Background and aims: To evaluate the efficacy, tolerability, and safety of once-weekly albiglutide (Albi) compared to placebo (Pbo), sitagliptin (Sita), or glimepiride (Glim) in patients with type 2 diabetes mellitus who had inadequately controlled haemoglobin A1c (HbA1c: 7−10%) on metformin (Met).
Materials and methods: The 3-year trial was designed as a randomised, double-blind, Pbo- and active-controlled, Phase III study. Subjects taking stable Met were randomised to Albi (30 mg), Pbo, Sita (100 mg), or Glim (2 mg). Patients meeting predefined hyperglycaemia criteria qualified for blinded dose titration (Glim 2 to 4 mg; Albi 30 to 50 mg). Patients were allowed to continue in the study if rescue for persistent hyperglycaemic rescue was required. The primary objective was to evaluate HbA1c change from baseline at Week 104, using an analysis of covariance model adjusting for baseline HbA1c, region, prior myocardial infarction history, and age.
Results: Baseline age was 54.5 years (mean, SD 10.0), BMI 32.6 kg/m2 (5.5), weight 90.7 kg (19.3), HbA1c 8.1% (0.8), duration of diabetes 6.0 years (4.8). A reduction in HbA1c was seen in all active treatment groups. For the change in HbA1c, Albi was statistically superior compared to Pbo (−0.91%; 95% CI: −1.16, −0.65, p <0.0001), Sita (−0.35%; 95% CI: −0.53, −0.17, p = 0.0001), and Glim (−0.27%; 95% CI: −0.45, −0.09, p = 0.0033). Albi had superior reduction in fasting plasma glucose (FPG) (mmol/l) compared to Pbo (−1.53; 95% CI: −2.16, −0.90 p <0.0001), Sita (−0.86; 95% CI −1.30, −0.41, p = 0.0002) and Glim (−0.56; 95% CI −1.01, −0.12, p = 0.0133). All treatment groups (except for Glim) had modest mean weight loss at 104 weeks (Pbo: −1.00 kg, Sita: −0.86 kg, Glim: 1.17 kg, Albi: −1.21 kg). Weight change (kg) compared to Albi was similar for Pbo (−0.2; 95% CI −1.14, 0.73, p = 0.7) and Sita (−0.4; 95% CI −1.01, 0.31, p = 0.3). Albi weight loss was superior to Glim (−2.4 kg; 95% CI −3.03, −1.71, p <0.0001). Gastrointestinal adverse events through Week 104 with Pbo/Sita/Glim/Albi were nausea, 11%/7%/6%/10%; diarrhoea, 11%/9%/9%/13%; and vomiting, 1%/4%/4%/6%. Injection site reactions occurred in 5% of patients randomised to Pbo, 6% for Sita, 8% for Glim, and 17% for Albi. The incidence of pre-rescue documented (≤3.9 mmol/l) symptomatic hypoglycaemia events was 4% for Pbo, 2% for Sita, 18% for Glim, and 3% for Albi; no severe hypoglycaemia events were reported.
Conclusion: Albiglutide treatment for type 2 diabetes mellitus as add on to Met therapy was durable and superior to Sita and Glim in HbA1c and FPG reduction, superior in weight loss to Glim, and well tolerated up to Week 104
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