Ertugliflozin

Last updated

Ertugliflozin
Ertugliflozin.svg
Clinical data
Trade names Steglatro
Other namesPF-04971729, ertugliflozin l-pyroglutamic acid
AHFS/Drugs.com Monograph
License data
Pregnancy
category
Routes of
administration 		By mouth
Drug class Antidiabetic agent
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability ~100%
Protein binding 93.6%
Metabolism UGT1A9, UGT2B7
Metabolites Glucuronides
Elimination half-life ~17 hours
Excretion 41% faeces, 50% urine
Identifiers
  • (1S,2S,3S,4R,5S)-5-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard 100.237.989 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H25ClO7
Molar mass 436.89 g·mol−1
3D model (JSmol)
  • CCOc1ccc(cc1)Cc2cc(ccc2Cl)[C@@]34[C@@H]([C@H]([C@@H]([C@@](O3)(CO4)CO)O)O)O
  • InChI=1S/C22H25ClO7/c1-2-28-16-6-3-13(4-7-16)9-14-10-15(5-8-17(14)23)22-20(27)18(25)19(26)21(11-24,30-22)12-29-22/h3-8,10,18-20,24-27H,2,9,11-12H2,1H3/t18-,19-,20+,21-,22-/m0/s1
  • Key:MCIACXAZCBVDEE-CUUWFGFTSA-N

Ertugliflozin, sold under the brand name Steglatro, is a medication for the treatment of type 2 diabetes. [3] [4]

Contents

The most common side effects include fungal infections of the vagina and other infections of the female reproductive system. [4]

Ertugliflozin is a sodium/glucose cotransporter 2 (SGLT2) inhibitor [3] [4] and is in the class of drugs known as gliflozins. [5]

In the United States, it was approved by the Food and Drug Administration for use as a monotherapy and as a fixed dose combination with either sitagliptin or with metformin. [6] In the European Union, it was approved in March 2018, for use as a monotherapy or combination therapy. [7] In September 2020, The New England Journal of Medicine reported that ertugliflozin was shown to be essentially non-inferior to placebo with respect to cardiovascular events. [8]

A combination with metformin is marketed as Segluromet and a combination with sitagliptin is marketed as Steglujan. [1] [9] [10] [11] [12]


Medical uses

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. [4]

Contraindications

Under the US approval, ertugliflozin is contraindicated for patients with severe kidney failure, end-stage renal disease, and dialysis. [3] The European Union approval does not list any contraindications apart from hypersensitivity to the drug, which is standard for all drug approvals. [7]

Adverse effects

Adverse 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. [3]

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. [13]

Symptoms of ketoacidosis include nausea, vomiting, abdominal pain, tiredness, and trouble breathing. [13]

Overdose

Up to sixfold clinical doses over two weeks, or 20-fold single doses, are tolerated by patients without any toxic effects. [7]

Interactions

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. [3] [7]

Pharmacology

Mechanism of action

Pharmacokinetics

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. [3] [7]

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. [3] [7]

Society and culture

Ertugliflozin, ertugliflozin/metformin, and ertugliflozin/sitagliptin were approved for medical use in the United States in December 2019, and in the European Union in March 2018. [3] [9] [11] [4] [10] [12]

Related Research Articles

<span class="mw-page-title-main">Metformin</span> Medication used to treat diabetes

Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotics. Metformin is not associated with weight gain and is taken by mouth.

Drugs used in diabetes treat diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.

<span class="mw-page-title-main">Sitagliptin</span> Diabetes medication

Sitagliptin, sold under the brand name Januvia among others, is an anti-diabetic medication used to treat type 2 diabetes. In the United Kingdom it is listed as less preferred than metformin or a sulfonylurea. It is taken by mouth. It is also available in the fixed-dose combination medication sitagliptin/metformin.

<span class="mw-page-title-main">Saxagliptin</span> Chemical compound

Saxagliptin, sold under the brand name Onglyza, is an oral hypoglycemic of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. Early development was solely by Bristol-Myers Squibb; in 2007 AstraZeneca joined with Bristol-Myers Squibb to co-develop the final compound and collaborate on the marketing of the drug.

Pioglitazone/metformin, sold under the brand name Actoplus Met among others, is a fixed-dose combination anti-diabetic medication used to improve glycemic control in adults with type 2 diabetes. It contains pioglitazone, a thiazolidinedione, and metformin, a biguanide.

<span class="mw-page-title-main">Dapagliflozin</span> Diabetes medication

Dapagliflozin, sold under the brand names Farxiga (US) and Forxiga (EU) among others, is a medication used to treat type 2 diabetes. It is also used to treat adults with heart failure and chronic kidney disease. It reversibly inhibits sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.

<span class="mw-page-title-main">Rilpivirine</span> HIV treatment

Rilpivirine, sold under the brand names Edurant and Rekambys, is a medication, developed by Tibotec, used for the treatment of HIV/AIDS. It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency, longer half-life and reduced side-effect profile compared with older NNRTIs such as efavirenz.

