Why Canagliflozin Should Be Taken With Food
Canagliflozin is recommended to be taken with meals primarily to reduce gastrointestinal side effects associated with SGLT2 inhibitors, not because of any significant impact on its pharmacokinetics or efficacy.
Pharmacokinetic Considerations
Research has demonstrated that food has minimal impact on the bioavailability of canagliflozin:
- Studies show that the 90% confidence intervals for canagliflozin's AUC and Cmax when taken with food versus fasting conditions fall entirely within bioequivalence limits (80-125%) 1
- When canagliflozin is administered as part of a fixed-dose combination with metformin, food does not affect canagliflozin's bioavailability parameters 2
Primary Reasons for Taking With Food
1. Reduction of Gastrointestinal Side Effects
- SGLT2 inhibitors, including canagliflozin, can cause gastrointestinal side effects, which may be mitigated by taking the medication with food 3
- When canagliflozin is combined with metformin (as is common in clinical practice), taking it with meals is particularly important to reduce the gastrointestinal intolerability associated with metformin 2
2. Potential Intestinal SGLT1 Inhibition
- Canagliflozin has a modest inhibitory effect on SGLT1 in the intestine at clinical dosages 4
- Taking canagliflozin with food may optimize its ability to delay intestinal glucose absorption through this SGLT1 inhibition mechanism 5
- Research shows canagliflozin reduces postprandial glucose and insulin excursions partly by delaying the rate of appearance of oral glucose in plasma 5
Clinical Management Considerations
When prescribing canagliflozin, healthcare providers should:
- Advise patients to take canagliflozin before the first meal of the day to maximize both its renal SGLT2 inhibition and potential intestinal SGLT1 inhibition effects
- Inform patients that taking the medication with food may help reduce gastrointestinal discomfort
- For patients who are fasting (e.g., during Ramadan), adjust timing to coincide with the main meal of the day 3
Safety Considerations
While not directly related to food intake, important safety considerations when prescribing canagliflozin include:
- Risk of diabetic ketoacidosis (DKA), which requires temporary discontinuation during illness, surgery, or prolonged fasting 3
- Potential for genital mycotic infections, which requires attention to genital hygiene 3
- Risk of volume depletion, especially when used with diuretics 3
- Initial decrease in eGFR that typically stabilizes after continued use 3
By taking canagliflozin with food, patients may experience better tolerability while maintaining the medication's effectiveness in managing diabetes and providing cardiovascular and renal benefits.