Canagliflozin is an oral antidiabetic drug belonging to the sodium–glucose co-transporter 2 (SGLT2) inhibitor class, used in the treatment of type 2 diabetes mellitus. It lowers blood glucose levels by inhibiting SGLT2 in the proximal renal tubules, thereby reducing glucose reabsorption and promoting urinary glucose excretion in an insulin-independent manner. The concept behind canagliflozin emerged from late 20th-century research on renal glucose transport, which highlighted the key role of SGLT proteins in glucose homeostasis. Developed by Janssen Pharmaceuticals, canagliflozin became the first SGLT2 inhibitor approved by the U.S. FDA in 2013, marking a major advancement in diabetes therapy. Over time, large clinical trials such as CANVAS and CREDENCE demonstrated additional cardiovascular and renal protective benefits, expanding its therapeutic importance beyond glycemic control. Despite certain safety concerns, ongoing research and clinical experience have established canagliflozin as a valuable option in the modern management of type 2 diabetes, especially in patients with cardiovascular and kidney disease.
BRAND NAMES
• Invokana
• Invokamet (combination with metformin)
• Sulisent (less common, in some markets)
MECHANISM OF ACTION
Canagliflozin works by blocking SGLT2 proteins in the kidneys, preventing glucose from being reabsorbed into the blood. This causes excess sugar to be excreted in the urine, lowering blood glucose levels. It also helps with mild weight loss and can slightly reduce blood pressure.
PHARMACOKINETICS
Absorption
Canagliflozin is rapidly absorbed after oral administration, with peak blood levels occurring about 1–2 hours after taking a dose. Its oral bioavailability is approximately 65%, and absorption is slightly reduced when taken with a high-fat meal, though this does not significantly affect its overall effectiveness.
Distribution
• Volume of distribution (Vd): approximately 119 liters
• Plasma protein binding: about 99%, mainly to albumin
Metabolism
Canagliflozin is mainly metabolized in the liver by UGT enzymes into inactive metabolites. Only a small amount is processed by CYP3A4, and most of the drug is eliminated in urine and feces.
Excretion
Canagliflozin is excreted mostly in the urine and feces as inactive metabolites. Only a small portion of the drug is eliminated unchanged in the urine. Its half-life is about 10–13 hours, allowing once-daily dosing.
PHARMACODYNAMICS
Canagliflozin lowers blood sugar by blocking kidney SGLT2, causing excess glucose to be excreted in urine. It also helps with mild weight loss and lowers blood pressure slightly.
DOSAGE AND ADMINISTRATION
• Typical starting dose: 100 mg orally once daily, taken before the first meal of the day.
• Maximum dose: 300 mg once daily, if needed and tolerated.
CONTRAINDICATIONS
• Patients with severe kidney impairment or on dialysis
• Individuals with a history of serious hypersensitivity to canagliflozin
• Patients with type 1 diabetes (risk of ketoacidosis)
DRUG INTERACTIONS
• Diuretics – can increase risk of dehydration and low blood pressure
• Insulin or other antidiabetic drugs – may increase risk of low blood sugar (hypoglycaemia)
• Rifampin, phenytoin, or ritonavir – can reduce canagliflozin levels by inducing liver enzymes
FOOD INTERACTIONS
Canagliflozin can be taken with or without food, as food does not significantly affect its overall absorption or effectiveness. However, taking it before the first meal of the day is recommended to maximize its blood sugar-lowering effect.
SIDE EFFECTS
• Genital yeast infections (more common in women)
• Urinary tract infections
• Increased urination
• Thirst or dehydration
• Low blood pressure (hypotension)
OVER DOSE
An overdose of canagliflozin may cause dehydration, low blood pressure, or low blood sugar. Treatment involves supportive care and monitoring.
TOXICITY
Canagliflozin toxicity can cause dehydration, low blood pressure, kidney problems, and rarely ketoacidosis. Treatment is supportive care and monitoring.
