Dapagliflozin combined with metformin is a safe and effective long-term type 2 diabetes treatment

This study compared the long-term (4-year) safety and efficacy of two glucose-lowering medications, dapagliflozin (Farxiga) and glipizide (Glucotrol), when used in combination with metformin (Glucophage) in patients with type 2 diabetes.

Type 2 diabetes is a progressive disease. While blood glucose (sugar) levels may initially be controlled with metformin, other medications will eventually need to be added. Sulfonylureas (such as glipizide) and insulin are often added to metformin, but these treatments have been associated with weight gain and an increased risk of hypoglycemia (dangerously low blood glucose). For these reasons, patients often do not take these medications as they should.

Dapagliflozin is a therapy that decreases the amount of glucose reabsorbed by the kidneys into the bloodstream. The glucose is excreted through urine instead. This treatment has been shown to be safe and effective over 104 weeks when combined with metformin. Dapagliflozin decreased HbA1c levels (average blood glucose over 3 months), body weight, and hypoglycemic episodes compared to glipizide. However, a truly effective type 2 diabetes treatment must be effective in the long-term.

The current study examined the safety and efficacy of dapagliflozin over 4 years, compared to that of glipizide. The study included 392 patients randomly assigned to receive dapagliflozin plus metformin (Group 1) or glipizide plus metformin (Group 2).  HbA1c levels, fasting blood glucose levels (glucose levels after a period without food or drink), body weight, and adverse events were assessed at the start of the study (baseline) and at 52, 104, and 208 weeks.

Average HbA1c levels decreased in both groups from baseline to week 52 (0.50% decrease in Group 1; 0.48% decrease in Group 2). There was a gradual increase in HbA1c levels from week 104 to week 208 in both groups. HbA1c levels increased more in Group 2 (0.20% higher than baseline) compared to Group 1 (0.10% lower than baseline).

Average fasting blood glucose levels were lower in Group 1 (0.7 mmol/L lower than baseline) compared to Group 2 (0.2 mmol/L lower than baseline). After 52 weeks patients in Group 1 had lost an average 3.89 kg, by 208 weeks they had lost an average of 3.65 kg. Patients in Group 2 gained an average of 0.73 kg after 208 weeks.

Adverse events were experienced by 87.7% of patients in Group 1 and 87.0% of Group 2. Common adverse events included colds (17.2% of Group 1, 18.6% of Group 2), influenza (12.3% of Group 1, 11% of Group 2), and hypertension (high blood pressure; 10.8% of Group 1, 15.2% of Group 2). Urinary tract infections occurred more often in Group 1 (11.8%) than in Group 2 (7.8%).

This study concluded that dapagliflozin led to greater reductions in HbA1c and body weight compared to glipizide, and is a safe and effective long-term treatment for type 2 diabetes.

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