| Objective:To systematically evaluate the safety and effectiveness of once-weekly Glucagon-like Peptide-1 Receptor Agonist(GLP-1RA)compared with daily GLP-1RA for type 2 diabetes mellitus(T2DM).Methods:We searched databases including Medline,PubMed,EMbase,The Cochrane Library,CNKI and WanFang Date to select randomized controlled trials(RCTs)about once-weekly GLP-1RA versus daily GLP-1RA for T2 DM up to October 2019.According to the inclusion and exclusion criteria,two reviewers independently screened literature,extracted data and assessed methodological quality.Meta-analysis was performed using RevMan 5.3 software.Result:Our analysis include 9 RCTs involving 5988 patients.In the aspects of efficacy:(1)The results of meta-analysis showed that once-weekly GLP-1RA were more effective in reducing levels of glycated hemoglobin A1c(HbA1c)compared with daily GLP-1RA(WMD=-0.21,95%CI-0.36 to-0.05,P=0.008).The results of subgroup meta-analysis showed that once-weekly GLP-1RA was as effective as liraglutide(WMD=-0.07,95%CI-0.09 to 0.23,P=0.41)and more effective(WMD=-0.36,95%CI-0.48 to-0.24,P<0.0001)than exenatide in controlling HbA1 c.(2)Once-weekly GLP-1RA were more effective in controlling fasting blood glucose(FBG)than daily GLP-1RA,and the difference was statistically significant(WMD =-0.46,95%CI-0.81 to-0.11,P= 0.01).The results of subgroup meta-analysis showed that once-weekly GLP-1RA was as efficient as liraglutide(WMD=0.27,95%CI-0.02 to 0.55,P=0.07)and more effective(WMD=-0.75,95%CI-0.97 to-0.54,P<0.00001)than exenatide in reducing levels of FBG.(3)No significant difference was shown in the achievement rates of HbA1c(< 7%)between control group and once-weekly GLP-1RA group(OR=1.45,95%CI 0.99 to 2.21,P=0.05).The results of subgroup meta-analysis showed that once-weekly GLP-1RA group had significantly higher achievement rates of HbA1 c than exenatide group(OR=2.21,95%CI 1.63 to 3.00),P<0.00001),and similar to liraglutide group(OR=0.83,95%CI 0.67 to 1.04,P=0.10).(4)The results of meta-analysis showed statistically significant difference between once-weekly GLP-1RA and daily GLP-1RA in losing weight(WMD= 0.58,95%CI 0.15 to 1.01,P=0.009).Once-weekly GLP-1RA was as effective as exenatide(WMD=0.27,95%CI-0.3 to 0.84,P=0.36)and less effective(WMD=1.06,95%CI 0.56 to 1.57,P<0.0001)than liraglutide in controlling body weight.In the aspects of safety:(1)Once-weekly GLP-1RA had significantly lower incidence of nausea(OR=0.62,95%CI 0.43 to 0.91,P=0.01).There were no significant differences between once-weekly GLP-1RA group and daily GLP-1RA group for incidences of vomiting(OR=0.82,95%CI 0.52 to 1.28,P=0.37),diarrhea(OR= 1.20,95%CI 0.87 to 1.66,P=0.27)and hypoglycemia(OR=0.89,95%CI 0.62 to 1.28,P=0.52).(2)Liraglutide group had higher incidences of nausea(OR=0.50,95%CI 0.27,0.90,P=0.02),vomiting(OR=0.50,95% CI 0.30 to 0.86,P=0.01)and lower incidences of hypoglycemia(OR=1.57,95%CI 1.19 to 2.06,P=0.001)than once-weekly GLP-1RA.Incidences of diarrhea showed no significant difference between the two groups(OR=0.95,95%CI 0.52 to 1.76,P=0.88).(3)Exenatide group had lower incidences of diarrhea(OR=1.42,95%CI 1.07 to 1.89,P=0.02),and higher incidences of hypoglycemia(OR=0.61,95%CI 0.47 to 0.78,P=0.0001)than once-weekly GLP-1RA group.Incidences of nausea(OR=0.71,95% CI 0.44 to 1.14,P=0.15)and vomiting(OR=1.02,95%CI 0.59 to 1.78,P=0.94)showed no significant difference between the two groups.Conclusion:1.Once-weekly GLP-1RAs are superior to daily GLP-1RAs in controlling T2 DM patients,levels of HbA1 c and FBG without more gastrointestinal adverse reaction and incidences of hypoglycemia,but daily GLP-1RAs are more effective in decreasing body weight than daily GLP-1RAs.2.Once-weekly GLP-1RAs was as effective as liraglutide in reduceing T2 DM patients,levels of HbA1 c and FBG,achievement rates of HbA1 c,but has higher incidence of gastrointestinal adverse events..Liraglutide is superior to once-weekly GLP-1RAs in losing weight.3.Once-weekly GLP-1RAs are more effective in controlling HbA1 c and FBG and higher achievement rates of HbA1 c than exenatide,with lower incidences of hypoglycemia. |
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