Ertugliflozin: The Key to Managing Type 2 Diabetes Mellitus

Overview:

Combining Ertugliflozin with a healthy diet and regular exercise helps persons with type 2 diabetes reduce their elevated blood sugar levels. It is a member of the class of drugs called inhibitors of the sodium-glucose co-transporter 2 (SGLT2). These medications help control diabetes by supporting the kidneys in eliminating extra sugar from the body through urine. Ertugliflozin was approved by the US FDA (Food and Drug Administration) in December 2017.

Indications:

When taken with a balanced diet and frequent exercise, Ertugliflozin helps persons with type 2 diabetes control their blood sugar levels.

Contraindications:

• Severe Kidney Damage: This indicates an impairment of the kidneys.

• End-Stage Renal Disease (ESRD): In this stage of renal disease, the kidneys have nearly stopped functioning altogether.

• Dialysis: This is a kidney failure treatment where the blood is cleaned and filtered by a machine because the kidneys cannot do it well.

• Ertugliflozin-Related Severe Hypersensitivity Reaction History: This indicates that the patient has experienced a negative response to Ertugliflozin in the past. A hypersensitivity reaction is when the immune system reacts too strongly or exaggeratedly, causing serious adverse effects.

Dosage Forms and Available Strengths:

Ertugliflozin tablets come in two different varieties.

• The pink, triangular, 5 mg (milligrams) pills have the number "701" printed on one side and are plain on the other.

• The red, triangular, 15 mg pills have the number "702" printed on one side and are plain on the other.

For Patients

What Is Type 2 Diabetes Mellitus?

A person with type 2 diabetes has an excessive rise in blood sugar or blood glucose. Blood glucose, the body's primary energy source, is mainly produced by consumed food. The hormone insulin, which the body utilizes to let glucose enter cells for energy, is secreted by the pancreas. But with type 2 diabetes, the body is either unable to use insulin efficiently or fails to create enough of it. Because of this, the bloodstream has too much glucose, and not enough reaches the cells to provide energy.

What Are the Clinical Uses of Ertugliflozin?

SGLT2 (sodium-glucose co-transporter 2) inhibitors, such as Ertugliflozin, help reduce blood sugar levels in treating type 2 diabetes. It is taken with food, exercise, and occasionally additional prescription drugs. Ertugliflozin is not appropriate for diabetic ketoacidosis or type 1 diabetes. Management of diabetes with Ertugliflozin can help avoid consequences such as heart disease, stroke, renal problems, nerve damage, and vision problems. Medication, lifestyle modifications, and routine blood sugar testing are essential. Personalized diabetes care requires communication with healthcare professionals.

How Should Ertugliflozin Be Used?

Ertugliflozin is available as an oral tablet. It is often taken in the morning, with or without meals, once daily. Every day, Ertugliflozin should be taken at around the same time. The patient should carefully read the instructions on the label of their prescription medication, and they should contact their doctor or pharmacist to clarify any information they are unsure of. It is advised that the patient take it precisely as suggested by their physician, neither more nor less.

The patient may be started on a modest dosage of Ertugliflozin and have their dose gradually increased by the doctor.

Type 2 diabetes is only managed by Ertugliflozin and is not cured. Ertugliflozin should be used even if the patient feels good. Ertugliflozin should not be stopped abruptly without first consulting a physician.

What Is the Prescribed Dosage and Method of Administration For Ertugliflozin?

Recommended Dosage:

• In the morning, take 5 mg (milligrams) of Ertugliflozin once daily, with or without meals.

• The dose may be raised to 15 mg once daily if well tolerated for improved blood sugar control.

• Before starting the treatment with Ertugliflozin, patients should have proper volume depletion.

Renal Impairment Patients:

• Before beginning Ertugliflozin and frequently after that, assess kidney function.

• Ertugliflozin should not be used if the estimated glomerular filtration rate (eGFR) is less than 30 mL/minute/1.73 m2 (milliliters per minute per square meter).

• Patients with an eGFR of 30 to less than 60 mL/minute/1.73 m2 should not be put on Ertugliflozin.

