Pros and cons
In addition to better diabetes control, there are several other advantages to the use of canagliflozin. The glucose lost in urine by people taking canagliflozin results in a deficit of approximately 200 to 300 calories daily. In clinical trials, people taking canagliflozin lost 2% to 4% of their body weight while taking 300 mg of canagliflozin daily for six months. Another benefit identified in the clinical trials of canagliflozin was that the drug lowered systolic blood pressure between 2 mm Hg and 8 mm Hg.
Low blood glucose episodes (hypoglycemia) appear to be rare in people taking canagliflozin, though the risk does increase when canagliflozin is taken with other drugs that lower blood glucose, such as the sulfonylureas and insulin. The doses of these drugs may need to be decreased if canagliflozin is added and more frequent glucose monitoring may be necessary to avoid hypoglycemia.
Disadvantages of canagliflozin include the lack of long-term efficacy and safety data. Especially lacking are data on canagliflozin’s effect on diabetes complications, including both microvascular complications such as disease of the eyes (retinopathy), the nerves (neuropathy), or the kidneys (nephropathy) and macrovascular complications such as heart attacks and strokes. The FDA did raise concerns about an increased number of cardiovascular events (including heart attacks and strokes) during the first 30 days of one clinical trial. In this trial there were 13 events among the subjects who took canagliflozin, compared to only 1 among those who received a placebo. After the first 30 days of the trial, however, this imbalance equalized, and the FDA decided that it was mainly due to a lower-than-average rate of these events in the placebo group. There was also an increase in LDL cholesterol (low-density lipoprotein, or “bad” cholesterol) of 4% to 8% in clinical trials.
In people who have poor kidney function or who are elderly, canagliflozin may cause a lowering of blood pressure (hypotension) that causes symptoms such as dizziness, light-headedness, and fainting. This is more common in the first few months of use. Others at risk of hypotension are people who are dehydrated or who take certain blood pressure medicines such as diuretics (for example, hydrochlorothiazide or furosemide) or other blood pressure medicines that can affect the kidneys such as ACE inhibitors (lisinopril, ramipril, and others) and ARBs (losartan, valsartan, and others).
High potassium levels in the blood (hyperkalemia) can also occur in people who take canagliflozin if they have kidney problems. This is especially true in people taking drugs that may increase potassium levels (such as potassium-sparing diuretics, which include spironolactone and ACE inhibitors).
The most common adverse effects (occurring in more than 5% of people taking canagliflozin) are related to the genitourinary tract. Vaginal yeast infections occurred in approximately 10% of women who took canagliflozin. More than 5% of study participants also experienced urinary tract infections and increased frequency of urination. Adverse effects that were reported in fewer than 5% of people taking canagliflozin included fungal infections of the penis, vaginal itching, thirst, constipation, nausea, and abdominal pain.
Canagliflozin hasn’t yet been studied in people who have diabetes complications, in pregnant or breast-feeding women, or in children, and canagliflozin should not be used in these populations.