Canagliflozin

Canagliflozin works by blocking SGLT2 (sodium-glucose cotransporter 2) in the kidneys ^{[1, 2]}. SGLT2 normally reabsorbs about 90% of the glucose filtered by the kidneys. By blocking this transporter, canagliflozin causes excess glucose to be excreted in the urine, lowering blood sugar levels independently of insulin ^{[1, 3]}.

At higher doses (300 mg), canagliflozin also partially inhibits SGLT1 in the intestine, which may provide additional postprandial glucose lowering by delaying intestinal glucose absorption ^{[1, 3]}. This dual SGLT2/SGLT1 inhibition at higher doses distinguishes canagliflozin from more selective SGLT2 inhibitors.

Beyond glucose control, canagliflozin has demonstrated significant cardiovascular and kidney benefits ^{[4, 5]}:

Cardiovascular: The CANVAS Program showed canagliflozin reduced the risk of major adverse cardiovascular events (MACE) by 14% — including heart attack, stroke, and cardiovascular death ^[4].

Kidney protection: The CREDENCE trial was the first dedicated kidney outcomes trial for any SGLT2 inhibitor. Canagliflozin reduced the composite endpoint of end-stage kidney disease, doubling of creatinine, or renal/cardiovascular death by 30% ^[5]. The trial was stopped early because the benefit was so clear.

These effects likely result from reduced intraglomerular pressure, mild osmotic diuresis, metabolic improvements, and anti-inflammatory effects ^{[3, 6]}.

The experience starting canagliflozin is similar to other SGLT2 inhibitors ^{[1, 2]}.

First few days: Expect increased urination and mild thirst as the drug promotes glucose and sodium excretion. Stay well hydrated.

First 1-4 weeks: Blood sugar improves gradually. Modest weight loss begins. You may notice mild dizziness if you are also on blood pressure medications or diuretics — the mild diuretic effect of canagliflozin can add to blood pressure lowering.

First 3 months: HbA1c improvement is measurable. Weight loss of 2-4 kg is typical.

Genital hygiene [1]: Like all SGLT2 inhibitors, canagliflozin increases glucose in urine, promoting yeast growth. Maintain good hygiene and treat infections early.

Important — foot care [1, 4]: The CANVAS trial identified an increased risk of lower limb amputations with canagliflozin (primarily toe and metatarsal). While the absolute risk was small and later analyses are reassuring, patients with peripheral vascular disease, neuropathy, prior amputations, or foot ulcers should discuss this risk with their doctor and practice excellent foot care.

Food [1]: Canagliflozin should be taken before the first meal of the day ^[1]. This optimizes SGLT1 inhibition in the intestine (at the 300 mg dose), reducing postprandial glucose absorption.

Alcohol [1]: Alcohol increases dehydration risk and may increase ketoacidosis risk. Limit alcohol consumption, especially excessive intake.

Hydration — IMPORTANT [1, 4]: Adequate fluid intake is essential. Canagliflozin causes glucose and sodium excretion, pulling water into the urine. Drink at least 8 glasses of water daily. Increase during hot weather, exercise, or illness.

Low-carbohydrate diets [1]: Very low-carbohydrate or ketogenic diets may increase DKA risk. Ensure adequate carbohydrate intake (at least moderate) while on canagliflozin.

Type 2 diabetes [1, 2]: - Start: 100 mg once daily before the first meal of the day - May increase to 300 mg once daily for additional glycemic control - Not recommended for initiation if eGFR <30 mL/min/1.73m2 (for glycemic control)

Diabetic kidney disease [1, 5]: - Dose: 100 mg once daily (CREDENCE trial dose) - Approved for patients with eGFR 30-90 mL/min/1.73m2 with albuminuria (UACR >300 mg/g) - Can continue even if eGFR falls below 30 mL/min during treatment

Dose adjustment with UGT inducers [1]: If co-administered with rifampin or other UGT inducers, consider increasing to 300 mg daily in patients currently tolerating 100 mg.

Renal dosing [1]: - eGFR 30-60: Limit to 100 mg daily (for glycemic control) - eGFR <30: Do not initiate for glycemic control. May continue for kidney protection per CREDENCE - Dialysis: Do not use

Pre-surgical: Stop at least 3 days before scheduled surgery to reduce DKA risk ^[1].

Canagliflozin (Invokana) remains brand-name only in the United States as of 2026 ^{[7, 8]}.

Pricing [7, 8]: - Brand Invokana: approximately $500-600/month (list price) - With insurance: $25-150/month depending on plan - Manufacturer savings: eligible patients may pay as little as $0/month

Cost-saving strategies [8]: - Janssen savings program: InvokanaHCP.com — savings cards for commercially insured patients - Patient assistance (Johnson & Johnson PAP): Free medication for qualifying uninsured patients - GoodRx coupons may reduce cash prices - Insurance coverage improving as SGLT2 inhibitor outcome data strengthens

Generic outlook: Generic canagliflozin is not yet available. Generic entry may occur in the coming years as patents expire.

Pregnancy [1]: Canagliflozin is not recommended during pregnancy, particularly in the second and third trimesters. Based on the drug's mechanism (SGLT2 inhibition affecting renal glucose handling) and animal data, canagliflozin may adversely affect kidney development and maturation.

Discontinue canagliflozin when pregnancy is detected ^[1].

Breastfeeding [1, 9]: Canagliflozin is present in rat milk. It is not known whether it is excreted in human breast milk. Due to potential adverse effects on infant kidney development, it is not recommended during breastfeeding ^[1].

As of 2026, canagliflozin is available only as brand Invokana in the United States ^{[7, 8]}.

Available formulations: - Invokana tablets: 100 mg and 300 mg - No generic equivalent available

Combination products: - Invokamet (canagliflozin + metformin IR) - Invokamet XR (canagliflozin + metformin ER)

Comparison to other SGLT2 inhibitors: Canagliflozin is less selective for SGLT2 over SGLT1 compared to empagliflozin and dapagliflozin. At the 300 mg dose, partial SGLT1 inhibition provides additional postprandial glucose lowering but may contribute to diarrhea/GI side effects.