• It is not advised to continue using Ertugliflozin if eGFR remains between 30 and less than 60 mL/minute/1.73 m2.

• It is not necessary to alter the dosage for people who have minor renal impairment.

What Are the Side Effects of Ertugliflozin?

The side effects of Ertugliflozin are:

• Increased frequency of urine, especially during the night.

• Tiredness.

• Trouble breathing.

• Red, pink, brown, or hazy urine.

• Vomiting.

• Rectal or pelvic discomfort.

• Rash.

• Reduction in the volume of urine.

• Swelling in the mouth, eyes, tongue, lips, throat, or face.

• Penis rash, pungent discharge from the penis, penis redness, itching, swelling, or pain in the area surrounding the penis.

• Vaginal odor, white or yellowish discharge from the vagina, or vaginal irritation in women.

• Hoarseness.

• Chills, fever, or other infection-related symptoms.

• An increase in thirst.

• Urine with a pungent smell.

• Dry lips.

• Stomach discomfort.

• Urination that is unpleasant, burning, frequent, or urgent.

People must see their physician if they encounter any of these signs.

What Are the Things to Inform the Doctor Before Taking Ertugliflozin?

• Allergies and Medications: The patient should submit a list of all medications, including over-the-counter, prescription, and herbal supplements, and disclose any allergies, particularly about Ertugliflozin.

• Diabetes Medication: The patient should specifically state whether they are using Insulin, oral diabetes drugs, or diuretics, also known as ‘water pills.’ To ensure maximum efficacy, the doctor might need to modify the dosages.

• Kidney Health: The patient should talk to their doctor if they are receiving dialysis or have a history of kidney disease, as Ertugliflozin might not be an appropriate treatment.

• Medical History: The patient should disclose all past medical conditions, including liver disease, pancreatic illness, yeast infections, peripheral vascular disease (a slow and progressive circulation disorder), neuropathy (pain, numbness, and weakness brought on by nerve injury), foot ulcers, low blood pressure, low sodium diet, and amputations.

• Pregnancy and Breastfeeding: The patient should inform the doctor if they are nursing a child or intend to get pregnant shortly. Breastfeeding while taking Ertugliflozin is not advised.

• Surgery and Dental treatments: Patients should inform their doctors that they are taking Ertugliflozin if they have any impending surgeries or dental treatments.

• Alcohol Use: Because alcohol might alter blood sugar levels, the patient should speak with their doctor about the safest way to consume alcohol while taking Ertugliflozin.

• Dizziness and Fainting: Ertugliflozin may induce lightheadedness, dizziness, or fainting. The patient should be aware of this, especially if they rise fast. They should get up from a lying position gradually to lessen this.

• Managing Changes: The patient and physician should talk about what to do in the event of an illness, infection, fever, unexpected stress, or accident. These circumstances may affect blood sugar levels and necessitate changing the dosage of Ertugliflozin.

Dietary Considerations: Make sure to perform the workouts and adhere to the dietitian's or doctor's recommended eating habits. Consuming a nutritious diet is essential. Additionally, pay attention to the doctor's advice and drink lots of water daily while using this medication.

Missed Dose: If the patient forgets to take a dose, they should take it as soon as they remember. However, if their subsequent amount is almost due, they should forgo the missed one and adhere to their regular regimen. Taking only one dose at a time is essential to catch up on missing amounts.

Overdose: Call the poison control hotline for incidences related to overdose. They should be contacted if someone consumes too much of Ertugliflozin and exhibits life-threatening signs such as passing out, experiencing a seizure, having trouble breathing, or not waking up. In case the victim has passed out or is experiencing difficulty breathing, contact emergency assistance immediately.

Storage: Keep the drug out of the reach of children and in its original, tightly sealed container. Keep it away from extreme heat and moisture, and store it at room temperature. Remember that keeping it in the restroom is not recommended.

Disposal: It is essential to dispose of unwanted drugs appropriately to avoid pet or child ingestion. This medicine should never be thrown down the toilet. A pharmaceutical take-back program is the most effective way to eliminate it.

