New Insights into the Use of Empagliflozin—A Comprehensive Review

Abstract

Empagliflozin is a relatively new drug that, as an inhibitor of the sodium–glucose cotransporter 2 (SGLT2), causes increased urinary glucose excretion and thus contributes to improved glycemic control, better glucose metabolism, reduced glucotoxicity and insulin resistance. Although its original use was to induce a hypoglycemic effect in patients with type 2 diabetes mellitus (T2DM), empagliflozin has also shown a number of other beneficial effects by demonstrating a nephroprotective effect, and it has proven to be a breakthrough in the treatment of heart failure (HF). Empagliflozin has been shown to reduce hospitalizations for HF and the number of deaths from cardiovascular causes. Empagliflozin treatment also reduces the incidence of renal events, including death from renal causes, as well as the risk of end-stage renal failure. Empagliflozin appears to be a fairly well-tolerated and safe drug. In patients with inadequate glycemic control, empagliflozin used in monotherapy or as an adjunct to therapy effectively lowers fasting blood glucose, postprandial blood glucose, average daily glucose levels, glycated hemoglobin A1C (HbA1C) and also leads to significant weight reduction in patients with T2DM. Unfortunately, there are some limitations, e.g., severe hypersensitivity reaction to the drug and a glomerular filtration rate (GFR) < 30 mL/min/1.73m2. As with any drug, empagliflozin is also characterized by several side effects among which symptomatic hypotension, troublesome genital fungal infections, urinary tract infections and rare ketoacidosis are characteristic.

Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders

“…Subsequent studies confirmed that the glucosuric effects of empagliflozin resulted in a decrease of plasma glucose levels (38)(39)(40)(41), glycemic spikes and HbA1c levels (42). However, empagliflozin has pleiotropic effects, such as reducing insulin levels, insulin resistance, glucotoxicity and lipotoxicity, and increasing glucagon secretion and ketone bodies production (42,43). Furthermore, empagliflozin improves redox state and oxidative stress, inhibiting reactive oxygen species (ROS) production, reducing the activity of pro-oxidant agents, and improving mitochondrial function (44).…”

“…Chronic dosing shifted the substrate utilization from carbohydrates to lipids (37). Subsequent studies confirmed that the glucosuric effects of empagliflozin resulted in a decrease of plasma glucose levels (38)(39)(40)(41), glycemic spikes and HbA1c levels (42). However, empagliflozin has pleiotropic effects, such as reducing insulin levels, insulin resistance, glucotoxicity and lipotoxicity, and increasing glucagon secretion and ketone bodies production (42,43).…”

“…Furthermore, empagliflozin improves redox state and oxidative stress, inhibiting reactive oxygen species (ROS) production, reducing the activity of pro-oxidant agents, and improving mitochondrial function (44). Of note, all these processes are implicated in the pathogenesis of metabolic, cardiovascular (CV), renal and neurological consequences of diabetes (42,45). Particularly, in diabetes and obesity the excessive circulating free fatty acids accumulate in the adipose tissue mainly as TG.…”

“…Furthermore, the non-fasting hyperlipidemia causes endothelial stress through the production of inflammatory cytokines and oxidative stress agents, and the reduction of endothelial nitric oxide synthase activity (48,49). Empagliflozin exerts protective effects from lipotoxicity, decreasing lipid accumulation in visceral fat (43) and promoting weight loss (50), reducing inflammation and oxidative stress (42).…”

Nitrene‐Mediated Enantioselective Intramolecular Olefin Oxyamination to Access Chiral γ‐Aminomethyl‐γ‐Lactones

“…Chemie thalene-containing γ-lactone 29 was afforded in moderate 64 % yield with 37 % ee. Furthermore, involving a scaffold of bioactive compounds provided empagliflozin [14] derivative 30 in 74 % yield with 16 : 1 dr and a canagliflozin [15] derivative 31 in 78 % yield with 83 % ee. Last but not least, non-activated olefins devoid of an aryl or alkynyl substituent were investigated.…”