The correlations between steady-state concentration, duration of action and molecular weight of GLP-1RAs and their efficacy and gastrointestinal side effects in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. (4th March 2023)

• Record Type: Journal Article
• Authors: Jiao, Ruoyang; Lin, Chu; Bai, Shuzhen; Cai, Xiaoling; Hu, Suiyuan; Lv, Fang; Yang, Wenjia; Zhu, Xingyun; Ji, Linong
• Is Part Of: Expert opinion on pharmacotherapy. Volume 24:Number 4(2023)
• Page Start: 511
• Page End: 521
• Publication Date: 2023-03-04
• Subjects: glucagon-like peptide-1 receptor -- type 2 diabetes -- glycemic control -- gastrointestinal side effect; Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1080/14656566.2023.2181693
• Languages: English
• ISSNs: 1465-6566

Abstract

ABSTRACT: Background: To assess the influence of steady-state concentration, duration of action and molecular weight of glucagon-like peptide-1 receptor (GLP-1RA) on efficacy and gastrointestinal (GI) side effects in patients with type 2 diabetes mellitus (T2DM). Methods: PubMed, EMBASE, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from inception to April 2022. Randomized controlled trials (RCTs) comparing GLP-1RA versus non-GLP-1RA agents in patients with T2DM were included. Sensitivity analyses on steady-state concentration, duration of action and molecular weight of GLP-1RA were conducted. Results: 113 RCTs were included. Greater HbA1c reduction between GLP-1RA users versus non-GLP-1RA users was observed in the high-steady-state-concentration stratum and long-acting stratum compared with the low-steady-state-concentration stratum (Psubgroup difference = 0.0004) and short-acting stratum (Psubgroup difference <0.0001). The risk of GI adverse events in GLP-1RA users versus non-GLP-1RA users was decreased in the high-steady-state-concentration stratum, long-acting stratum and heavy-molecular-weight stratum compared with low-steady-state-concentration stratum (Psubgroup difference <0.0001), short-acting stratum (Psubgroup difference = 0.002) and light-molecular-weight stratum (Psubgroup difference = 0.0008). Conclusion: GLP-1RA with high steady-state concentration and long duration of action showed better hypoglycemic effect. GLP-1RA with high steady-state concentration, long duration of action and heavy molecular weight was associated with lower risk of GI adverse events.