BACKGROUND: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) are 
new drugs for the treatment of type 2 diabetes.
PURPOSE: To summarize evidence for the cardiometabolic efficacy and adverse 
effects of once-weekly GLP-1RAs in adults with type 2 diabetes.
DATA SOURCES: Electronic databases (PubMed, Web of Science, Cochrane Central 
Register of Controlled Trials, U.S. Food and Drug Administration, European 
Medicines Agency, ClinicalTrials.gov) and congress abstracts from inception 
through 26 September 2015.
STUDY SELECTION: Randomized, controlled trials (≥ 24 weeks of follow-up) 
studying albiglutide, dulaglutide, once-weekly exenatide, semaglutide, and 
taspoglutide and reporting a cardiometabolic (primary outcome, hemoglobin A1c 
[HbA1c]) or safety outcome.
DATA EXTRACTION: Extraction was done in duplicate, and risk of bias was 
assessed. No language restriction was applied.
DATA SYNTHESIS: 34 trials (21,126 participants) were included. Compared with 
placebo, all once-weekly GLP-1RAs reduced HbA1c and fasting plasma glucose; 
taspoglutide, 20 mg, once-weekly exenatide, and dulaglutide, 1.5 mg, reduced 
body weight. Among once-weekly GLP-1RAs, the greatest differences were found 
between dulaglutide, 1.5 mg, and taspoglutide, 10 mg, for HbA1c (-0.4% [95% CI, 
-0.7% to -0.2%]), once-weekly exenatide and albiglutide for fasting plasma 
glucose (-0.7 mmol/L [CI, -1.1 to -0.2 mmol/L]; -12.6 mg/dL [CI, -19.8 to -3.6 
mg/dL]), and taspoglutide, 20 mg, and dulaglutide, 0.75 mg, for body weight 
(-1.5 kg [CI, -2.2 to -0.8]). Clinically marginal or no differences were found 
for blood pressure, blood lipid levels, and C-reactive protein levels. 
Once-weekly exenatide increased heart rate compared with albiglutide and 
dulaglutide (1.4 to 3.2 beats/min). Among once-weekly GLP-1RAs, the risk for 
hypoglycemia was similar, whereas taspoglutide, 20 mg, had the greatest risk for 
nausea (odds ratios, 1.9 to 5.9).
LIMITATION: Data were unavailable for semaglutide, definitions of outcomes were 
heterogeneous, the last-observation-carried-forward imputation method was used 
in 73% of trials, and publication bias is possible.
CONCLUSION: Compared with other once-weekly GLP-1RAs, dulaglutide, 1.5 mg; 
once-weekly exenatide; and taspoglutide, 20 mg, showed a greater reduction of 
HbA1c, fasting plasma glucose, and body weight. Taspoglutide, 20 mg, had the 
highest risk for nausea; risk for hypoglycemia among once-weekly GLP-1RAs was 
similar.
PRIMARY FUNDING SOURCE: Sanofi Aventis (grant to the University of Leicester).