For Doctors

Pharmacodynamics: It was found that the more Ertugliflozin taken by both those in good health and those suffering from type 2 diabetes, the more sugar was detected in their urine. Ertugliflozin at single and multiple dosages both produced this effect. According to the results, Ertugliflozin doses of 5 mg and 15 mg result in nearly the greatest levels of sugar excreted in the urine, and this increased excretion of sugar persists with subsequent doses. The use of Ertugliflozin also increases urine production. When taken at recommended dosages, Ertugliflozin has little effect on the heart's electrical rhythm.

Mechanism of Action: A transporter in the kidneys known as SGLT2 is typically responsible for reintroducing glucose into the circulation from the glomerular filtrate, which acts as a blood filter. Ertugliflozin is a drug that inhibits SGLT2 function. Ertugliflozin inhibits SGLT2, which results in less glucose being reabsorbed into the blood and more glucose ending up in the urine. As a result, more glucose is excreted in urine, and the kidneys' threshold for storing glucose is lowered.

Pharmacokinetics:

• Absorption: Ertugliflozin is absorbed into the bloodstream when taken orally, reaching peak concentrations an hour after consumption. Whether a person has eaten a high-fat, high-calorie meal or is fasting, the absorption process is essentially the same. With varied single and multiple doses, Ertugliflozin exhibits dose-proportional increases in both maximum concentration (Cmax) and total exposure (AUC), suggesting consistent absorption patterns.

• Distribution: The body distributes Ertugliflozin, eventually reaching a steady volume of 85.5 L (liters). The majority of the medication (93.6 percent) binds to plasma proteins. This occurrence is independent of blood Ertugliflozin concentration. This binding remains constant even in patients with compromised liver or kidney function. Ertugliflozin has a blood-to-plasma concentration ratio of 0.66.

• Metabolism: The body's primary process of getting rid of Ertugliflozin is metabolism. Two inactive glucuronide metabolites are produced when the medication is O-glucuronidated by UGT1A9 and UGT2B7. A negligible portion (12 percent) engages in oxidative metabolism mediated by CYP. There is little chance that the body's metabolism of the medication will alter much after taking it repeatedly because this process is comparatively constant over time.

• Excretion: Ertugliflozin is eliminated by the body after metabolism. In people with type 2 diabetes with normal renal function, the estimated elimination half-life is around 16.6 hours, and the mean systemic plasma clearance is 11.2 L/hr (liters per hour). Much of the drug-related radioactivity (40.9 percent in feces and 50.2 percent in urine) is removed after oral delivery. Most of the ejected material is expelled in feces, with only 1.5 percent remaining undisturbed in urine. This excretion pattern points to the breakdown of glucuronide metabolites back into their parent form after biliary excretion.

Drug Interactions:

• Concomitant Administration of Insulin and Insulin Secretagogues: When taken with insulin and an insulin secretagogue, Ertugliflozin may raise the risk of hypoglycemia (low blood sugar). Consequently, a lower insulin dose or an insulin secretagogue may be required when taken with Ertugliflozin to lessen the risk of hypoglycemia.

• Positive Urine Glucose Test: Since SGLT2 inhibitors increase urine glucose excretion and can result in positive urine glucose tests, monitoring glycemic control using urine glucose tests in patients taking these inhibitors is not advised. Modify the way of monitoring the glycemic control.

• Interference Caused by 1,5-Anhydroglucitol Assay: Since measures of 1,5-AG are inaccurate in measuring glycemic control in patients on SGLT2 inhibitors, monitoring glycemic control with this assay is not advised. To keep an eye on glycemic management, use different approaches.

Clinical Studies:

• Efficacy: The most recent SGLT2 inhibitor for type 2 diabetes, Ertugliflozin, shows promise in enhancing glycemic management. It causes weight reduction and lowers blood pressure in eight trials involving 5248 patients. It also reduces HbA1c, postprandial glucose, and fasting plasma glucose.

