The effect of initial therapy with the fixed-dose combination of sitagliptin and metformin compared with metformin monotherapy in patients with type 2 diabetes mellitus

Aims: This study was conducted to compare the glycaemic efficacy and safety of initial combination therapy with the fixed‐dose combination of sitagliptin and metformin versus metformin monotherapy in drug‐naive patients with type 2 diabetes. Methods: This double‐blind study (18‐week Phase A and 26‐week Phase B) randomized 1250 drug‐naÏve patients with type 2 diabetes mean baseline haemoglobin A1c (HbA1c) 9.9%] to sitagliptin/metformin 50/500 mg bid or metformin 500 mg bid (uptitrated over 4 weeks to achieve maximum doses of sitagliptin/metformin 50/1000 mg bid or metformin 1000 bid). Results of the primary efficacy endpoint (mean HbA1c reductions from baseline at the end of Phase A) are reported herein. Results: At week 18, mean change from baseline HbA1c was ?2.4% for sitagliptin/metformin FDC and ?1.8% for metformin monotherapy (p < 0.001); more patients treated with sitagliptin/metformin FDC had an HbA1c value <7% (p < 0.001) versus metformin monotherapy. Changes in fasting plasma glucose were significantly greater with sitagliptin/metformin FDC (?3.8 mmol/l) versus metformin monotherapy (?3.0 mmol/l; p < 0.001). Homeostasis model assessment of β‐cell function (HOMA‐β) and fasting proinsulin/insulin ratio were significantly improved with sitagliptin/metformin FDC versus metformin monotherapy. Baseline body weight was reduced by 1.6 kg in each group. Both treatments were generally well tolerated with a low and similar incidence of hypoglycaemia. Abdominal pain (1.1 and 3.9%; p = 0.002) and diarrhoea (12.0 and 16.6%; p = 0.021) occurred significantly less with sitagliptin/metformin FDC versus metformin monotherapy; the incidence of nausea and vomiting was similar in both groups. Conclusion: Compared with metformin monotherapy, initial treatment with sitagliptin/metformin FDC provided superior glycaemic improvement with a similar degree of weight loss and lower incidences of abdominal pain and diarrhoea.