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A controlled trial has found that the combination of sitagliptin plus metformin has a greater effect on glycated haemoglobin (HbA1c) than either singly.
The study authors note that metformin and sitagliptin lower blood glucose by potentially complementary mechanisms, so their use in combination may have greater activity than either alone.
The trial had five treatment arms plus a placebo arm, and involved patients with type 2 diabetes not controlled by diet and lifestyle measures and HbA1c >7.5%; current oral hypoglycaemic drug treatment was not a reason for exclusion.
Preliminary treatment included a trial of diet and lifestyle measures for those not taking oral hypoglycaemic therapy and with HbA1c >11%, a washout of any previous therapy if appropriate, and a single-blind run in period. Patients were then randomised to sitagliptin 100mg daily, metformin 1g or 2g daily, or sitagliptin 100mg daily plus either 1g or 2g metformin daily, or placebo.
Study duration was 24 weeks and the primary endpoint was change in HbA1c from baseline to 24 weeks. Analysis was based on all patients treated (ie, receiving at least one dose of study medication). Those with HbA1c >11% after a trial of diet and lifestyle measures were allocated to open-label treatment with the higher-dose combination.
A total of 1,091 patients met the eligibility criteria for the double-blind portion of the study; 775 (71%) completed the 24 weeks and 1,056 (96.8%) were included in the analysis. All active treatments produced statistically significant reductions in HbA1c from baseline to week 24 compared with placebo. Reductions for the monotherapy groups were 0.83% for sitagliptin alone, 0.99% for metformin 1g and 1.3% for metformin 2g. Reductions for the combination groups were 1.57% for the combination with metformin 1g and 2.07% for that with metformin 2g; the differences between monotherapies and the combinations were also statistically significant.
Results for secondary outcomes showed a similar spread. Adverse effects were similar across the groups, and there was a low incidence of hypoglycaemia (and no instance of severe hypoglycaemia).
The authors conclude that metformin and sitagliptin have additive effects on diabetic control as measured HbA1c, with no decrease in tolerance.
Diabetes Care 2007;7 May