Tofogliflozin is an oral antidiabetic drug belonging to the class of sodium-glucose co-transporter 2 (SGLT2) inhibitors. It is primarily used for the management of type 2 diabetes mellitus by promoting the excretion of excess glucose through the urine. Developed and marketed mainly in Japan, tofogliflozin offers glycemic control with additional benefits such as weight loss and blood pressure reduction. Tofogliflozin was approved in Japan in March 2014 for the treatment of type 2 diabetes mellitus and is marketed under brand names such as Apleway and Deberza, has not received regulatory approval for use in the United States, Europe, or India, and therefore is not available for clinical use or commercial distribution in these regions.
BRAND NAMES
Apleway: Apleway is a 20 mg oral tablet formulation of tofogliflozin, an SGLT2 inhibitor used for the treatment of type 2 diabetes mellitus. It works by enhancing urinary glucose excretion, thereby lowering blood glucose levels, and is administered once daily.
Deberza: Deberza is a 20 mg oral tablet of tofogliflozin marketed by Kowa in Japan. It is taken once daily, either before or after breakfast, to manage type 2 diabetes by promoting the excretion of glucose through urine.
MECHANISM OF ACTION
Tofogliflozin is an antidiabetic agent that exerts its effect by selectively inhibiting the sodium-glucose co-transporter 2 (SGLT2) located in the proximal convoluted tubules of the kidneys. Under normal physiological conditions, around 90% of the filtered glucose is reabsorbed into the bloodstream through the action of SGLT2 in the kidneys. By blocking this transporter, tofogliflozin significantly reduces glucose reabsorption, leading to an increase in urinary glucose excretion (glucosuria). This mechanism results in a reduction in both fasting and postprandial blood glucose levels, independent of insulin secretion or action. Additionally, the loss of glucose through urine contributes to a mild calorie deficit, which may support weight loss, and its osmotic diuretic effect can help in lowering blood pressure. This unique mode of action makes tofogliflozin an effective treatment option for patients with type 2 diabetes, especially those who are overweight or have insulin resistance.
PHARMACOKINETICS
Absorption
Tofogliflozin is rapidly absorbed after oral administration, with peak plasma concentrations typically reached within 1 to 2 hours, and its absorption is not significantly affected by food intake.
Distribution
Tofogliflozin exhibits a moderate volume of distribution and is highly bound to plasma proteins, with more than 99% of the drug primarily bound to albumin.
Metabolism
Tofogliflozin is primarily metabolized in the liver through glucuronidation, mainly by the enzyme UGT1A9, with minimal involvement of cytochrome P450 enzymes, indicating a low potential for CYP-mediated drug interactions.
Elimination
Tofogliflozin has an elimination half-life of around 5 to 6 hours and is cleared from the body through both renal and fecal routes, with approximately 30–40% excreted in the urine primarily as metabolites, and about 60–70% eliminated in the feces, mainly as the unchanged drug along with its metabolites.
PHARMACOGYNAMICS
Tofogliflozin is a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor that lowers blood glucose levels by reducing renal glucose reabsorption and increasing urinary glucose excretion. Its effect is dose-dependent and independent of insulin secretion, making it effective even in patients with insulin resistance or β-cell dysfunction. By promoting glucosuria, it also contributes to a modest reduction in body weight and systolic blood pressure. The drug selectively targets SGLT2 over SGLT1, minimizing gastrointestinal side effects and enhancing safety. The glucose-lowering effect typically begins within hours of dosing and is sustained with once-daily administration.
DOSAGE AND ADMINISTRATION
Tofogliflozin is administered orally at a recommended dose of 20 mg once daily for the treatment of type 2 diabetes mellitus. It can be taken either before or after breakfast and does not require food for optimal absorption, making it convenient for patients to incorporate into their daily routine. Dose adjustments are generally not necessary in patients with mild to moderate renal or hepatic impairment; however, it is not recommended for use in individuals with severe renal dysfunction or end-stage renal disease due to reduced efficacy and potential safety concerns.
DRUG INTERACTIONS
- Furosemide: Increases risk of dehydration and low blood pressure.
- Amlodipine: May cause additive hypotensive effects.
- Glimepiride: Raises the risk of hypoglycemia.
- Ibuprofen: May impair kidney function when used together.
- Digoxin: Tofogliflozin may slightly increase digoxin levels.
- Rifampicin: Can reduce the effectiveness of tofogliflozin.
CONTRAINDICATIONS
- Severe renal impairment or ESRD: Contraindicated due to reduced efficacy and higher risk of adverse effects.
- Hypersensitivity: Should not be used in patients allergic to tofogliflozin or its ingredients.
- History of diabetic ketoacidosis (DKA): Not recommended as it may increase the risk of DKA.
- Pregnancy and lactation: Use is contraindicated due to potential risks to the fetus or nursing infant.
- Type 1 diabetes mellitus: Not indicated as it may raise the risk of ketoacidosis.
SIDE EFFECTS
Common side effects of tofogliflozin:
- Urinary tract and genital infections
- Increased urination
- Dehydration and thirst
- Constipation
- Low blood pressure
- Risk of ketoacidosis
- Low blood sugar (with insulin/sulfonylureas)
- Possible kidney issues
- Slight increase in LDL cholesterol
TOXICITY
Tofogliflozin toxicity mainly results from its diuretic effect, causing dehydration and low blood pressure. It increases the risk of urinary and genital infections due to glucose in the urine. Rarely, it may lead to serious conditions like euglycemic diabetic ketoacidosis. Renal impairment can occur, especially in patients with existing kidney issues.
