Canagliflozin (Invokana) for type 2 diabetes is an oral medication that helps control blood glucose levels through a unique mechanism: it works via the kidneys to remove excess glucose through urine. As a sodium-glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin offers benefits beyond glucose control, including cardiovascular and kidney protection, making it particularly valuable for patients with established heart disease or diabetic kidney disease. Approved by the MHRA in 2013, it has become an established treatment option within UK diabetes care, typically used alongside metformin or when metformin alone is insufficient. Understanding how canagliflozin works, who benefits most, and what safety considerations apply is essential for effective type 2 diabetes management.

What Is Canagliflozin (Invokana) and How Does It Work?

Canagliflozin, marketed under the brand name Invokana, is an oral antidiabetic medication licensed in the UK for the treatment of type 2 diabetes mellitus. It belongs to a class of drugs known as sodium-glucose co-transporter 2 (SGLT2) inhibitors, which represent a relatively modern approach to glucose management that works independently of insulin secretion or sensitivity.

The mechanism of action centres on the kidneys' role in glucose regulation. Under normal circumstances, the kidneys filter glucose from the blood, but SGLT2 proteins in the proximal tubules reabsorb nearly all of this glucose back into the bloodstream. Canagliflozin selectively inhibits these SGLT2 transporters, thereby reducing glucose reabsorption and promoting urinary glucose excretion. This process results in the elimination of glucose through urine—the amount varies with kidney function and baseline blood glucose levels—which translates to a reduction in blood glucose levels without stimulating insulin release.

Beyond glycaemic control, canagliflozin offers additional metabolic benefits. The urinary glucose loss creates a caloric deficit, often leading to modest weight reduction—an advantage for many patients with type 2 diabetes who struggle with obesity. Furthermore, clinical trials (including CANVAS and CREDENCE) have demonstrated cardiovascular and renal protective effects, with evidence suggesting reduced risk of major adverse cardiovascular events and slowed progression of diabetic kidney disease. In the UK, canagliflozin is licensed not only for glycaemic control but also, at a dose of 100 mg once daily, for reducing the risk of cardiovascular events in adults with type 2 diabetes and established cardiovascular disease, and for the treatment of adults with type 2 diabetes and diabetic kidney disease (albuminuria). The Medicines and Healthcare products Regulatory Agency (MHRA) approved canagliflozin in 2013, and it has since become an established option within the UK's diabetes treatment landscape, particularly for patients requiring additional glycaemic control or those with established cardiovascular disease or chronic kidney disease.

Using Canagliflozin for Type 2 Diabetes Management

Canagliflozin is indicated for adults with type 2 diabetes mellitus and can be prescribed in several clinical scenarios. According to NICE guidance NG28 (Type 2 diabetes in adults: management), SGLT2 inhibitors like canagliflozin may be considered when metformin is contraindicated or not tolerated, or as add-on therapy when metformin alone provides insufficient glycaemic control. It can be used in combination with other antidiabetic agents, including metformin, sulfonylureas, insulin, or dipeptidyl peptidase-4 (DPP-4) inhibitors.

The decision to initiate canagliflozin should be individualised, taking into account the patient's HbA1c levels, cardiovascular risk profile, renal function, and treatment goals. NICE NG28 recommends offering an SGLT2 inhibitor with proven cardiovascular benefit (such as canagliflozin) to adults with type 2 diabetes who have established atherosclerotic cardiovascular disease or who are at high cardiovascular risk. NICE NG203 (Chronic kidney disease: assessment and management) recommends offering an SGLT2 inhibitor with proven benefit to adults with type 2 diabetes and chronic kidney disease if they have an estimated glomerular filtration rate (eGFR) of 25–75 mL/min/1.73m² and a urine albumin-to-creatinine ratio (ACR) of 3 mg/mmol or more, given the demonstrated renal and cardiovascular benefits in this population.

Patients typically experience a gradual reduction in HbA1c of approximately 0.5–1.0% when canagliflozin is added to existing therapy. The glucose-lowering effect becomes apparent within days to weeks, though maximum benefit may take several months. It is important to note that canagliflozin's glucose-lowering efficacy depends on adequate kidney function (glomerular filtration), as its mechanism requires functioning nephrons to filter and excrete glucose.

