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Sitagliptin noninferior to metformin for A1C reduction in treatment-naive subjects with type 2 diabetes, study results show

Wednesday, March 10 2010 | Comments

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What's This? Among treatment-naive patients with type 2 diabetes, sitagliptin phosphate, an oral dipeptidyl peptidase-IV inhibitor, appears to be noninferior to metformin for improving hemoglobin A1C levels and to have a better gastrointestinal (GI) safety profile, according to new findings.

The double-blind trial included 1,050 individuals with type 2 diabetes who had not received any antihyperglycemic agent for >=16 weeks before entry into the study. After a 2-week run-in period, the subjects were randomized to receive sitagliptin 100 mg once a day or metformin 1,000 mg twice a day (down-titration to 1,000 mg once a day was permitted if intolerance occurred) for 24 weeks. All of the participants were instructed to follow a prescribed diet and exercise regimen.

The per-protocol population had a mean baseline A1C level of 7.2%.

An assessment of A1C levels at 24 weeks, the study's primary endpoint, revealed that the least-squares mean change from baseline was a reduction of 0.43 percentage point in the sitagliptin group and 0.57 percentage point in the metformin group. The between-group difference for this endpoint was 0.14 percentage point, which the researchers noted was less than the prespecified noninferiority margin of 0.4 percentage point and thereby demonstrated sitagliptin's noninferiority relative to metformin for A1C reduction.

Both treatments achieved maximal A1C efficacy by 18 weeks. In addition, A1C reductions were more pronounced in patients in both groups who had a baseline A1C that was >=8%, with average reductions of 1.13 percentage points among those who were treated with sitagliptin and 1.24 percentage points among those treated with metformin.

However, at 24 weeks, a larger proportion of the subjects in the metformin group (76%) than of those in the sitagliptin group (69%) achieved an A1C level <7%. In addition, treatment with metformin led to a statistically significantly greater reduction in weight from baseline (reduction of 1.9 kg with metformin vs 0.9 kg with sitagliptin).

Both treatments were generally well-tolerated, although the incidence of drug-related adverse events was lower with sitagliptin (5.9%) as compared with metformin (16.7%). The researchers attributed this finding primarily to the incidence of GI-related adverse events, with 10.9% of the metformin-treated patients experiencing diarrhea compared with 3.6% in the sitagliptin group, and a respective 3.1%  and 1.1% experiencing nausea. Both of these differences were statistically significant.

"The results of this study provide additional data on the use of sitagliptin as initial monotherapy for patients with type 2 diabetes mellitus," the authors noted. (Aschner P, et al. Diabetes Obes Metab 2010;12:252-261.)

This study was funded by Merck & Co. Inc.

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