<span class="mw-page-title-main">Canagliflozin</span> Chemical compound

Canagliflozin, sold under the brand name Invokana among others, is a medication used to treat type 2 diabetes. It is used together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth.

Sitagliptin/metformin, sold under the brand name Janumet among others, is a fixed-dose combination anti-diabetic medication used to treat type 2 diabetes. It may be used in those whose blood sugar is not controlled with metformin and a sulfonylurea. It is taken by mouth.

Empagliflozin, sold under the brand name Jardiance, among others, is an antidiabetic medication used to improve glucose control in people with type 2 diabetes. It is taken by mouth.

<span class="mw-page-title-main">Dulaglutide</span> Diabetes medication

Dulaglutide, sold under the brand name Trulicity among others, is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is also approved in the United States for the reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors. It is a once-weekly injection.

<span class="mw-page-title-main">Empagliflozin/linagliptin</span> Pharmaceutical drug

Empagliflozin/linagliptin, sold under the brand name Glyxambi, is a fixed-dose combination anti-diabetic medication used to treat type 2 diabetes. It is a combination of empagliflozin and linagliptin. It is taken by mouth.

SGLT2 inhibitors are a class of medications that inhibit sodium-glucose transport proteins in the nephron, unlike SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium/glucose cotransporter 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type 2 diabetes. Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in people with type 2 diabetes. As of 2014, several medications of this class had been approved or were under development. In studies on canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure.

Vildagliptin/metformin, sold under the brand name Eucreas among others, is a fixed-dose combination anti-diabetic medication for the treatment of type 2 diabetes. It was approved for use in the European Union in November 2007, and the approval was updated in 2008. It combines 50 mg vildagliptin with either 500, 850, or 1000 mg metformin.

Empagliflozin/metformin, sold under the brand name Synjardy among others, is a fixed-dose combination anti-diabetic medication used to treat type 2 diabetes. It contains empagliflozin and metformin hydrochloride. It is taken by mouth.

Empagliflozin/linagliptin/metformin, sold under the brand name Trijardy XR, is a drug combination used for the treatment of type 2 diabetes. It is a combination of empagliflozin, linagliptin, and metformin. Empagliflozin/linagliptin/metformin was approved for use in the United States in January 2020.

Dapagliflozin/metformin, sold under the brand name Xigduo XR amongst others, is a fixed-dose combination anti-diabetic medication used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. It is a combination of dapagliflozin and metformin and is taken by mouth. Dapagliflozin/metformin was approved for use in the European Union in January 2014, in the United States in February 2014, and in Australia in July 2014.

Canagliflozin/metformin, sold under the brand name Vokanamet among others, is a fixed-dose combination anti-diabetic medication used for the treatment of type 2 diabetes. It is used in combination with diet and exercise. It is taken by mouth.

Pioglitazone/glimepiride, sold under the brand name Duetact among others, is a fixed-dose combination anti-diabetic medication for the treatment of type 2 diabetes. It contains the thiazolidinedione pioglitazone and the sulfonylurea glimepiride. It is taken by mouth.

Bexagliflozin, sold under the brand name Brenzavvy, is an antidiabetic medication used to improve glycemic control in adults with type 2 diabetes. It is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that is taken by mouth.

References

  1. 1 2 Australian Public Assessment Report for Ertugliflozin, Ertugliflozin / Sitagliptin, Ertugliflozin / Metformin (PDF) (Report).
  2. ↑ "Drug and medical device highlights 2018: Helping you maintain and improve your health". Health Canada . 14 October 2020. Retrieved 17 April 2024.
  3. 1 2 3 4 5 6 7 8 9 "Steglatro- ertugliflozin tablet, film coated". DailyMed. 30 January 2020. Retrieved 24 September 2020.
  4. 1 2 3 4 5 6 "Steglatro EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 24 September 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. ↑ Trum M, Wagner S, Maier LS, Mustroph J (June 2020). "CaMKII and GLUT1 in heart failure and the role of gliflozins". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1866 (6): 165729. doi: 10.1016/j.bbadis.2020.165729 . PMID   32068116. S2CID   211159566.
  6. ↑ "FDA Approves SGLT2 Inhibitor Ertugliflozin for Type 2 Diabetes". MedScape.
  7. 1 2 3 4 5 6 "Steglatro: EPAR – Product Information" (PDF). European Medicines Agency. 4 June 2018. Archived from the original (PDF) on 18 June 2018. Retrieved 18 June 2018.
  8. ↑ 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.
  9. 1 2 "Segluromet- ertugliflozin and metformin hydrochloride tablet, film coated". DailyMed. 11 August 2020. Retrieved 24 September 2020.
  10. 1 2 "Segluromet EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 24 September 2020.
  11. 1 2 "Steglujan- ertugliflozin and sitagliptin tablet, film coated". DailyMed. U.S. National Library of Medicine. 31 January 2020. Retrieved 24 September 2020.
  12. 1 2 "Steglujan EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 24 September 2020.
  13. 1 2 "FDA revises labels of SGLT2 inhibitors for diabetes to include warning". U.S. Food and Drug Administration. 19 March 2020. Retrieved 6 June 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.