Dapagliflozin offers differences from other SGLT2 inhibitors
Canagliflozin was the first sodium-glucose cotransporter 2 inhibitor to hit the US market in 2013. We now have the second agent in this class, dapagliflozin. I’d like to briefly review some of the data on dapagliflozin and point out a few differences between the two agents.
Henry and colleagues studied use of dapagliflozin (Farxiga, Bristol-Myers Squibb/AstraZeneca), metformin XR or both as initial therapy in patients with type 2 diabetes. Patients were treated with one of these three regimens for 24 weeks. There were about 200 patients in each of the three treatment arms. At the end of the study, HbA1c levels reduced by 2.05% in the dapagliflozin plus metformin XR group vs. a decrease of 1.19% for dapagliflozin alone and 1.35% for metformin XR monotherapy. A second trial of similar design by these researchers yielded similar results, with combination therapy providing statistically significant improvements over either monotherapy treatment arm.
Strojek and colleagues studied the effect of adding dapagliflozin onto existing glimepiride therapy in patients inadequately controlled. More than 850 patients were randomly assigned to one of four treatment arms: addition of placebo, dapagliflozin 2.5 mg, 5 mg or 10 mg to their glimepiride. After 24 weeks, the mean HbA1c reductions for those groups was 0.13%, 0.58%, 0.63%, and 0.82%, respectively.
Nauck and colleagues randomly assigned more than 800 patients inadequately controlled on metformin monotherapy to addition of dapagliflozin or glipizide. Mean HbA1c before randomization was 7.7%, so these patients were near goal. After 52 weeks, the mean HbA1c reduction was identical in both groups (0.52%).
In another trial, Rosenstock and colleagues studied the addition of dapagliflozin or placebo to pioglitazone in nearly 300 patients. After 24 weeks, HbA1c reductions for placebo, dapagliflozin 5 mg and 10 mg were 0.42%, 0.82% and 0.97%, respectively. At 48 weeks, those receiving pioglitazone plus placebo had an average weight gain of 3 kg, whereas those on pioglitazone plus dapagliflozin 5 mg or 10 mg had weight gains of 0.7 kg and 1.4 kg, respectively. Hypoglycemia was rare in all groups. Genital infections were more common in the dapagliflozin groups (8.6-9.2%) vs. placebo (2.9%).
Comparing dapagliflozin and canagliflozin
There are no published head-to-head trials comparing dapagliflozin with canagliflozin (Invokana, Janssen), so we can’t directly compare the two agents. A few differences can be gleaned from the prescribing information. Canagliflozin dosing starts at 100 mg daily but can be increased to 300 mg daily, provided that the patients’ glomerular filtration rate (GFR) is ≥60 mL/minute. If GFR is between 45 mL/minute and 60 mL/minute, the maximum dose is 100 mg daily, and it should be avoided in patients with GFR <45 mL/minute. Dapagliflozin starting dose is 5 mg daily and can be increased to 10 mg, provided GFR is ≥60 mL/minute. It should not be given if GFR is <60 mL/minute. Dapagliflozin should not be given to patients with a history of bladder cancer because, across 22 trials, patients on dapagliflozin had higher rates of newly diagnosed bladder cancer vs. placebo or comparator drugs (0.17% vs. 0.03%). Canagliflozin decreases weight and systolic blood pressure while increasing LDL cholesterol slightly. The effects of dapagliflozin on these parameters is unclear.