Regular monitoring is essential during treatment. Baseline assessments should include renal function (eGFR), electrolytes, blood pressure, and foot examination. HbA1c should be reviewed every 3–6 months initially, with ongoing monitoring of renal function at least annually or more frequently in patients with existing kidney impairment. Healthcare professionals should also assess for volume depletion, particularly in elderly patients or those taking diuretics. Patients should be educated on sick-day rules: during intercurrent illness, dehydration, or fasting, they should check blood ketone levels if unwell and consider temporarily stopping canagliflozin after discussion with their GP or diabetes team. If symptoms of diabetic ketoacidosis (DKA) develop—such as nausea, vomiting, abdominal pain, excessive thirst, difficulty breathing, confusion, or unusual fatigue—patients must seek urgent same-day medical assessment; if severely unwell, they should attend A&E or call 999 immediately.

Dosage, Administration and Treatment Guidelines

Canagliflozin is available in the UK as 100 mg and 300 mg film-coated tablets. The recommended starting dose for most patients is 100 mg once daily, taken before the first meal of the day. This timing optimises the drug's effect on postprandial glucose excretion, though the medication remains effective regardless of food intake.

For patients who require additional glycaemic control and tolerate the initial dose well, the dose may be increased to 300 mg once daily after assessing renal function and clinical response. However, dose escalation must be carefully considered in light of kidney function. According to the UK Summary of Product Characteristics (SmPC), the 300 mg dose should only be used in patients with an eGFR of 60 mL/min/1.73m² or above. For those with moderate renal impairment (eGFR 45 to less than 60 mL/min/1.73m²), the dose should be limited to 100 mg once daily.

For glycaemic control, canagliflozin should not be initiated in patients with eGFR below 60 mL/min/1.73m². In patients already receiving canagliflozin whose eGFR falls persistently below 45 mL/min/1.73m², the dose should be adjusted to or maintained at 100 mg once daily. If eGFR falls persistently below 30 mL/min/1.73m², canagliflozin should be discontinued. However, for patients with type 2 diabetes and diabetic kidney disease (albuminuria), canagliflozin 100 mg may be initiated if eGFR is 30 mL/min/1.73m² or greater, primarily for renal and cardiovascular protection. Canagliflozin is contraindicated in patients with end-stage renal disease or on dialysis, as the drug's mechanism requires functioning nephrons.

Perioperative management is important: canagliflozin should be stopped 3 days before elective major surgery or procedures requiring prolonged fasting or reduced fluid intake, due to the increased risk of volume depletion and ketoacidosis. Treatment may be restarted once the patient is eating and drinking normally and blood ketone levels are normal. Treatment should also be interrupted temporarily during periods of acute illness, severe dehydration, or gastrointestinal upset. Patients should be advised to maintain adequate hydration, particularly during hot weather or when experiencing illness.

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next dose—patients should not double up doses. Healthcare professionals should provide clear written and verbal instructions regarding administration, and pharmacists play a vital role in reinforcing these messages during dispensing.

Side Effects and Safety Considerations

Like all medications, canagliflozin can cause side effects, though not everyone experiences them. Understanding the adverse effect profile is crucial for both prescribers and patients to ensure safe, effective use.

Common side effects (affecting up to 1 in 10 people) include:

• Genital and urinary tract infections: The increased glucose in urine creates a favourable environment for fungal and bacterial growth. Vulvovaginal candidiasis in women and balanitis in men are particularly common. Most cases respond well to standard antifungal treatments and do not require discontinuation of canagliflozin.

• Increased urination (polyuria): The osmotic diuretic effect of urinary glucose excretion leads to increased urine volume, particularly noticeable in the first weeks of treatment.

• Thirst and dehydration: Related to fluid loss, especially in elderly patients or those taking loop diuretics.

• Hypoglycaemia: When used alone, canagliflozin carries minimal hypoglycaemia risk. However, when combined with insulin or sulfonylureas, the risk increases, and dose adjustments of these agents may be necessary.

Serious but less common adverse effects require particular vigilance:

• Diabetic ketoacidosis (DKA): A rare but serious complication that can occur even with near-normal blood glucose levels ('euglycaemic DKA'). The MHRA has issued safety warnings regarding this risk. Patients should be educated to recognise symptoms including nausea, vomiting, abdominal pain, excessive thirst, difficulty breathing, confusion, and unusual fatigue. If DKA is suspected, treatment must be stopped immediately and urgent medical assessment sought. If severely unwell, patients should attend A&E or call 999.

• Fournier's gangrene (necrotising fasciitis of the perineum): This is a rare but life-threatening infection of the genital or perineal area requiring emergency medical attention. Symptoms include genital or perineal pain, tenderness, redness, swelling, or fever. Patients experiencing these symptoms should seek immediate medical help by attending A&E or calling 999.

