San Diego, CA—Adding saxagliptin to metformin instead of increasing the dose of metformin significantly improves levels of hemoglobin (Hb)A1c, fasting plasma glucose, and postprandial glucose in patients with type 2 diabetes who demonstrate inadequate glycemic control despite receiving a stable dose of metformin, according to the results of a randomized, open-label study presentedat the 71st Scientific Sessions of the American Diabetes Association.
Early use of combination therapy may offer glycemic control and tolerability superior to that gained from uptitrating metformin to its maximal dose, because metformin doses >1500 mg daily may produce gastrointestinal distress, with only minimal incremental efficacy over doses of 500 to 1000 mg daily, said Vivian Fonseca, MD, Professor of Medicine and Pharmacology, and Chief, Section of Endocrinology, Tulane University, New Orleans.
“Metformin is a wonderful drug, but it has problems with tolerability, particularly at higher doses; this has been known for a long time,” he said. “Gastrointestinal side effects are fairly common, so people don’t often go to the maximal doses. The question is, is it better to uptitrate or is it better to add on a second drug?”
The double-blind study included 282 adults who have had type 2 diabetes for a mean duration of 6 years and an HbA1c level of 7.0% to 10.5%, despite undergoing therapy with metformin XR 1500 mg daily. They were randomized to saxagliptin 5 mg daily plus metformin XR 1500 mg daily or to metformin uptitrated to 2000 mg daily.
At 18 weeks, HbA1c had decreased 0.88% from baseline in patients who received saxagliptin plus metformin XR compared with 0.35% in those who received uptitrated metformin. Fasting plasma glucose levels declined by 20.2 mg/dL versus 6.9 mg/dL from baseline, respectively, and postprandial glucose levels fell by 31.5 mg/dL and 8.2 mg/dL.
Among patients receiving saxagliptin added to metformin XR, 51% demonstrated an HbA1c level <7% compared with 37% of those who received uptitrated metformin XR.
The proportion of patients experiencing adverse events was similar in the 2 groups. Hypoglycemic events were observed in 3.6% of patients taking saxagliptin/metformin XR and in 1.4% of those taking uptitrated metformin XR; all hypoglycemic events were mild or moderate, and none led to discontinuation of study drugs.
The results show that saxagliptin is an appropriate add-on option for patients whose HbA1c level remains above goal on metformin monotherapy, Dr Fonseca said. The earlier use of combination therapy may provide better glycemic control than uptitrating metformin to its maximum dose, he added.