|Other names||PF-04971729, ertugliflozin l-pyroglutamic acid|
|Drug class||SGLT2 inhibitor|
|Main uses||Type 2 diabetes|
|Side effects||Fungal infections of the vagina, diabetic ketoacidosis (DKA), limb amputation, Fournier's gangrene|
|Typical dose||5 to 15 mg OD|
|Elimination half-life||~17 hours|
|Excretion||41% faeces, 50% urine|
|Chemical and physical data|
|Molar mass||436.89 g·mol−1|
|3D model (JSmol)|
Ertugliflozin, sold under the brand name Steglatro, is a medication used to treat type 2 diabetes. It is used together with diet and exercise. It is taken by mouth. It should not be used in people with type 1 diabetes.
Common side effects include fungal infections of the vagina and other infections of the female reproductive system. Other side effects may include diabetic ketoacidosis (DKA), limb amputation, and Fournier's gangrene. Use in pregnancy is not recommended. It is a sodium glucose cotransporter 2 (SGLT2) inhibitor which increases the amount of glucose lost in the urine.
Ertugliflozin was approved for medical use in the United States in 2017 and Europe in 2018. In the United Kingdom 4 weeks of medication costs the NHS about £30 as of 2021. This amount in the United States is 280 USD.
Steglatro is indicated for the treatment of adults with insufficiently controlled type 2 diabetes as an adjunct to diet and exercise as monotherapy when metformin is considered inappropriate due to intolerance or contraindications or in addition to other medicinal products for the treatment of diabetes.
It is started at a dose of 5 mg per day which may be increased to 15 mg per day.
Ertugliflozin is contraindicated for patients with severe kidney failure, end-stage renal disease, and dialysis. The European Union approval does not list any contraindications apart from hypersensitivity to the drug, which is standard for all drug approvals.
Side effects in studies that were significantly more common under ertugliflozin than under placebo included mycosis of the genitals in both men and women, vaginal itch, increased urination, thirst, hypoglycaemia (low blood sugar), and weight loss under the higher dosing scheme. A rare but life-threatening side effect of gliflozins is ketoacidosis; it occurred in three patients (0.1%) in ertugliflozin studies.
To lessen the risk of developing ketoacidosis (a serious condition in which the body produces high levels of blood acids called ketones) after surgery, the FDA has approved changes to the prescribing information for SGLT2 inhibitor diabetes medicines to recommend they be stopped temporarily before scheduled surgery. Ertugliflozin should be stopped at least four days before scheduled surgery.
Symptoms of ketoacidosis include nausea, vomiting, abdominal pain, tiredness, and trouble breathing.
Up to sixfold clinical doses over two weeks, or 20-fold single doses, are tolerated by people without any toxic effects.
As with many diabetes drugs, combining ertugliflozin with insulin or insulin secretagogues (such as sulfonylureas) may result in an increased risk for low blood sugar. Combination with diuretics may result in a higher risk for dehydration and low blood pressure. No clinically relevant pharmacokinetic interactions have been found in studies.
Mechanism of action
After oral intake, ertugliflozin is practically completely absorbed from the gut and undergoes no relevant first-pass effect. Highest blood plasma concentrations are reached after one hour. When in circulation, 93.6% of the substance are bound to plasma proteins. Ertugliflocin is metabolised mainly to glucuronides by the enzymes UGT1A9 and UGT2B7. Cytochrome P450 enzymes play only a minor role in its metabolism.
The elimination half-life is estimated to be 17 hours. 40.9% are eliminated via the feces (33.8% in unchanged form and 7.1% as metabolites) and 50.2% via the urine (1.5% unchanged and 48.7% as metabolites). The high proportion of unchanged substance in the feces is probably due to hydrolysis of the metabolites back to the parent substance.
Society and culture
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- BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 749. ISBN 978-0857114105.
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- Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, et al. (October 2020). "Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes". The New England Journal of Medicine. 383 (15): 1425–1435. doi:10.1056/NEJMoa2004967. PMID 32966714.
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- "Steglatro: EPAR – Product Information" (PDF). European Medicines Agency. 4 June 2018. Archived (PDF) from the original on 18 June 2018. Retrieved 30 September 2021.
- "FDA revises labels of SGLT2 inhibitors for diabetes to include warning". U.S. Food and Drug Administration. 19 March 2020. Archived from the original on 7 June 2020. Retrieved 6 June 2020. This article incorporates text from this source, which is in the public domain.