Benefits and Harms of Once-Weekly XXXX Agonist Treatments: A Systematic Review and Network Meta-analysis.

@entity1 @entity390 @entity6 @entity22259 @entity4053 @entity8142 @entity413 @entity48142
BACKGROUND: Once-weekly @entity8142 agonists (GLP-1RAs) are new drugs for the treatment of type 2 @entity6 . PURPOSE: To summarize evidence for the cardiometabolic efficacy and adverse effects of once-weekly GLP-1RAs in adults with type 2 @entity6 . 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 @entity22259 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 @entity1 ) were included. Compared with placebo, all once-weekly GLP-1RAs reduced HbA1c and fasting plasma @entity413 ; @entity22259 , 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 @entity22259 , 10 mg, for HbA1c (-0.4% [95% CI, -0.7% to -0.2%]), once-weekly exenatide and albiglutide for fasting plasma @entity413 (-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 @entity22259 , 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 @entity48142 (1.4 to 3.2 beats/min). Among once-weekly GLP-1RAs, the risk for @entity4053 was similar, whereas @entity22259 , 20 mg, had the greatest risk for @entity390 (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 @entity22259 , 20 mg, showed a greater reduction of HbA1c, fasting plasma @entity413 , and body weight. @entity22259 , 20 mg, had the highest risk for @entity390 ; risk for @entity4053 among once-weekly GLP-1RAs was similar. PRIMARY FUNDING SOURCE: Sanofi Aventis (grant to the University of Leicester).
