IDF21-0072 Safety and Efficacy of Insulin IGlarLixi versus IDegLira: A Meta-Analysis of Fifteen studies

Abstract

Background: Combination of insulin and a GLP-1 analogue in a fixed-ratio, the once-daily injection has a promising beneficial clinical base on efficacy and safety, besides GLP-1 affects weight loss and cardiovascular protection. Up to now, there is no head-to-head comparison between IDeglira and IGlarLixi. Aim: This meta-analysis intends to evaluate clinical studies regarding assess efficacy and safety between IGlarLixi versus IDegLira indirectly comparative. Method: The eligible publication was screened using inclusion criteria such as 1) the study included minimal one month follow up; 2) be compared to a control group; 3) carried by the English language; 4) published at least from 2010, and; 5) clinical study that reached phase 1 until phase 3. Any situation which altered endocrinologic status, abstracts only, case reports, letters, comments, or reviews; animal studies; duplicate studies; no surgical intervention; and no population of interest, and receipt of any investigational product within 30 days before screening was set as exclusion criteria. Studies were searched using keywords: (IGlarLixi) OR (IDegLira) AND (Diabetes Mellitus) in several databases of Cochrane Central Register of Controlled Trials (CENTRAL), Pubmed, ClinicalTrials.gov, EMBASE. All papers were reviewed using critical appraisal for clinical trials by Centre for Evidence-Based Medicine Oxford University. The risk of bias was determined by the Cochrane Handbook by Cochrane Handbook for a randomized trial. Seventy papers were initially collected using PICO in advanced search, 20 are duplicated, and 35 articles did not fulfil the criteria. Fifteen clinical trials (Lixilan and DUAL trial) were pooled and entered into review manager 5.4 and Graph Prism 8. [1,2,11–15,3–10] The primary endpoint was the mean difference in HbA1c and Fasting plasma glucose from baseline in each group; secondary efficacy endpoints were risk ratio of achievement of end-of-trial HbA1c of less than 7.0% and several participants without weight gain at the end of the trial. Safety variables included severe, non-serious adverse, and hypoglycaemic events. Results: Fifteen RCTs were identified using a total of 9896 T2DM patients i.e;5509 intervention and 4389 control. The baseline data of mean age respectively Lixilan vs DUAL in each case and control group was 58.2 ±1.92;58.2 ±1.92 in Lixilan Trial, while in DUAL trial 58.2 ±1.92 and 58.2 ±1.92; duration of diabetes 9.97±1.51; 10.2± 1.34 vs 9.46±2.13; 9.6±2.08 years, HbA1C (%) 8.11± 0.108; 8.09±0.12 vs 8.24±0.06;8.25±0.31; Fasting plasma glucose (mmol/L) 8.5±1.03; 8.52±1.03 vs 9.29±0.49; 9.39±0.56. Primary endpoint such as a decrease in HbA1c, FPG level, the proportion of HbA1c < 7%, and patient without weight gain was not different as statically with p=0.32;0,29,0.34;0.95. The safety endpoint showed the same result. Severe hypoglycaemia was 1.06 (0.48, 2.34). Discussion: Limitations: The assumptions made in the indirect comparison and differences between the included trials in efficacy and safety endpoint. Conclusion: These results, either efficacy and safety endpoint showed no statistically significant differences between IGlarLixi and IDegLira, and both states promising beneficial clinically with equal evidence.