Empagliflozin: Novel antidiabetes and pro-cardiac drug.

Sir,

Diabetes mellitus is associated with significant cardiovascular (CV) morbidity and mortality. Empagliflozin is the first Food and Drug Administration-approved antidiabetes drug to decrease the risk of CV mortality in patients with type 2 diabetes and CV disease.

Empagliflozin has been shown to improve glycaemic control and reduce CV mortality along with salutary effects on renal outcomes as compared to placebo in a recently conducted EMPA-REG OUTCOME trial in a large number of patients.[12] In this study, more than 7000 patients were randomly assigned to receive empagliflozin in the dose of 10 mg or 25 mg or placebo once daily. Patients were followed up over a median observation time of 3.1 years. Patients in the empagliflozin group suffered significantly lower rates of CV death (3.7% vs. 5.9% in the placebo group; 38% relative risk reduction), death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction) and hospitalisation for heart failure (HF) (2.7% and 4.1%, respectively; 35% relative risk reduction). Diabetic patients prone to CV events who received empagliflozin along with standard care had a reduced rate of the primary composite CV outcome and death from any cause, when compared with placebo.

Renal tubular sodium glucose cotransport receptors (SGLT2 receptors) cause increased tubular glucose reabsorption. These receptors are upregulated in type 2 diabetes. More sodium reabsorption in the proximal renal tubules results in low sodium delivery to the macula densa, which results in vasodilation of the afferent arteriole with vasoconstriction of the efferent arteriole causing intraglomerular hypertension. Inhibition of SGLT2 receptors by empagliflozin abolishes the above effects and explains its cardiorenal benefits in such patients.[12345] Simultaneous reduction in both preload (by diuresis) and afterload (by decreasing arterial stiffness and blood pressure) could likely to have resulted in the reduction of CV mortality by empagliflozin. Analysis from EMPA-REG OUTCOME also suggested that positive change in haemoglobin/haematocrit was most likely associated with both improved HF and death risk.[34] It is also hypothesised that empagliflozin improves cardiac fuel metabolism, by shifting energy substrate utilisation away from glucose and lipids towards ketone bodies that produce more ATP energy than glucose or FFA, thereby increasing myocardial contractility and cardiac efficiency.[4]

To reduce CV risk, many evidence-based treatments are available such as lipid-lowering agents, antihypertensives and antiplatelet aspirin. Empagliflozin can be a potential game changer to decrease CV risk in diabetic patients. Glucose in urine is generally regarded as a poor control of diabetes, but now we need to get used to the finding of glucosuria induced by empagliflozin for the control of diabetes. Oral hypoglycaemic drugs are not used in the perioperative period; however considering the prominent CV benefits, empagliflozin can be useful perioperatively although future research studies are warranted.

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Conflicts of interest

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