Ertugliflozin

Uses

Ertugliflozin is a SGLT2 inhibitor used to treat type 2 diabetes mellitus.

Ertugliflozin as a monotherapy is indicated to improve the glycemic control in adult patients with type 2 diabetes. 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. 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. 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.

Ertugliflozin is also used to associated treatment for these conditions: Type 2 Diabetes Mellitus

How Ertugliflozin works

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.

Toxicity

The reports from clinical trials have portrait ertugliflozin to be well tolerated and abscent of significant side effects. 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.

Food Interaction

• Avoid excessive or chronic alcohol consumption. Alcohol abuse may increase the risk of ketoacidosis.
• Take with or without food.

[Moderate] GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes.

Hypoglycemia most frequently occurs during acute consumption of alcohol.

Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise.

The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia.

Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion.

By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia.

Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.

A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis.

Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan.

Alcohol should not be consumed on an empty stomach or following exercise.

Ertugliflozin Drug Interaction

Moderate: losartan, glyburide, ethanol, ofloxacinUnknown: pioglitazone, aspirin, aspirin, cyanocobalamin, chlorpheniramine, sulfamethoxazole / trimethoprim, ubiquinone, copper gluconate, acetaminophen / dextromethorphan / diphenhydramine, aspirin, glycerin, heparin, canagliflozin / metformin, tramadol, dulaglutide, cholecalciferol

Ertugliflozin Disease Interaction

Major: liver dysfunction, renal dysfunctionModerate: hypotension, infections

Volume of 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.

Elimination Route

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. 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.

Half Life

The terminal elimination half-life of ertugliflozin is 11-17 hours.

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.

Elimination Route

The total recovery of ertugliflozin was 91% and this elimination route is distributed in a ratio of 50% in the urine and 41% in feces. The recovery of the administered dose was achieved approximately 168 hours after initial administration. Urine elimination occurred very rapidly and 80% of the dosage recovered in urine was obtained after 24 hours. The eliminated dose in urine was composed of seven different major metabolites and the unchanged ertugliflozin as a minor metabolite. The elimination rate in feces was depending on the bowel movements of each patient but 98.5% of the eliminated dose in feces was obtained after 168 hours of initial dosage. This eliminated dose was formed mainly by unchanged ertugliflozin and three other minor metabolites.

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