New Drugs and Therapeutics Update: INVOKANA® (canagliflozin)
Prepared by Preneet Cheema Brar, MD, MS and Daniel Mak, MD.
INVOKANA® (canagliflozin)
In December 2024, the FDA approved INVOKANA® (canagliflozin) for the treatment of type 2 diabetes mellitus (T2DM) in pediatric patients ages 10 years and older. INVOKANA® is an oral sodium-glucose co-transporter 2 (SGLT2) inhibitor that lowers blood glucose levels by reducing renal glucose reabsorption, leading to increased urinary glucose excretion.
The approval was based on a Phase 3, 52-week double blind, placebo-controlled, parallel-group trial (NCT03170518) that enrolled 171 pediatric patients (ages 10-17 years) with T2DM (HbA1C ≥6.5% and ≤11.0%). Participants were randomized to INVOKANA® (100mg, n=84) or placebo (n=87) as adjunct to diet and exercise alone (14%), metformin HCl monotherapy (≥1,000 mg per day or maximally tolerated dosage; 46%), insulin monotherapy (11%), or a combination of metformin HCl and insulin (29%). Patients with an eGFR < 60 mL/min/1.73 m2 were excluded from the trial, and no enrolled participants experienced a decline below this threshold.
At Week 13, patients in the INVOKANA® group with HbA1C ≥7.0% were re-randomized to either continue INVOKANA® 100 mg orally once daily (n=16) or increase to 300 mg once daily (n=17). Data were pooled and analyzed for the combined population of arm INVOKANA®100 mg and INVOKANA®300 mg. By Week 26, INVOKANA® demonstrated a statistically significant improvement in HbA1C compared to placebo. The mean change from baseline in HbA1c was -0.38% with INVOKANA® vs +0.34% with placebo, while the change in fasting plasma glucose was -8.22 mg/dL vs. +17.29 mg/dL with placebo.1,2
Dosage and administration
INVOKANA® is available in tablets in two strengths 100 and 300 mg and is approved for 10 years and older with type 2 diabetes mellitus, with a starting dose of 100 mg orally once daily, taken before the first meal of the day to improve glycemic control.
For patients requiring additional glycemic control, the dosage can be increased to 300 mg once daily if they are tolerating the 100 mg once daily dose and have an eGFR of 60 mL/min/1.73 m2 or greater. For GFR 30-60 eGFR (mL/min/1.73 m2), the maximum dose should be 100 mg and it should not be used at eGFR less than 30 mL/min/1.73 m2.
Adverse effects: The most serious adverse effect of INVOKANA® is an increased risk for diabetic ketoacidosis (including nausea, vomiting, abdominal pain, tiredness, and labored breathing) especially when used off-label in Type 1 diabetes and in those with a history of pancreatitis and pancreatic surgery. If symptoms are observed, patients should be advised to check for ketones even if they have euglycemia, and they should seek immediate medical attention. Patients should be counseled about signs/symptoms of UTIs (as increased risk has been reported); and hypoglycemia when used concomitantly with insulin or insulin secretagogues. Other reported adverse effects in adults include gangrene, vulvovaginitis, and mycotic infections.
This approval expands treatment options for pediatric patients with T2DM, offering an oral, non-insulin-based approach to improve glycemic control.
References:
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/204042s043lbl.pdf
2.https://clinicaltrials.gov/study/NCT03170518?term=pediatric&intr=invokana&rank=1&tab=results#outcome-measures