Glucagon-Like Peptide-1 (GLP-1) Analogue Versus Insulin In Inadequately Controlled Patients With Type 2 Diabetes Mellitus: A Meta-analysis Of Clinical Trials

Background The introduction of GLP-1 analogue has led to a novel choice in T2DM treatment, but their role in the management of T2DM is not well defined, especially compared to insulin.Objective The aim of this study was to compare the effect and safety of GLP-1 analogue with insulin therapy on type 2 diabetes mellitus patients inadequately controlled with metformin (and/or sulfonylurea).Research design and methods A systematic literature search on Medline, Embase and Cochrane for randomized controlled trials was conducted using specific search terms"GLP-1 analogue insulin type2 diabetes clinical trials"and 8 eligible studies were retrieved. Data on mean change in HbA1C, weight loss, FPG, incidence of hypoglycemia and gastrointestinal adverse events were extracted from each study and pooled in meta-analysis. Data on PPG and serious adverse events were also extracted and described or tabulated.Result Data from eight RCTs enrolling 2782 patients were pooled using a random-effects model. The mean net change(95% confidence interval) for HbA1c, weight loss and FPG for patients treated with GLP-1 analogue as compared with insulin was -0.14%(95%CI [-0.27 to -0.02 %]; P=0.03); -4.40kg (95%CI[-5.23 to -3.56]; P<0.05);1.18mmol/l (95%CI [0.43 to 1.93mmol/l]; P<0.05), respectively, with negative values favoring GLP-1 and positive values favoring insulin. The GLP-1 group described a greater reduction in PPG than did insulin group. Overall hypoglycemia was less reported in GLP-1 group (MH-OR 0.45, 95%CI [0.27,0.76]; P<0.01) while there is no significant difference in occurrence of severe hypoglycemia(MH-OR 0.65, 95%CI[0.29,1.45]; P=0.29). A significant higher number of gastrointestinal adverse events were reported with GLP-1 group(MH-OR 15.00; 95%CI[5.44,41.35] P<0.01).Conclusions In summary, GLP-1 analogue is a promising new agent compared with insulin. However, it can not be considered as a substitution of insulin. Further prospective clinical trials are expected to fully evaluate the long-term effectiveness and safety of these therapies within the T2DM treatment paradigm.