Efficacy and Safety of Ghrelin Agonists in Patients with Diabetic Gastroparesis: A Systematic Review and Meta-Analysis

Background/Aims: Ghrelin agonists are emerging prokinetic agents for treating gastroparesis. Although recent clinical trials have demonstrated their efficacy in patients with diabetic gastroparesis (DG), the impact of such agents on symptoms and gastric dysmotility remains unclear. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ghrelin agonists in patients with DG. Methods: A search of common electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) was preformed, using keyword combinations that referenced ghrelin and DG and retrieving all eligible randomized controlled trials (RCTs) of ghrelin agonists versus placebo in patients with DG. The primary outcome measure was the change in patient-reported overall gastroparesis symptom scores. Secondary outcomes included the change in gastric emptying time, specific symptoms related to gastroparesis, and adverse events. A random-effects model was applied to all study outcomes. Heterogeneity among studies was determined by the chi-square test and I-2 statistics. Results: We selected six RCTs of patients with DG (n=557) for meta-analysis. Ghrelin agonist administration (vs placebo) significantly improved overall gastroparesis symptoms (standardized mean difference, -0.34; 95% confidence interval, -0.56 to -0.13) and significantly improved symptoms related to gastroparesis, including nausea, vomiting, early satiety, and abdominal pain. Adverse events recorded for ghrelin agonists and placebo did not differ significantly. There was no significant heterogeneity among eligible studies. Conclusions: Compared with placebo, ghrelin agonists are effective and well-tolerated for the treatment of DG.