At a late-breaking session of the American Association of Clinical Endocrinologists meeting, William Canovatchel, MD, Janssen Pharmaceuticals, presented data showing that in a phase III study, patients had significantly greater reductions in HbA1c with either of two doses of canagliflozin compared with those on placebo (P<0.001 for both).
Canagliflozin has been shown in several studies to reduce HbA1c, body weight, and blood pressure, and has been generally used as an add-on therapy when patients fail other antihyperglycemic agents such as metformin.
To assess its efficacy as monotherapy in patients whose type 2 diabetes isn't controlled with diet and exercise alone, Canovatchel and colleagues enrolled 584 patients in a 26-week trial.
They were randomized to placebo or to one of two doses of canagliflozin (100 mg or 300 mg) and the primary endpoint was change in HbA1c. The secondary endpoint was change in body weight from baseline.
Overall, the researchers found significantly higher reductions in HbA1c with both doses of the drug compared with placebo:
- 100 mg: -0.91% (P<0.001)
- 300 mg: -1.16% (P<0.001)
They also saw a significantly greater change in body weight in both drug groups compared with placebo:
- 100 mg: -2.2%, -1.9 kg (P<0.001)
- 300 mg: -3.3%, -2.9 kg (P<0.001)
For the composite endpoint of A1c and body weight taken together, the researchers found that more than 70% of patients treated with the 100-mg dose and 80% of those in the 300-mg group had a reduction in both A1c and body weight compared with only 28% of those on placebo.
In terms of safety, there were similar proportions of adverse events across all three groups, in about 53% of those on placebo, 61% of those on the 100-mg dose, and 60% of those in the 300-mg group.
The well-established side effect of genital mycotic infections was also seen in this trial, with 2.5% of men in the 100-mg dose and 5.6% of men in the 300-mg group experiencing such infections compared with none of the men on placebo. For women in the placebo group, only 3.8% had infections compared with 8.8% of those on the 100-mg dose and 7.4% of those in the 300-mg group. There was no significant increase in hypoglycemia with the drug, occurring in 2.6% of those on placebo, 3.6% of those in the 100-mg group, and 3% of those in the 300-mg group.
Canovatchel concluded that for type 2 diabetes patients who failed diet and exercise, canagliflozin is associated with significant reductions in both HbA1c and body weight compared with placebo -- and that the findings suggest the SGLT2-inhibitor may be an effective monotherapy, which "may impact the selection of therapeutics for type 2 diabetes management."
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Overall, the researchers found significantly higher reductions in HbA1c with both doses of the drug compared with placebo
AACE- Source reference: Canovatchel W, et al "Canagliflozin monotherapy provides reductions in a composite measure of A1c and body weight in patients with type 2 diabetes mellitus" AACE 2014.