Evogliptin

Evogliptin is an Anti-diabetic Agent belonging to the pharmacological class of Dipeptyl peptidase-4 (DPP-4) inhibitors.

Evogliptin is approved for treating type 2 diabetes mellitus. It is used to improve glycemic control by blocking the enzyme DPP-4. It helps control blood sugar levels by enhancing insulin release and reducing glucose production by the liver, thereby improving glycemic control in individuals with type 2 diabetes.

After oral treatment, Evogliptin is absorbed rapidly after oral administration. It reaches peak plasma concentrations (Tmax) within 1 to 2 hours. The drug is primarily metabolised in the liver and has a half-life of approximately 17 to 18 hours. The main route of elimination is through the kidneys, with minimal excretion in faeces.

Hypoglycemia is the most common side effect of Evogliptin. Hypoglycemia can cause lightheadedness, sweating, dizziness, fainting, dry mouth, nausea, and vomiting.

Evogliptin is available in the form of Oral Tablets.

The molecule is available in the United States, South Korea, Canada, the United Kingdom, France, Japan, Germany and Australia.

Evogliptin is an Anti-diabetic Agent belonging to the pharmacological class of Dipeptyl peptidase-4 (DPP-4) inhibitors.

The action of dipeptidyl peptidase-4 (DPP-4) is inhibited explicitly, specifically by evogliptin. This will prevent the breakdown of the hormone GLP-1, which aids in controlling blood sugar levels. The amount of active GLP-1 in the blood increases when DPP-4 is suppressed. This increase in active GLP-1 increases glycemic management and a hypoglycemic impact.

Evogliptin is available in the form of Oral Tablets.

Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.

As the physician recommends, take the medication orally once daily, generally with or without a meal.

Treatment of Type 2 diabetes mellitus

Evogliptin can be used to treat Diabetes mellitus, type 2, treatment. By improving the release of insulin and reducing the quantity of glucose generated by the liver, it helps with blood sugar regulation. Usually, Evogliptin is used along with a healthy diet and regular exercise.

In Treatment of Type 2 diabetes mellitus

Evogliptin helps boost the amount of insulin your body generates following a meal and prevents excessive glucose (sugar) release into the blood. In doing so, it decreases your body's blood glucose levels. It often only causes a single frequent adverse effect and is taken once each day.

To effectively manage diabetes, the blood glucose levels must be reduced. Controlling blood sugar levels will lower the likelihood of any of the severe complications of diabetes, including kidney damage, eye damage, nerve problems, and amputation of limbs. The risk of cardiac disease and stroke can be decreased with proper diabetes management. Individuals can live longer if they take this medication consistently and follow a healthy diet and exercise routine.

It is indicated for the treatment of individuals with type 2 diabetes mellitus. By blocking the enzyme dipeptidyl peptidase-4 (DPP-4), it aids in regulating blood sugar levels by improving the effects of incretin hormones.

Orally: Evogliptin is available as a tablet that can be taken orally. Evogliptin should be taken on an empty stomach or with food. It is best to take it regularly at a fixed time each day following the physician's prescribed schedule for regular and evenly spaced intervals because the dose and duration of therapy are individualised per specific conditions to achieve the most effective and successful treatment outcome.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Tablets: 5mg

Evogliptin is available in the form of Oral Tablets.

Dose Adjustment in Adult Patients:

Regardless of food consumption, oral administration. The maximum daily dose of Evogliptin is 5 mg, the recommended amount as a monotherapy or in combination with metformin.

If one or more doses are missed, the patient should take the medication as soon as they recall. The administration of drugs should continue as normal. A double dose shouldn't be administered on the same day.

Evogliptin should be used in treating Type 2 Diabetes Mellitus, along with appropriate nutritional limits.

While taking Evogliptin, maintain regular meal schedules with balanced macronutrient content to help stabilise blood sugar levels.

Limit or avoid the intake of alcohol as it can interfere with blood sugar regulation.

Avoid high-carbohydrate and sugary foods, such as sugary drinks, sweets, and pastries, should be limited to prevent blood glucose spikes.

It is advised to stay hydrated, maintain a rich, balanced diet low in saturated fats and cholesterol, and consume plenty of vegetables, whole grains, fruits, and lean proteins to help manage your overall health and blood sugar levels effectively.

The dietary restriction should be individualised as per patient requirements.

Evogliptin may be contraindicated in the following conditions:-

• Hypersensitivity reaction to Evogliptin or any of its excipients, including anaphylaxis angioedema.
• Severe ketosis, diabetic coma, pre-coma, and type 1 diabetes.
• Pregnancy and lactation.
• Grade II-IV congestive heart failure (CHF) as per the New York Heart Association (NYHA) classification.

