ROME — A 1.7% reduction in hemoglobin A1c was achieved in patients with type 2 diabetes given the combination of sitagliptin plus metformin in a 1-year extension of a 54-week phase III trial.
This reduction, seen after 104 weeks of total follow-up, was significantly better than the reductions achieved with either drug alone or placebo, and was associated with no more adverse events than metformin monotherapy.
Dr. Debora Williams-Herman of Merck Research Laboratories in Rahway, N.J., presented the data at the annual meeting of the European Association for the Study of Diabetes.
The extension trial involved 454 patients who had already completed 1 year of treatment with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin alone at a dose of 100 mg/day; twice-daily treatment with metformin alone at a dose of 500 mg or 1,000 mg; both drugs in combination (50 mg sitagliptin plus either 500 or 1,000 mg of metformin); or placebo and 100 mg metformin. The results of this investigation were published last year and showed that, at 54 weeks' follow-up, the mean change from baseline in hemoglobin A1c (HbA1c) level was −1.8% in patients given the 50-mg sitagliptin/1,000 mg metformin combination (Diabetes Care 2007;30:1979-87).
Now, at 2 years, the results show a similar and sustained reduction in HbA1c,, compared with the original baseline values, with a −1.7% mean change in HbA1c in the 105 patients who were treated with the sitagliptin and higher-dose metformin combination. A mean change of −1.4% in HbA1c was reported in the 96 patients who were given the sitagliptin plus lower-dose metformin combination, with mean changes in HbA1c of −1.3%, −1.1%, and −1.1% in the metformin 1,000 mg/day, metformin 500 mg/day, and sitagliptin 100 mg/day groups, respectively.
Almost two-thirds (60%) of patients given the sitagliptin plus higher-dose metformin combination achieved an HbA1c below 7%, compared with 45% each for patients given the sitagliptin plus lower-dose metformin combination and those given 1,000 mg metformin. Approximately one-third (32%) of patients given sitagliptin monotherapy and 28% of those treated with metformin 500 mg achieved an HbA1c of less than 7%.
As expected, patients who had a higher initial baseline HbA1c achieved greater overall reductions in blood glucose over the course of the 2-year follow-up.
Dr. Williams-Herman reported that 5 of 107 patients (5%) given the sitagliptin plus higher-dose metformin combination experienced hypoglycemia during the extension study (i.e., between weeks 54 and 104). This can be compared with 2 of 100 patients (2%) given sitagliptin plus metformin 500 mg, 2 of 88 patients (2%) given metformin 1,000 mg, 1 of 85 patients (2%) given metformin 500 mg, and 1 of 42 patients (2%) given placebo and then 1,000 mg metformin. No patients given sitagliptin monotherapy developed hypoglycemia during the extension study.
“In patients with type 2 diabetes inadequately treated with diet and exercise, initial combination therapy with sitagliptin and metformin over 2 years showed substantial glycemic improvement,” she said.
Commenting on these data at a press briefing organized by Merck Sharp & Dohme, which markets sitagliptin, Dr. Bernard Charbonnel of the University Hospital of Nantes, France, said sitagliptin and metformin used together produced “powerful glycemic improvements.” He added: “Around 60% of patients achieved the HbA1c goal of less than 7% at 2 years, which is rather impressive.”