- In patients with type 2 diabetes mellitus (T2DM), triple therapy with dapagliflozin, saxagliptin, and metformin was associated with greater reductions in HbA1c, body weight, systolic BP, incidence of hypoglycaemia compared with glimepiride and metformin.
Why this matters
- Sulphonylureas, widely used second-line treatment for T2DM, are associated with hypoglycaemia and weight gain.
- In this double-blind, active-controlled phase 4 study, 939 patients with T2DM receiving metformin were randomly assigned 1:1:1 to receive add-on dapagliflozin, dapagliflozin plus saxagliptin or glimepiride.
- Funding: AstraZeneca.
- At 52 weeks, adjusted mean change in HbA1c was −0.82% for add-on dapagliflozin, −1.20% for add-on dapagliflozin plus saxagliptin vs −0.99% for add-on glimepiride.
- Both dapagliflozin groups were noninferior to glimepiride (predefined noninferiority margin in mean HbA1c change, 0.3%).
- Dapagliflozin plus saxagliptin was superior to glimepiride (P=.001).
- Dapagliflozin plus saxagliptin and dapagliflozin vs glimepiride were associated with significantly greater:
- changes in body weight (−3.2 kg and −3.5 kg vs +1.8 kg) and
- systolic BP (−6.4 mmHg and −5.6 mmHg vs −1.6 mmHg).
- Total 10, 19 and 329 hypoglycaemic events were reported with add-on dapagliflozin, dapagliflozin plus saxagliptin and glimepiride, respectively.
- Adverse event-related discontinuation rates were 8.6%, 3.8% and 4.2% with add-on dapagliflozin, dapagliflozin plus saxagliptin and glimepiride, respectively.
- Long-term effects on renal function were not monitored.