• In case of an allergy to any of the medication's constituents, avoid using evogliptin. Before using this medication, let the physician know if an individual is nursing, planning a pregnancy, or suspects to be pregnant.
• Consult the doctor to know if acute pancreatitis, heart, renal, or other health issues are present.
• Inform the physician of all underlying medical issues before beginning the therapy. Continue to consume the medication until the physician tells you to stop. It is recommended never to give the medication twice to make up for a missed dosage.
• While using Dibasic Calcium Phosphate + Magnesium Orotate, breastfeeding is not suggested.
• Healthcare professionals should use caution and continue diligent patient monitoring while providing Evogliptin to individuals with renal problems. Due to the lack of clinical evidence, it is not recommended to use this drug by people with end-stage renal disease (ESRD) who may require dialysis.
• Before beginning therapy, patients should fully disclose any current medical issues to their doctor. It is essential to avoid double doses if one is missed and to refrain from stopping the medicine until instructed to do so by a healthcare provider. Patients should seek medical advice immediately and speak with their healthcare professional for further information if adverse severe reactions happen.

There is no sufficient scientific evidence traceable regarding the use and safety of Evogliptin with alcohol.

There is no sufficient scientific evidence traceable regarding the use and safety of Evogliptin in breastfeeding.

There is no sufficient scientific evidence traceable regarding the use and safety of Evogliptin in pregnancy.

Limit Alcohol consumption, minimise or avoid sugary drinks or high-carb foods.

The adverse reactions related to Evogliptin can be categorised as:

• Common: Headache, nasopharyngitis (inflammation of the nose and throat)
• Less common: Dizziness, tremor, abdominal pain or discomfort, constipation, diarrhoea, nausea, rash, itching or muscle spasm
• Rare: Pancreatitis (inflammation of the pancreas), hypersensitivity reactions, which may include severe skin reactions, swelling, and breathing difficulties

The clinically relevant drug interactions of Evogliptin are briefly summarised here;-

• Evogliptin exposure can be increased by co-administration with potent CYP3A4 inhibitors like ketoconazole. To avoid dangerously high medication levels, dosage changes can be necessary.
• Strong CYP3A4 inducers, such as rifampin, may lower the body's levels of evogliptin. There may be a need for dosage modifications or other anti-diabetic medications.
• Evogliptin may raise the blood levels of digoxin, which might have hazardous consequences. igoxin may require monitoring and dose changes.
• When used with other medications, warfarin's anticoagulant action may change. It is crucial to check INR (International Normalised Ratio) regularly, and warfarin doses may need to be changed.
• Rifampin may render evogliptin less effective, which could result in hyperglycemia. When co-administering rifampin with an anti-diabetic medication, take other options into account. It is crucial to test blood glucose levels regularly.

The most common side effects of Evogliptin includes-

• Pain in the stomach
• Nasopharyngitis (throat and nasal passageway inflammation)
• Low blood sugar combined with sulphonylurea or insulin is known as hypoglycemia.
• Pain in the joints

• Pregnancy

Pregnancy Category B: Could be acceptable. Either no danger has been shown by animal research, but human studies have yet to be conducted, or some risk has been shown by animal studies but not by human studies.

Evogliptin should not be administered to pregnant women. There have been no controlled, randomised trials on the effectiveness and safety of evogliptin in pregnant women. Evogliptin was found in the bloodstream of a foetus through the placenta, according to the findings of animal experiments.

• Nursing Mothers

Evogliptin excretion in human milk is unknown. Evogliptin was found in a foetus' bloodstream and was secreted in breastfeeding rats' milk. It is not advised to take evogliptin when breastfeeding.

• Pediatric Use

As per FDA, safety and effectiveness in the pediatric population have not been established.

• Geriatric Use

The administration of evogliptin to older people needs to be sufficiently investigated. Elderly individuals typically have impaired hepatic and renal function. Therefore, caution should be given when administering medications, and their health should be closely checked.

Dose Adjustment in Kidney Impairment Patients:

Healthy people are known to eliminate roughly 46.1% of the dosage administered via urine and 42.8% via faeces (including metabolites). Renal function should be managed and care taken during evogliptin administration due to the risk of maintaining the increased level of intact evogliptin in the blood of those patients with moderate and severe renal impairment. It is not advised to administer evogliptin to patients with end-stage renal disease(ESRD) who require dialysis because there is no clinical experience with this approach.

Dose Adjustment in Hepatic Impairment Patients:

There are no specific dosage adjustments provided.

Signs and Symptoms

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Evogliptin.

