Debora Williams-Herman, MD, Senior Investigator at Merck Research Laboratories, Rahway, New Jersey, United States, presented results from a recent clinical trial that found that patients treated with a combination of sitagliptin and metformin achieved significant and sustained improvement in blood sugar control over a one-year period compared to metformin monotherapy, and that the combination therapy was generally well tolerated.

Following the initial 24-week placebo-controlled phase (n=1091) of the study, 748 subjects with a mean baseline HbA1c of 8.7% entered the open-label phase, continuing for another 30-weeks on their initial treatment regimens.

The groups were: sitagliptin 50 mg/metformin 1000 mg BID (n=157); sitagliptin 50 mg/metformin 500 mg BID (n=148); metformin 1000 mg BID(n=137); metformin 500 mg BID (n=122); and sitagliptin 100 mg once daily (n=106).

At 54 weeks, the investigators found a mean HbA1c reduction from baseline of 1.8% for subjects treated with combination sitagliptin 50 mg/metformin 1000 mg BID for up to 54 weeks (n=153). They also found mean HbA1c reductions from baseline of 1.4% for subjects treated with sitagliptin 50 mg/metformin 500 mg BID (n=147), 1.3% for subjects treated with metformin 1000 mg BID (n=134), 1.0% for subjects treated with metformin 500 mg BID (n=117), and 0.8% for subjects treated with sitagliptin 100 mg once daily (n=106).

In terms of achieving the target HbA1c of < 7%, 67% of the sitagliptin 50 mg/metformin 1000 mg BID subjects achieved the target A1c, compared to 44% on metformin 1000 mg BID monotherapy.

Dr. Williams-Herman reported that 48% of the subjects treated with sitagliptin 50 mg/metformin 500 mg BID, 25% of those treated with metformin 500 mg BID, and 23% of those treated with sitagliptin 100 mg once daily reached the target HbA1c goal.

Notably, HbA1c percentage reductions at Week-54 for each active treatment group did not differ significantly from percentage reductions achieved at Week-24, suggesting that the treatment effect of each therapy held for a year and that the superior efficacy of combination sitagliptin/metformin was not diminished over a longer period of use.

Adverse events were generally comparable among the treatment groups. Rates of hypoglycemia were low across all groups, and rates of gastrointestinal adverse events were similar across all groups. There was a slight mean loss of body weight (less than 2 kg) in all groups except sitagliptin 100 mg (gain of less than 1 kg).

“In summary,” said Dr. Williams-Herman, “in patients with type 2 diabetes inadequately controlled by diet and exercise, initial combination therapy with sitagliptin and metformin over one year showed consistent and substantial glycemic improvement, a small reduction in body weight, and a favorable safety profile.”