Efficacy and Safety of Ghrelin Agonists in Patients with Diabetic Gastroparesis: A Systematic Review and Meta-Analysis
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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 I2 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.
Abstract
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 I2 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.
참고문헌 (38)
- Camilleri M, "Epidemiology, mechanisms, and management of diabetic gastroparesis", Clin Gastroenterol Hepatol, 9, pp.5~12 (2011)
- Nanlong Liu, "Gastroparesis Updates on Pathogenesis and Management", Gut and Liver, 11(5), pp.579~589 (2017), 거트앤리버 소화기연관학회협의회
- Choung RS, "Risk of gastroparesis in subjects with type 1and 2 diabetes in the general population", Am J Gastroenterol, 107, pp.82~88 (2012)
- Camilleri M, "American College of Gastroenterology", Clinical guideline: management of gastroparesis, 108, pp.18~37 (2013)
- Kumar M, "The investigation and treatment of diabetic gastroparesis", Clin Ther, 40, pp.850~861 (2018)
- Camilleri M, "Actions and therapeutic pathways of ghrelin for gastrointestinal disorders", Nat Rev Gastroenterol Hepatol, 6, pp.343~352 (2009)
- Dass NB, "Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin", Neuroscience, 120, pp.443~453 (2003)
- Xu L, "Evidence for the presence of motilin, ghrelin, and the motilin and ghrelin receptor in neurons of the myenteric plexus", Regul Pept, 124, pp.119~125 (2005)
- Avau B, "Ghrelin signaling in the gut, its physiological properties, and therapeutic potential", Neurogastroenterol Motil, 25, pp.720~732 (2013)
- Van der Ploeg L, "Preclinical gastrointestinal prokinetic efficacy and endocrine effects of the ghrelin mimetic RM-131", Life Sci, 109, pp.20~29 (2014)
- Lasseter KC, "Ghrelin agonist(TZP-101) : safety, pharmacokinetics and pharmacodynamic evaluation in healthy volunteers : a phase I, first-in-human study", J Clin Pharmacol, 48, pp.193~202 (2008)
- Fraser GL, "Pharmacological demarcation of the growth hormone, gut motility and feeding effects of ghrelin using a novel ghrelin receptor agonist", Endocrinology, 149, pp.6280~6288 (2008)
- Ejskjaer N, "Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis : a randomized, placebo-controlled study", Neurogastroenterol Motil, 22, pp.e1069~e1281 (2010)
- Ejskjaer N, "A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis", Neurogastroenterol Motil, 25, pp.e140~e150 (2013)
- McCallum RW, "Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis", Neurogastroenterol Motil, 25, pp.e705~ (2013)
- Shin A, "Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying : pharmacokinetics and pharmacodynamics", Diabetes Care, 36, pp.41~48 (2013)
- Lembo A, "Relamorelin reduces vomiting frequency and severity and accelerates gastric emptying in adults with diabetic gastroparesis", Gastroenterology, 151, pp.87~96 (2016)
- Camilleri M, "Efficacy and safety of relamorelin in diabetics with symptoms of gastroparesis : a randomized, placebo-controlled study", Gastroenterology, 153, pp.1240~1250 (2017)
- Liberati A, "The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions : explanation and elaboration", BMJ, 339, pp.b2700~ (2009)
- Higgins JP, "The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials", BMJ, 343, pp.d5928~ (2011)
- Revicki DA, "Gastroparesis Cardinal Symptom Index(GCSI) : development and validation of a patient reported assessment of severity of gastroparesis symptoms", Qual Life Res, 13, pp.833~844 (2004)
- Rentz AM, "Development and psychometric evaluation of the Patient Assessment of Upper Gastrointestinal Symptom Severity Index(PAGI-SYM)in patients with upper gastrointestinal disorders", Qual Life Res, 13, pp.1737~1749 (2004)
- Revicki DA, "Evaluating symptom outcomes in gastroparesis clinical trials : validity and responsiveness of the Gastroparesis Cardinal Symptom Index-Daily Diary(GCSI-DD)", Neurogastroenterol Motil, 24, pp.456~463 (2012)
- Shin A, "The ghrelin agonist RM-131accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus", Clin Gastroenterol Hepatol, 11, pp.1453~1459 (2013)
- Janssen P, "The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis", Am J Gastroenterol, 108, pp.1382~1391 (2013)
- Kumar A, "Visceral hypersensitivity and impaired accommodation in refractory diabetic gastroparesis", Neurogastroenterol Motil, 20, pp.635~642 (2008)
- Tack J, "Pathophysiology and treatment of functional dyspepsia", Gastroenterology, 127, pp.1239~1255 (2004)
- Khayyam U, "Assessment of symptoms during gastric emptying scintigraphy to correlate symptoms to delayed gastric emptying", Neurogastroenterol Motil, 22, pp.539~545 (2010)
- Enck P, "Functional dyspepsia", Nat Rev Dis Primers, 3, pp.17081~ (2017)
- Tack J, "Gastroduodenal motility disorders", Curr Opin Gastroenterol, 34, pp.428~435 (2018)
- Ang D, "Influence of ghrelin on the gastric accommodation reflex and on meal-induced satiety in man", Neurogastroenterol Motil, 21, pp.528~533 (2009)
- Mao Y, "Antinociceptive effect of ghrelin in a rat model of irritable bowel syndrome involves TRPV1", Opioid systems, 2017, pp.43, 518~530
- Iovino P, "Bloating and functional gastro-intestinal disorders : where are we and where are we going", World J Gastroenterol, 20, pp.14407~14419 (2014)
- Murray CD, "Ghrelin enhances gastric emptying in diabetic gastroparesis : a double blind, placebo controlled, crossover study", Gut, 54, pp.1693~1698 (2005)
- Ejskjaer N, "Ghrelin receptor agonist(TZP-101)accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis", Aliment Pharmacol Ther, 29, pp.1179~1187 (2009)
- Wo JM, "Randomised clinical trial : ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting--randomised clinical study subset data", Aliment Pharmacol Ther, 33, pp.679~688 (2011)
- Swerdlow AJ, "Cancer risks in patients treated with growth hormone in childhood : the SAGhE European Cohort Study", J Clin Endocrinol Metab, 102, pp.1661~1672 (2017)
- Sever S, "Is there an effect of ghrelin", ghrelin analogs on cancer? A systematic review, 2016, pp.23, R393~R409