Type 2 diabetes mellitus (T2DM) is a chronic disease that, when uncontrolled, can result in significant diabetes-related complications.1 Guidelines recommend metformin as first line therapy, but additional treatment is often necessary to achieve desired goals. New treatments such as glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to have a beneficial effect on metabolic abnormalities such as obesity, hypertension, and dyslipidemia. However, the extent of the benefits as compared to other classes of drugs such as insulin, sulphonylureas, and thiazolidinediones has been questionable.2
A 26-week randomized, double-blind, double-dummy, superiority trial was conducted in patients with T2DM who had been treated with metformin. Patients were enrolled at 72 sites in the US, India, and Mexico. The enrollment criteria included age of 18 years or older, healthy aside from a diagnosis of type 2 diabetes, must have been treated with a stable metformin regimen for at least 2 months before screening, had an HbA1c of 7.1 to 11.0% and a body-mass index (BMI) of 25 to 45 kg/m2. Pregnant women were excluded. A total of 514 patients were enrolled; however, 23 patients withdrew prior to the first dose of study drug. 160 patients were randomly assigned to receive 2 mg injected exenatide once weekly plus oral placebo once daily, 166 patients were randomly assigned to receive 100 mg oral sitagliptin once daily plus injected placebo once weekly, and 165 patients were randomly assigned to receive 45 mg oral pioglitazone once daily plus injected placebo once weekly. Randomization was computer-generated and assigned in a 1:1:1 ratio. Stratification was done based on country and by HbA1c at screening (<9.0% vs >9.0%). The intention-to-treat principle was applied to data for all enrolled patients who received at least one dose of study drug. The primary end point was change in HbA1c from baseline to week 26. A change of weight from baseline was included as a secondary endpoint.2
HbA1c after 26 weeks of treatment was more significantly reduced in the exenatide treatment group (least square mean -1.5%, 95% CI -1.7 to -1.4) compared to sitagliptin and pioglitazone treatment groups (-0.9%, -1.1 to 0.7 and -1.2%, -1.4 to 1.0, respectively). Final mean HbA1c was 7.2% (SE. 0.1) for exenatide, 7.7% (0.1) for sitagliptin, and 7.4% (0.1) for pioglitazone.2
After stratification, in patients with a baseline HbA1c <9.0%, 102 patients in the exenatide group had a change in HbA1c of -1.1%, 106 patients in the sitagliptin group had a change in HbA1c of -0.5%, and 109 patients in the pioglitazone group had a change in HbA1c of -0.9%. After 26 weeks in patients with a baseline HbA1c >9.0%, 58 patients in the exenatide group had a change in HbA1c of -2.0%, 60 patients in the sitagliptin group had a change in HbA1c of -1.3%, and 56 patients in the pioglitazone group had a change in HbA1c of -1.5%. Treatment differences between exenatide and sitagliptin were statistically significant in all patients, but the ...