Sitagliptin was non-inferior to metformin in improving HbA1c in treatment-naive patients with Type 2 diabetes….
The purpose of the study was to compare the efficacy and safety of monotherapy with sitagliptin and metformin in treatment-naïve patients with Type 2 diabetes.
In a double-blind study, 1,050 treatment-naive patients (i.e. not taking an antihyperglycaemic agent for ≥16 weeks prior to study entry) with Type 2 diabetes and an HbA1c 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 ≥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 HbA1c 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%.
From a mean baseline HbA1c of 7.2% in the PP population, HbA1c 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 HbA1c influenced treatment response, with larger reductions in HbA1c observed in patients with baseline HbA1c≥8% in the sitagliptin (–1.13%; n = 74) and metformin (–1.24%; n = 73) groups. The proportions of patients at week 24 with HbA1c 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-β cell function (HOMA-β) and insulin resistance (HOMA-IR). The incidence of hypoglycemia 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 diarrhea (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).
In this 24-week monotherapy study, the results showed that sitagliptin was non-inferior to metformin in improving HbA1c in treatment-naive patients with Type 2 diabetes. Although both treatments were generally well tolerated, a lower incidence of gastrointestinal-related adverse experiences was observed with sitagliptin.