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Meta-Analysis
. 2023 Mar;11(2):146-162.
doi: 10.1002/ueg2.12362. Epub 2023 Jan 30.

Do prokinetic agents provide symptom relief through acceleration of gastric emptying? An update and revision of the existing evidence

Nick Goelen  1 , Mike Jones  2 , I-Hsuan Huang  1 , Florenca Carbone  3 , Pieter Janssen  1 , Jan Tack  1   3
Affiliations
Meta-Analysis

Do prokinetic agents provide symptom relief through acceleration of gastric emptying? An update and revision of the existing evidence

Nick Goelen et al. United European Gastroenterol J. 2023 Mar.

Abstract

Background: Gastroparesis and functional dyspepsia are disorders characterized by upper gastrointestinal symptoms and multifaceted etiologies. One of the main therapeutic approaches is accelerating gastric emptying (GE) by means of prokinetic agents. Their efficacy has been demonstrated, although the association between symptom improvement and acceleration of emptying is less clear. Meta-analyses have found contradictory results. Differences in applied methodology and included trials might drive these contradictions.

Objective: To provide a transparent meta-analysis update to elucidate the association between symptom improvement and acceleration of GE due to gastroprokinetic agents available for long-term use in patients with gastroparesis.

Design: Two approaches from earlier meta-analyses were executed and compared. One analyzed the relative changes on active treatment versus baseline, the other compared the change from baseline on active treatment versus the change from baseline on placebo. Papers that reported sufficient numerical data for both analyses were selected. Both analyses included the same trials.

Results: Overall, both approaches yield the same positive direction of association between symptom improvement and acceleration of emptying (0.291 (-0.391, 0.972), p = 0.4 and 0.453 (0.123, 0.782), p = 0.007 for the active-only and placebo-controlled analysis respectively). The association between symptom improvement and GE acceleration for studies using optimal GE tests was either 0.028 (p > 0.9) or 0.463 (p = 0.007), and for sub-optimal GE tests was either 0.370 (p = 0.4) or 0.052 (p > 0.9) depending on the used meta-analysis methodology.

Conclusions: The applied methodology for GE testing, and the meta-analysis substantially impacts the conclusion. When considering the clinically relevant outcome of improvement from baseline, symptoms and emptying improve with prokinetics, but no correlation is found between both aspects. When the change over placebo is considered, limiting the analysis to scientifically more rigorous study approaches, changes in emptying rate and symptom improvement are positively associated.

Keywords: botulinum toxin; buspirone; cisapride; domperidone; erythromycin; gastric emptying; gastroparesis; ghrelin; levosulpiride; metoclopramide; prokinetic.

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Conflict of interest statement

Jan Tack has given Scientific advice to Adare, AlfaWassermann, Arena, Bayer, Christian Hansen, Clasado, Danone, Devintec, Falk, FitForMe, Grünenthal, Ironwood, Janssen, Kiowa Kirin, Menarini, Mylan, Neurogastrx, Neutec, Novartis, Nutricia, Reckitt Benckiser, Ricordati, Shionogi, Takeda, Truvion, Tsumura, Zealand and Zeria pharmaceuticals, has received research support from Biohit, Shire, Sofar and Takeda, and has served on the Speaker bureau for Abbott, Allergan, AstraZeneca, FitForMe, Janssen, Kyowa Kirin, Mayoly, Menarini, Mylan, Novartis, Schwabe Parmaceuticals, Takeda, Wellspect and Zeria.

Figures

FIGURE 1
FIGURE 1
Identification of studies included in the analysis.
FIGURE 2
FIGURE 2
Funnel plot of Egger's test. The vertical and diagonal lines respectively represent the pooled effect size and its 95% confidence interval boundaries.
FIGURE 3
FIGURE 3
Scatter plot with regression line of the association between symptom change (negative = reduction in symptom burden) and change in gastric half‐emptying time (negative = faster emptying), both expressed as standardized mean differences (SMD). Label numbers correspond with Forest plot.
FIGURE 4
FIGURE 4
Forest plot of change in gastric symptom score expressed as standardized mean differences (SMD). Negative values indicate lower symptom burden compared to baseline. Weights for regression model are shown. Reference numbers are unique for single data entries.
FIGURE 5
FIGURE 5
Forest plot of change in gastric symptom score, stratified by robustness of gastric emptying (GE) test methodology (optimal vs. sub‐optimal). Change in symptom scores expressed as standardized mean differences (SMD). Negative values indicate lower symptom burden compared to baseline. Weights for regression model are shown. Reference numbers are unique for single data entries.
FIGURE 6
FIGURE 6
Forest plot of change in gastric symptom score, stratified by study design. Negative values indicate lower symptom burden compared to baseline. Weights for regression model are shown. Reference numbers are unique for single data entries.
FIGURE 7
FIGURE 7
Forest plot of change in gastric symptom score, stratified by main mechanism of action of the therapeutic agent (centrally vs. not centrally acting). Negative values indicate lower symptom burden compared to baseline. Weights for regression model are shown. Reference numbers are unique for single data entries.
FIGURE 8
FIGURE 8
Forest plot of percentage change in gastric symptom score relative to baseline. Negative values indicate lower symptom burden compared to baseline. Weights for regression model are shown. Reference numbers are unique for single data entries
FIGURE 9
FIGURE 9
Scatter plot with regression line of the association between symptom change (negative = reduction in symptom burden) and change in gastric half‐emptying time (negative = faster emptying), both expressed as percentage change in the active group of each trial. Label numbers correspond with Forest plot.
See this image and copyright information in PMC

Comment in

  • Gastric emptying rate and relevance for symptoms.
    Törnblom H. Törnblom H. United European Gastroenterol J. 2023 Apr;11(3):269-270. doi: 10.1002/ueg2.12379. Epub 2023 Mar 14. United European Gastroenterol J. 2023. PMID: 36918964 Free PMC article. No abstract available.

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