Sitagliptin plus metformin better than either alone?
A controlled trial found that the combination of sitagliptin plus metformin had a greater effect on glycated haemoglobin (HbA1c) than either singly. The authors of the study note that metformin and sitagliptin lower blood glucose by potentially complementary mechanisms, and that use in combination may therefore 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 1gm or 2gm daily, or sitagliptin 100mg daily plus either 1gm or 2gm 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 (i.e. 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 to placebo. Reductions for the monotherapy groups were 0.83% for sitagliptin alone, 0.99% for metformin 1gm and 1.3% for metformin 2gm. Reductions for the combination groups were 1.57% for the combination with metformin 1gm and 2.07% for that with metformin 2gm: 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, published early online 7 ay 2007; DOI: 10.2337/dc07-0627 (link to abstract).