Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are indicated for restoring normoglycemia in patients with type 2 diabetes (T2D). This review analyzed and compared the efficacy results from 30 trials with the once-weekly (OW) GLP-1 RAs albiglutide, dulaglutide, exenatide extended-release (ER) and semaglutide. The 4 OW GLP-1 RAs showed a higher reduction in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG) and body weight, when compared to placebo. Semaglutide significantly reduced the HbA1c level (estimated treatment difference [ETD]: -0.62%; 95% confidence interval [CI], -0.79 to -0.44; P<0.0001), FPG (ETD: -15 mmol/L; 95% CI, -22 to -8.3; P<0.0001) and body weight (ETD: -3.73 kg; 95% CI, -4.53 to -2.93; P<0.0001) compared with exenatide ER. A direct comparison between OW, once-daily (OD), and twice-daily (BD) GLP-1 RAs indicated some trends in efficacy, for example, with OD liraglutide, providing a significant reduction in body weight vs albiglutide (ETD: 1.55 kg; 95% CI, 1.05-2.06; P<0.0001 for albiglutide), dulaglutide (ETD: 0.71 kg; 95% CI, 0.17 -1.26; P=0.011 for dulaglutide), and exenatide ER (ETD: 0.90 kg; 95% CI, 0.39- 1.40; P=0.0005 for exenatide ER). OW GLP-1 RAs also offered improved glycemic control when compared with the dipeptidyl peptidase-4 inhibitor sitagliptin. In conclusion, OW GLP-1 RAs offer a valid therapeutic option for T2D.