Take two or take three? Adding saxagliptin and dapagliflozin to metformin

This study explored the effectiveness and safety of adding two glucose-lowering drugs, saxagliptin (Onglyza) and dapagliflozin (Farxiga), to patients with type 2 diabetes uncontrolled by metformin (Glucophage) alone.

Type 2 diabetes is a progressive disease. While some patients may initially be able to control their blood glucose (sugar) levels with diet and exercise, eventually glucose-lowering medications must be added. Metformin is generally the first glucose-lowering drug tried. Metformin increases the body’s sensitivity to insulin, the hormone needed to break down the glucose taken in from food. If metformin treatment does not control blood glucose levels, other therapies must be added. However, there is no definite guideline for deciding which treatment to use in combination with metformin.

Dapagliflozin is a treatment that increases the amount of glucose excreted through the urine, decreasing levels in the blood. Saxagliptin is a treatment that increases the amount of insulin produced by the body. Because dapagliflozin and saxagliptin help to control blood glucose in different ways, it may be more beneficial to use both in combination with metformin, rather than either alone.

In the current study, 534 type 2 diabetes patients were randomly assigned to one of three groups: Group 1 received dapagliflozin, saxagliptin, and metformin (179 patients); Group 2 received saxagliptin and metformin (176 patients); and Group 3 received dapagliflozin and metformin (179 patients). HbA1c levels, fasting glucose levels (blood glucose level after a period without food or drink), and weight at the end of 24 weeks were compared to those at the beginning of the study.

HbA1c levels decreased significantly more in the patients in Group 1 (1.47%) compared to those in Group 2 (0.88%) or Group 3 (1.20%). The decrease in HbA1c was highest for those patients who had HbA1c levels higher than 9% at the start of the study. In these patients, those in Group 1 saw a decrease of 2.03%, those in Group 2 decreased by 1.32%, and those in Group 3 decreased by 1.87%. 41% of Group 1 patients achieved HbA1c levels of less than 7%, compared to 18% in Group 2 and 22% in Group 3.

Fasting blood glucose decreased significantly more in patients in Group 1 (decrease of 38 mg/dL) compared to those in Group 2 (decrease of 14 mg/dL), but were not significantly different from those in Group 3 (decrease of 32 mg/dL). Patients in Group 1 lost an average of 2.1 kg, and patients in Group 3 an average of 2.4 kg. No weight change was seen in Group 2.

Adverse events (negative side effects) were similar across the groups. Urinary tract infections were more common in Group 2 (5%) and Group 3 (4%) than in Group 1 (0.6%). Genital infections were more common in Group 3 (6%) than in the other two groups (0 in group 1 and 0.6% in group 2).

This study concluded that adding both dapagliflozin and saxagliptin to metformin therapy led to greater improvements in blood glucose control than did metformin use with the addition of dapagliflozin or saxagliptin alone.

This study was funded by AstraZeneca and Bristol-Myers Squibb, the manufactorers of dapagliflozin and saxagliptin.