Pratley RE, et al. - A comparative analysis was performed of the semaglutide treatment with dulaglutide therapy in patients with inadequately controlled type 2 diabetes. Data demonstrated the superiority of semaglutide at low and high doses over dulaglutide in improving glycaemic control and reducing bodyweight. This, in turn, led to the achievement of clinically significant glycaemic targets and weight loss, with a similar safety profile in a significantly greater number of patients with type 2 diabetes.

Methods

• The setting of this open-label, parallel-group, phase 3b trial was at 194 hospitals, clinical institutions or private practices in 16 countries.
• Participants were aged 18 years or older and had type 2 diabetes with HbA1c 7.0-10.5% (53.0-91.0 mmol/mol) on metformin monotherapy.
• They were randomly allocated (1:1:1:1) via an interactive web-response system to once a week treatment with either semaglutide 0.5 mg, dulaglutide 0.75 mg, semaglutide 1.0 mg, or dulaglutide 1.5 mg subcutaneously.
• The primary endpoint included change from baseline in percentage HbA1c.
• Secondary endpoint consisted of change in bodyweight, both at week 40.
• Herein, the primary analysis population encompassed all randomly assigned patients exposed to at least one dose of trial product obtained while on treatment and before the onset of rescue medication.
• Safety cohort involved all randomly assigned patients exposed to at least one dose of trial product obtained while on treatment.
• This study was powered for HbA1c non-inferiority (margin 0.4%) and bodyweight superiority.

Results

• A total of 1,201 patients were randomly allocated to treatment between Jan 6, 2016, and June 22, 2016, out of which 301 were exposed to semaglutide 0.5 mg, 299 to dulaglutide 0.75 mg, 300 to semaglutide 1.0 mg, and 299 to dulaglutide 1.5 mg.
• It was noted that 72 (6%) patients withdrew from the trial (22 receiving semaglutide 0.5 mg, 13 receiving dulaglutide 0.75 mg, 21 receiving semaglutide 1.0 mg, and 16 receiving dulaglutide 1.5 mg).
• A reduction was achieved in the mean percentage HbA1c by 1.5 (SE 0.06) percentage points with semaglutide 0.5 mg vs 1.1 (0.05) percentage points with dulaglutide 0.75 mg (estimated treatment difference [ETD] -0.40 percentage points [95% CI -0.55 to -0.25]; p < 0.0001) and by 1.8 (0.06) percentage points with semaglutide 1.0 mg vs 1.4 (0.06) percentage points with dulaglutide 1.5 mg (ETD -0.41 percentage points [-0.57 to -0.25]; p < 0.0001) from overall baseline mean.
• From overall baseline mean, it was discovered that the mean bodyweight was reduced by 4.6 kg (SE 0.28) with semaglutide 0.5 mg compared with 2.3 kg (0.27) with dulaglutide 0.75 mg (ETD -2.26 kg [-3.02 to -1.51]; p < 0.0001) and by 6.5 kg (0.28) with semaglutide 1.0 mg vs 3.0 kg (0.27) with dulaglutide 1.5 mg (ETD -3.55 kg [-4.32 to -2.78]; p < 0.0001).
• The most frequently reported adverse event were gastrointestinal disorders, reported in 129 (43%) of 301 patients receiving semaglutide 0.5 mg, 133 (44%) of 300 subjects receiving semaglutide 1.0 mg, 100 (33%) of 299 candidates receiving dulaglutide 0.75 mg, and in 143 (48%) of 299 patients receiving dulaglutide 1.5 mg.
• Furthermore, gastrointestinal disorders appeared to be the most common reason for discontinuing therapy with semaglutide and dulaglutide.
• Six fatalities were disclosed: 1 in each semaglutide group and 2 in each dulaglutide group.