• Safety: Ertugliflozin's safety is established by the 8246 participants in the VERTIS-CV trial. It does not outperform other SGLT2 inhibitors in lowering severe cardiovascular events, although it has been shown to reduce hospitalizations for heart failure dramatically.

Warnings and Precautions:

• Hypotension: Low blood pressure may be brought on by Ertugliflozin, particularly in elderly or kidney-problematic individuals. Before administering the drug, the physician should assess and adjust the patient's fluid balance. Once the medication is started, watch for any indications of low blood pressure.

• Diabetic Ketosis: Ketoacidosis has been reported in certain Ertugliflozin users, necessitating immediate hospital treatment. Patients with diabetes are more at risk for this. Even if a patient's blood sugar appears normal, they should be evaluated for ketoacidosis if they exhibit severe metabolic problems while taking Ertugliflozin. If there is any suspicion, the medication should be withdrawn, and the patient should receive treatment, perhaps insulin.

• Kidney Problems: Ertugliflozin can impair renal function and cause acute kidney damage. Individuals taking specific drugs or those with pre-existing kidney issues may be particularly vulnerable. Before beginning Ertugliflozin, the doctor should assess renal function; if problems develop, the medicine may need to be discontinued.

• Urinary Tract Infections: Patients on Ertugliflozin have been reported to experience severe urinary tract infections. Urinary tract infections in patients taking this drug should be addressed.

• Risk of Lower Limb Amputation: Research indicates that there may be a chance of lower limb amputation, particularly in people who have had peripheral vascular disease, neuropathy, or diabetic foot ulcers previously. Individuals on Ertugliflozin must closely monitor their lower limb problems and infection symptoms.

• Hypoglycemia With Insulin: Ertugliflozin may raise the risk of low blood sugar when used in conjunction with insulin or specific drugs. To avoid this, the doctor might need to change the insulin dosage.

• Genital Infections: The danger of genital infections is elevated by Ertugliflozin. Individuals who are uncircumcised or have a history of these infections are at a higher risk of contracting them. It is advised to monitor and treat as needed.

• Elevated LDL Cholesterol: Ertugliflozin may cause elevated levels of LDL cholesterol. It is advised to conduct adequate management and routine monitoring.

• Indeterminate Impact on Heart Health: There is insufficient proof to conclude that Ertugliflozin lowers the chance of heart-related problems.

Use in Specific Populations:

• Pregnancy and Fetal Risks: Due to unfavorable effects seen in animal studies, using Ertugliflozin during the second and third trimesters of pregnancy is not advised. There is not enough information available on pregnant women to assess the danger linked with drugs. Both the mother and the fetus are at risk for complications like diabetic ketoacidosis, preeclampsia (hypertension, a condition marked by elevated blood pressure that can happen during pregnancy), spontaneous abortions, preterm delivery, stillbirth, and delivery difficulties when poorly managed diabetes is present during pregnancy.

• Developmental and Lactation Risks: The effects of Ertugliflozin on breastfed infants are unknown, as is its prevalence in human milk. Breastfeeding is not advised due to possible dangers to the developing human kidney as the medication is in the milk of nursing rats. Rats that were nursing and were exposed to Ertugliflozin exhibited hazards to the developing kidney.

• Usage in Children: It is unknown if Ertugliflozin is safe and effective for people under 18.

• Geriatric Considerations: It is not advised to change the dosage by age. On the other hand, volume depletion-related adverse effects may be more common in older patients.

• Disability and Restrictions of the Renal System: Patients with mild renal impairment have not had the safety and effectiveness of Ertugliflozin proven. When treated with Ertugliflozin, patients with moderate renal impairment experienced worsening of their glycemic control and a higher risk of adverse events linked to their kidneys. Patients with end-stage renal disease (ESRD), severe renal impairment, or dialysis recipients are not advised to take the medicine.

• Hepatic Impairment: Dosage modifications are unnecessary for patients with mild to moderate liver impairment. It is not advised for this group of people to use the medication, nevertheless, as it has not been researched in individuals with severe hepatic impairment.