Overconsumption of Evogliptin could lead to hypoglycemia, including symptoms like sweating, shaking, confusion, dizziness, rapid heartbeat, and, in severe cases, seizures or coma.

Management

There is no specific antidote or treatment for excessive intake of Evogliptin. However, immediate medical attention is essential. Evogliptin should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake.

In severe cases, mainly if the patient is unconscious or having seizures, intravenous glucose or glucagon may be necessary.

If the overdose leads to low blood sugar (hypoglycemia), treatment may involve administering oral glucose or other sources of rapidly absorbed carbohydrates to raise blood sugar levels.

Management typically involves supportive measures like intravenous fluids, electrolyte replacement, and symptomatic treatment such as antiemetic medications for nausea and vomiting.

The patient will continue to be monitored for several hours to ensure that blood sugar levels remain stable and that there are no further complications.

Maintain a healthy lifestyle through proper nutritional diet, regular physical activity, and stress management. These factors can help improve blood sugar control and reduce the risk of hypoglycemia.

Clinical Pharmacology of Evogliptin

Pharmacodynamics:

Dipeptidyl peptidase-4 (DPP-4) is an enzyme that breaks down the incretin hormones and is inhibited by evogliptin from producing its pharmacodynamic effects. Incretins are essential for controlling blood sugar levels, notably glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). Evogliptin extends the duration of these incretins' action by blocking DPP-4. This results in enhanced insulin secretion from pancreatic beta cells and decreased glucagon release from alpha cells, improving glucose-dependent insulin secretion and lowering hepatic glucose generation. Evogliptin may also decrease stomach emptying and improve feeling satiated.

Pharmacokinetics:

Absorption

Evogliptin is quickly absorbed from the digestive system following oral treatment. The normal range for the Tmax, or time to achieve peak plasma concentration, is between one and two hours.

Distribution

Evogliptin is circulated throughout the body by the bloodstream. It has a high protein binding capacity in the plasma and predominantly binds to serum albumin. This binding regulates its retention and dispersion within the circulatory system.

Metabolism

Evogliptin's primary site of metabolism is the liver. Through several chemical modifications, liver enzymes thoroughly metabolise the medication to create metabolites. More often than not, the parent compound's metabolites have lower pharmacological potency. These metabolic activities include the cytochrome P450 enzymes CYP3A4 and CYP3A5.

Excretion

Evogliptin is primarily eliminated by the kidneys, with very little remaining in the faeces. Urine contains both unaltered evogliptin and its metabolites. The medication can be dosed once daily because of its roughly 17–18 hour elimination half-life. The drug's elimination rate is significantly influenced by renal clearance. Therefore, dose changes may be required in patients with impaired renal function.

• Cercato, Cintia et al. "Efficacy and safety of evogliptin in treating type 2 diabetes mellitus in a Brazilian population: a randomised bridging study." Diabetology & metabolic syndrome vol. 11 107. 19 Dec. 2019, doi:10.1186/s13098-019-0505-z
• Chae, Yu-Na et al. "Beneficial Effects of Evogliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, on Adiposity with the Increased Ppargc1a in White Adipose Tissue in Obese Mice." PloS one vol. 10,12 e0144064. 3 Dec. 2015, doi:10.1371/journal.pone.0144064
• Hojin Oh, Hai Duc Nguyen, In Mo Yoon, Min-Sun Kim, Efficacy and Tolerability of Evogliptin in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis with Bayesian Inference Through a Quality-management System, Clinical Therapeutics, Volume 43, Issue 8, 2021, Pages 1336-1355, ISSN 0149-2918, https://doi.org/10.1016/j.clinthera.2021.06.001.
• Park, So-Hee et al. "Cardiovascular safety of evogliptin in the patients with type 2 diabetes: A nationwide cohort study." Diabetes, obesity & metabolism vol. 23,6 (2021): 1232-1241. doi:10.1111/dom.14330
• Tan, Xueying, and Jingbo Hu. "Evogliptin: a new dipeptidyl peptidase inhibitor for treating type 2 diabetes." Expert opinion on pharmacotherapy vol. 17,9 (2016): 1285-93. doi:10.1080/14656566.2016.1183645
• Seo, Songyi et al. "Evogliptin, a dipeptidyl peptidase-4 inhibitor, attenuates pathological retinal angiogenesis by suppressing vascular endothelial growth factor-induced Arf6 activation." Experimental & molecular medicine vol. 52,10 (2020): 1744-1753. doi:10.1038/s12276-020-00512-8

https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety

https://geropharm.com/portfolio/endokrinologiya/evodin-evogliptin

https://www.mrmed.in/molecule/evogliptin