids and proteins.

References

1. Potential mechanisms responsible for cardioprotective effects of sodium–glucose co-transporter 2 inhibitors. Cardiovascular Diabetology (2018).
2. Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms. Cardiovascular Diabetology (2023).
3. Empagliflozin attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial homeostasis. Cardiovascular Diabetology (2022).
4. SGLT2 Inhibitors and Their Mode of Action in Heart Failure—Has the Mystery Been Unravelled?. Current Heart Failure Reports (2021).