Can triple-therapy be as safe as using just two medications in type 2 diabetes?

This study compared the safety of using three different medications to treat type 2 diabetes (T2D) with using only two of those medications. It was determined that using three medications was as safe as using two.

Control of blood glucose levels is important to prevent the long-term complications of T2D. Metformin (Glucophage) is the first drug given to most people with T2D. Eventually, many people will need more than one drug to control blood glucose levels. Adding a second or third drug can be more effective, but may also increase the risk of side effects.

Dapagliflozin (Farxiga) is an SGLT2 inhibitor.  SGLT2 inhibitors prevent glucose from re-entering the bloodstream from the kidneys. Saxagliptin (Onglyza) is a DPP4 inhibitor. DPP4 inhibitors help to stimulate the release of insulin (the hormone that lowers blood glucose) and inhibit the release of glucagon (hormone that raises blood glucose). Whether the combination of dapagliflozin and saxagliptin is safe for use with metformin is still under investigation.

This study examined data from 3 different studies, including 1169 adults with T2D. In each study, patients were randomly divided into 3 groups. Group 1 received dapagliflozin and metformin. Group 2 received saxagliptin and metformin. Group 3 received all 3 medications. They were followed for 24 weeks.

Side effects occurred at similar rates in all groups. 46% of group 1 experienced any side effect, compared with 55.7% of group 2, and 50.8% of group 3. Side effects related to the medications occurred in 6.2% of group 1, 6.8% of group 2, and 6.5% of group 3. Serious side effects occurred in 2.1% of group 1, 2.7% of group 2, and 2.4% of group 3. Less than 2% of participants in any group experienced hypoglycemia (dangerously low blood glucose levels). Urinary tract infections (UTIs) occurred at a similar rate in all groups.

Some participants in group 3 were given dapagliflozin and saxagliptin at the same time (concomitant add-on), while others received one after the other (sequential add-on). Side effects occurred in 48.6% of those who received concomitant add-on, and 52.1% of those with sequential add-on. UTIs were more common in those with sequential (5.1%) than with concomitant (0.6%) add-on.

The study concluded that it is as safe to use both dapagliflozin and saxagliptin in addition to metformin as it is to use either on its own with metformin.

People with poor kidney function, cardiovascular disease, and high blood pressure were not included in these studies. Thus the results may not apply to all people with T2D. Additionally, this study was funded by the manufacturers of saxagliptin and dapagliflozin.