• Lower limb amputations: The CANVAS trial identified an increased risk of lower limb amputations, predominantly affecting toes. The MHRA advises that patients with peripheral vascular disease, previous amputation, neuropathy, or diabetic foot ulcers require careful assessment before initiation, regular foot examinations during treatment, and optimised preventive foot care. Canagliflozin should be discontinued if significant foot complications (such as infection, ulcers, or gangrene) develop.

• Bone fractures: Clinical trial data suggest a possible increased risk of bone fractures with canagliflozin, particularly in the first year of treatment. Patients at higher fracture risk should be assessed and monitored accordingly.

• Acute kidney injury (AKI): Volume depletion and hypotension may precipitate AKI, particularly in elderly patients, those with existing renal impairment, or patients taking diuretics or ACE inhibitors/ARBs. Monitoring of volume status and renal function is essential.

• Volume depletion and hypotension: Particularly in elderly patients, those with impaired renal function, or patients taking antihypertensive medications.

Patients should contact their GP or diabetes team if they experience:

• Signs of genital or urinary infection that do not improve with standard treatment

• Symptoms suggestive of DKA (seek urgent same-day assessment; attend A&E or call 999 if severely unwell)

• Symptoms of Fournier's gangrene (attend A&E or call 999 immediately)

• Persistent dizziness or fainting

• New foot pain, ulcers, or infections

• Severe dehydration or inability to maintain fluid intake

Reporting side effects: Patients and healthcare professionals are encouraged to report any suspected side effects via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or through the Yellow Card app. Reporting helps monitor the safety of medicines.

Regular monitoring and patient education significantly reduce the risk of serious complications whilst allowing most patients to benefit from canagliflozin's therapeutic effects.

Who Should Not Take Canagliflozin

Canagliflozin is not suitable for everyone, and several absolute and relative contraindications must be considered before prescribing.

Absolute contraindications include:

• Type 1 diabetes mellitus: Canagliflozin is not licensed for type 1 diabetes and must not be used as a substitute for insulin in these patients. The increased risk of diabetic ketoacidosis makes its use particularly hazardous in this population.

• Hypersensitivity: Patients with known hypersensitivity to canagliflozin or any excipients should not receive this medication. Allergic reactions, though rare, can include rash, urticaria, or more severe reactions.

• End-stage renal disease or dialysis: Canagliflozin is contraindicated in patients with end-stage renal disease or on dialysis, as the drug's mechanism requires functioning nephrons and is ineffective in these patients.

• Children and adolescents under 18 years: Canagliflozin is not recommended in patients under 18 years of age due to lack of data on safety and efficacy in this population.

Situations where canagliflozin should not be initiated or requires caution:

• Renal impairment: For glycaemic control, canagliflozin should not be initiated if eGFR is below 60 mL/min/1.73m². For patients with diabetic kidney disease (albuminuria), initiation at 100 mg may be considered if eGFR is 30 mL/min/1.73m² or greater, under specialist guidance. Treatment should be discontinued if eGFR falls persistently below 30 mL/min/1.73m².

• Severe hepatic impairment: Canagliflozin is not recommended in patients with severe hepatic impairment due to limited clinical experience. No dose adjustment is required for mild to moderate hepatic impairment.

• Elderly patients (≥75 years): Increased risk of volume depletion, hypotension, and renal impairment necessitates careful monitoring. Dose escalation to 300 mg should be undertaken cautiously, if at all, in this age group due to increased risk of adverse effects.

• History of lower limb amputation or peripheral vascular disease: The increased amputation risk identified in clinical trials means these patients require thorough risk-benefit assessment, enhanced preventive foot care, and regular foot examinations. Canagliflozin should be discontinued if significant foot complications develop.

• Recurrent genital infections: Patients with frequent candidal infections may find these worsen with canagliflozin.

• Pregnancy and breastfeeding: Canagliflozin is not recommended during pregnancy or breastfeeding due to insufficient safety data. Women of childbearing potential should use effective contraception, and alternative diabetes treatments should be considered when planning pregnancy or if pregnancy occurs.

• Patients at risk of diabetic ketoacidosis: Those with low insulin reserve (e.g., due to pancreatic disease or previous pancreatitis), reduced caloric intake, acute illness, dehydration, or recent insulin dose reduction require careful consideration and close monitoring.

• Patients at increased risk of fractures: Those with osteoporosis or other risk factors for fracture should be assessed and monitored, given the possible increased fracture risk observed in clinical trials.

Before initiating canagliflozin, prescribers should conduct a comprehensive assessment including medical history, current medications, renal function, cardiovascular risk, and foot examination. Shared decision-making, incorporating patient preferences and individual risk factors, ensures appropriate patient selection and optimises treatment outcomes whilst minimising potential harms.

Frequently Asked Questions