Ertugliflozin 1210344-83-4 type 2 diabetes

Egliflozin is a novel SGLT2 inhibitor drug jointly developed by Pfizer and Merck. In December 2017, the Chemicalbook was approved by the US FDA for marketing, with the trade name Steglatro. It is clinically used for the treatment of adult patients with type 2 diabetes. When metformin hydrochloride alone is used to control blood sugar poorly, this product can be used in combination with metformin hydrochloride to improve the blood sugar control of adult patients with type 2 diabetes with diet and exercise. Drug restriction: This product is not recommended for the treatment of type 1 diabetes patients or diabetes ketoacidosis.

The summary of placebo controlled trial data for evaluating the safety of Etogliflozin 5mg and 15mg in clinical trials is presented in Table 1. The data comes from three 26 week placebo-controlled trials, which reflect the exposure of the product in 1029 patients, with an average exposure time of approximately 25 weeks. The patient received treatment with Etogliflozin 5 mg (N=519), Etogliflozin 15 mg (N=510), or placebo (N=515) once daily. The average age of this population is 57 years old, and 2% of patients are over 75 years old. 53% of this population is male, 73% is Caucasian, 15% is Asian, and 7% is black or African American. At baseline, the average duration of diabetes in this population was 7.5 years, the average value of HbA1c was 8.1%, and 19.4% of the patients were confirmed to have microvascular complications of diabetes; 97% of patients have normal or mild renal function impairment (average eGFR of 88.9 mUmin/1.73m2), and 3% of patients have moderate renal insufficiency.

Sodium glucose co transporter 2 (SGLT2) is the main transporter responsible for reabsorbing glucose from glomerular filtrate back into the systemic circulation. Etogliflozin is an SGLT2 inhibitor that inhibits SGLT2, reduces renal reabsorption of filtered glucose, lowers the renal threshold of glucose, and thus increases urinary glucose excretion. Toxicological studies on repeated administration toxicity. In repeated administration toxicity tests in rats and dogs, the main adverse reactions include pharmacological effects such as weight and body fat loss, increased food intake, diarrhea, dehydration, decreased blood sugar, as well as gluconeogenesis and electrolyte disruption related to enhanced protein metabolism, as well as changes in urine such as polyuria, urine sugar, and urine calcium. In a 3-month repeated administration toxicity test in rats, a dose of ≥ 25 mg/kg/d showed an increase in kidney weight, renal tubular dilation, hypertrophy of the adrenal glomerular zone, increased bone trabeculae, gastric ulcer/erosion, proliferation and crypt degeneration of the pyloric fovea, and reduction of pancreatic enzyme granules. The dose of 5 mg/kg/d (NOAEL) with no adverse reactions observed in this test was approximately 12 times the maximum recommended dose (MRHD) of 15 mg/d in humans, according to AUC calculations. Dogs were given Etogliflozin 150 mg/kg/d for 9 consecutive menstrual periods (approximately 379 times MRHD 15 mg/d according to AUC calculation), and no adverse reactions were observed. Juvenile rats were orally administered etogliflozin from 21 days to 90 days after birth. At a dose of ≥ 5 mg/kg (equivalent to 13 times the human exposure according to AUC calculation), renal weight increased, renal tubules and pelvis dilated, and renal mineralization were observed. Rats can cause the above-mentioned changes during the middle and late stages of kidney development, which are equivalent to human kidney development. They may not fully recover within a one month recovery period. Reproductive toxicity: In fertility and embryonic development experiments in rats, male and female rats were orally administered etoglitazone at doses of 5, 25, and 250 mg/kg/d (according to AUC calculations, males and females were approximately 480 and 570 times higher than MRHD15 mg/d), and no effect on fertility was found. In the embryonic fetal developmental toxicity test, rats were given 50, 100, and 250 mg/kg/d of etoglitazone orally on gestational days 6-17 and rabbits were given 7-19. According to AUC calculations, no adverse effects were found on the development of rats and rabbits when the maternal exposure levels were 300 times equivalent to MRHD 15 mg/d.