Glucagon-like peptide-1 receptor agonists and gastric emptying time: a systematic review and meta-analysis of prospective studies

Abstract

Purpose: Current management of type 2 diabetes mellitus and obesity increasingly includes treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). In this systematic review and meta-analysis, we sought to characterize the effect of GLP-1 RAs on gastric emptying half-time (T½). Methods: We conducted a systematic review of prospective studies reporting T½ with and without GLP-1 RA treatment. Inclusion criteria were 1) patients aged ≥ 18 yr taking a GLP-1 RA for diabetes mellitus and/or weight loss, 2) gastric emptying assessment reported as emptying T½, and 3) study design that was a randomized controlled trial or a prospective cohort study. We searched the following databases: MEDLINE, MEDLINE In-Process/ePubs, Embase, Cochrane Central Register of Controlled Trials, American Psychological Association (APA) PsycInfo®, and CINAHL. We assessed the quality of the studies with the risk of bias assessment tool for randomized controlled trials and the Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) tool for nonrandomized trials. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification for assessment of the certainty of the evidence. We performed multilevel random effects meta-analysis to pool standardized mean differences. Results: We included 10 studies (N = 300), one of which reported two independent samples; these were treated as two independent studies for the purpose of meta-analysis. Glucagon-like peptide-1 receptor agonists significantly increased gastric emptying T½, with a large effect size (standardized mean difference, 2.38; 95% confidence interval [CI], 1.05 to 3.71; P < 0.001) corresponding to a mean prolongation of 74 min (95% CI, 46 to 101). There was a trend towards a more pronounced effect with short-acting GLP-1 RAs, with a standardized mean difference of 3.86 (95% CI, 2.37 to 5.35) corresponding to a prolongation of 116 min (95% CI, 71 to 161) and early treatment phases (< 10 weeks) with a standardized mean difference of 2.72 (95% CI, 1.15 to 4.35) with a mean prolongation of 82 min (95% CI, 35 to 131). Nevertheless, the certainty of the effect size following the GRADE classification was “very low.” Conclusions: In this systematic review and meta-analysis, we found that GLP-1 RAs significantly prolonged gastric emptying T½ by a mean of 74 min, which could have implications for perioperative care. There was a trend towards a more pronounced effect with short-acting (vs long-acting) drugs and in the early treatment phases (< 10 weeks). Study registration: PROSPERO (CRD42023461665); first submitted 8 September 2023.