AIM: To compare the efficacy and safety of monotherapy with sitagliptin and metformin in treatment-naïve patients with type 2 diabetes. METHODS: In a double-blind study, 1050 treatment-naïve patients (i.e. not taking an antihyperglycaemic agent for > or =16 weeks prior to study entry) with type 2 diabetes and an HbA(1c) 6.5-9% were randomized (1:1) to treatment with once-daily sitagliptin 100 mg (N = 528) or twice-daily metformin 1000 mg (N = 522) for 24 weeks. Metformin was up-titrated from 500 to 2000 mg per day (or maximum tolerated daily dose > or =1000 mg) over a period of 5 weeks. The primary analysis used a per-protocol (PP) approach to assess whether sitagliptin was non-inferior to metformin based on HbA(1c) change from baseline at week 24. Non-inferiority was to be declared if the upper boundary of the 95% confidence interval (CI) for the between-group difference in this endpoint was <0.40%. RESULTS: From a mean baseline HbA(1c) of 7.2% in the PP population, HbA(1c) change from baseline was -0.43% with sitagliptin (n = 455) and -0.57% with metformin (n = 439). The between-group difference (95% CI) was 0.14% (0.06, 0.21), thus confirming non-inferiority. Baseline HbA(1c) influenced treatment response, with larger reductions in HbA(1c) observed in patients with baseline HbA(1c)> or =8% in the sitagliptin (-1.13%; n = 74) and metformin (-1.24%; n = 73) groups. The proportions of patients at week 24 with HbA(1c) values at the goals of <7 or <6.5% were 69 and 34% with sitagliptin and 76 and 39% with metformin, respectively. Fasting plasma glucose changes from baseline were -11.5 mg/dL (-0.6 mmol/l) and -19.4 mg/dl (-1.1 mmol/l) with sitagliptin and metformin, respectively (difference in LS mean change from baseline [95% CI] = 8.0 mg /dl [4.5,11.4]). Both treatments led to similar improvements from baseline in measures of homeostasis model assessment-beta cell function (HOMA-beta) and insulin resistance (HOMA-IR). The incidence of hypoglycaemia was 1.7% with sitagliptin and 3.3% with metformin (p = 0.116). The incidence of gastrointestinal-related adverse experiences was substantially lower with sitagliptin (11.6%) compared with metformin (20.7%) (difference in incidence [95% CI] = -9.1% [-13.6,-4.7]), primarily because of significantly decreased incidences of diarrhoea (3.6 vs. 10.9%; p < 0.001) and nausea (1.1 vs. 3.1%; p = 0.032). Body weight was reduced from baseline with both sitagliptin (LS mean change [95% CI] = -0.6 kg [-0.9,-0.4]) and metformin (-1.9 kg [-2.2, -1.7]) (p < 0.001 for sitagliptin vs. metformin). CONCLUSIONS: In this 24-week monotherapy study, sitagliptin was non-inferior to metformin in improving HbA(1c) in treatment-naïve patients with type 2 diabetes. Although both treatments were generally well tolerated, a lower incidence of gastrointestinal-related adverse experiences was observed with sitagliptin.
RCT Entities:
AIM: To compare the efficacy and safety of monotherapy with sitagliptin and metformin in treatment-naïve patients with type 2 diabetes. METHODS: In a double-blind study, 1050 treatment-naïve patients (i.e. not taking an antihyperglycaemic agent for > or =16 weeks prior to study entry) with type 2 diabetes and an HbA(1c) 6.5-9% were randomized (1:1) to treatment with once-daily sitagliptin 100 mg (N = 528) or twice-daily metformin 1000 mg (N = 522) for 24 weeks. Metformin was up-titrated from 500 to 2000 mg per day (or maximum tolerated daily dose > or =1000 mg) over a period of 5 weeks. The primary analysis used a per-protocol (PP) approach to assess whether sitagliptin was non-inferior to metformin based on HbA(1c) change from baseline at week 24. Non-inferiority was to be declared if the upper boundary of the 95% confidence interval (CI) for the between-group difference in this endpoint was <0.40%. RESULTS: From a mean baseline HbA(1c) of 7.2% in the PP population, HbA(1c) change from baseline was -0.43% with sitagliptin (n = 455) and -0.57% with metformin (n = 439). The between-group difference (95% CI) was 0.14% (0.06, 0.21), thus confirming non-inferiority. Baseline HbA(1c) influenced treatment response, with larger reductions in HbA(1c) observed in patients with baseline HbA(1c)> or =8% in the sitagliptin (-1.13%; n = 74) and metformin (-1.24%; n = 73) groups. The proportions of patients at week 24 with HbA(1c) values at the goals of <7 or <6.5% were 69 and 34% with sitagliptin and 76 and 39% with metformin, respectively. Fasting plasma glucose changes from baseline were -11.5 mg/dL (-0.6 mmol/l) and -19.4 mg/dl (-1.1 mmol/l) with sitagliptin and metformin, respectively (difference in LS mean change from baseline [95% CI] = 8.0 mg /dl [4.5,11.4]). Both treatments led to similar improvements from baseline in measures of homeostasis model assessment-beta cell function (HOMA-beta) and insulin resistance (HOMA-IR). The incidence of hypoglycaemia was 1.7% with sitagliptin and 3.3% with metformin (p = 0.116). The incidence of gastrointestinal-related adverse experiences was substantially lower with sitagliptin (11.6%) compared with metformin (20.7%) (difference in incidence [95% CI] = -9.1% [-13.6,-4.7]), primarily because of significantly decreased incidences of diarrhoea (3.6 vs. 10.9%; p < 0.001) and nausea (1.1 vs. 3.1%; p = 0.032). Body weight was reduced from baseline with both sitagliptin (LS mean change [95% CI] = -0.6 kg [-0.9,-0.4]) and metformin (-1.9 kg [-2.2, -1.7]) (p < 0.001 for sitagliptin vs. metformin). CONCLUSIONS: In this 24-week monotherapy study, sitagliptin was non-inferior to metformin in improving HbA(1c) in treatment-naïve patients with type 2 diabetes. Although both treatments were generally well tolerated, a lower incidence of gastrointestinal-related adverse experiences was observed with sitagliptin.