AUTHOR=Jung Han Na , Cho Yun Kyung , Min Se Hee , Kim Hwi Seung , Kim Ye-Jee , Park Joong-Yeol , Lee Woo Je , Jung Chang Hee 

TITLE=Free Versus Fixed-Ratio Combination of Basal Insulin and GLP-1 Receptor Agonists in Type 2 Diabetes Uncontrolled With GLP-1 Receptor Agonists: A Systematic Review and Indirect Treatment Comparison

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.870722

DOI=10.3389/fendo.2022.870722

ISSN=1664-2392

ABSTRACT=This study evaluates the efficacy and safety of the free up-titration of basal insulin and fixed-ratio combination (FRC) of basal insulin and glucagon-like peptide-1 receptor agonists (GLP-1RA) in type 2 diabetes mellitus (T2DM) patients inadequately controlled with GLP-1RA. With a systematic literature review in PubMed, Embase, Web of Science, and the Cochrane Library databases through July 2021, randomized controlled trials that compared the free up-titration or FRC with remaining on GLP-1RA in T2DM patients uncontrolled with GLP-1RA were included. A comparison of adding basal insulin to maintaining GLP-1RA and an indirect comparison between the two strategies was conducted on the change in HbA1c, fasting plasma glucose (FPG), target achievement [HbA1c <7.0%], and the risk of confirmed hypoglycemia. The Cochrane Collaboration’s tool was used to assess the risk of bias. Two free up-titration and two FRC trials involving 1,612 participants and all lasting 26 weeks were included. Both approaches significantly lowered HbA1c levels (weighted mean difference [WMD] −0.75%, 95% confidence interval [CI] −0.97 to −0.53) but increased hypoglycemic risk (relative risk [RR] 7.59, 95% CI 3.35−17.17) compared to the unchanged GLP-1RA. No significant differences were discovered between the two methods regarding the decrease in HbA1c (WMD 0.08%, 95% CI −1.07−1.23%), FPG (WMD −2.29 mg/dL, 95% CI −45.07−40.49 mg/dL), target achievement (RR 1.03, 95% CI 0.50−2.14), and hypoglycemic risk (RR 0.32, 95% CI 0.03−3.59). In patients who failed with GLP-1RA, both strategies of adding basal insulin, free up-titration and FRC are comparable options.