Singapore Drugs Database

Indication

Ertugliflozin as a monotherapy is indicated to improve the glycemic control in adult patients with type 2 diabetes.[FDA label] Ertugliflozin, in combination with metformin hydrochloride, is indicated to improve glycemic control in patients with diabetes type 2 who are not controlled on a regimen of ertugliflozin or metformin or in patients who are already treated with both ertugliflozin and metformin.[L1134] The administration of ertugliflozin in combination with sitagliptin is indicated to improve glycemic control in adult patients with type 2 diabetes when treatment with ertugliflozin and sitagliptin is appropriate.[L1135] It is pointed out that the use of ertugliflozin has to be an adjunct therapy to the use of diet and exercise. The type 2 diabetes mellitus is characterized by insulin resistance in muscle and liver, which results in the elevation of glucose levels in blood, or by presence of insulin deficiency. The insulin resistance is related to genetic factors, obesity, sedentary lifestyle or/and aging. This increase in the blood glucose can cause severe damage to kidney, eyes and vascular system.[A31582]

Mechanism of Action

As part of a normal process, the glucose from the blood is filtered for excretion and reabsorbed in the glomerulus so less than one percent of this glucose is excreted in the urine. The reabsorption is mediated by the sodium-dependent glucose cotransporter (SGLT), mainly the type 2 which is responsible for 90% of the reabsorbed glucose. Ertugliflozin is a small inhibitor of the SGLT2 and its activity increases glucose excretion, reducing hyperglycemia without the requirement of excessive insulin secretion.[A31581]

Pharmacokinetics

Absorption

Preclinical studies showed that ertugliflozin is well absorbed and had an oral bioavailability of 70-90%. The reported Tmax occurred at 0.5-1.5 hours after dosage.[A31583] Following oral administration, the Cmax and AUC appeared to be dose proportional.Administration of 15 mg reported values of Cmax and AUC of 268 ng/ml and 1193 ng h/ml respectively.[L1136]

Distribution

After oral administration of ertugliflozin, the apparent volume of distribution was reported to be 215.3 L. The steady-state volume of distribution after intravenous administration of etrugliflozin is 85.53 L.[L1136]

Metabolism

In vitro studies showed that the metabolic profile of ertugliflozin in liver microsomes and hepatocytes is formed by reactions of monohydroxylation, O-demethylation and glucuronidation. The metabolism of ertugliflozin is proposed to be formed by 8 different metabolites found in plasma, feces and urine. In plasma, the unchanged form of ertugliflozin was found to be the major component of the administered dose. There were also other six minor metabolites identified in circulating plasma.[A31583]

Elimination

Clearance

The apparent total plasma clearance rate after oral administration of ertugliflozin is 178.7 ml/min and the systemic total plasma clearance after intravenous administration is reported to be 187.2 ml/min.[L1136]

Toxicity

The reports from clinical trials have portrait ertugliflozin to be well tolerated and abscent of significant side effects.[A31586] Carcinogenic studies have been performed and it has been reported an increased incidence of adrenal medullary pheochromocytoma; possibly related to carbohydrate malabsorption leading to altered calcium homeostasis. There were no reported cases of mutagenesis or impairment in fertility.[FDA label]

Active Ingredient/Synonyms

Ertugliflozin | Ertugliflozin |