Table 5.
Summary of efficacy of other prokinetic agents (5-HT4 and ghrelin receptor agonists) on symptoms or gastric emptying (GE)
| Medication/trial design | N, Etiology | Dose (p.o.) | Duration | Efficacy | Reference |
|---|---|---|---|---|---|
| 5-HT4 agonists | |||||
| Clebopride PC, DB, RCT | 76 with dyspeptic syndromes and x-ray proven delayed GE | 0.5 mg tid | 3 months | Clebopride was more effective than placebo in reducing or relieving symptoms | Bavestrello 1985, ref. 87 |
| Prucalopride PC, DB, XO, RCT | 13 DM, 2 connective tissue disease | 4mg/day | Two 4-wk treatments with 2 wks washout | GE faster on prucalopride; GCSI scores were lower than baseline but not different between treatment arms. Meal-related symptom scores over time or cumulative score were not significantly different between groups. GE was more rapid in the prucalopride treatment period, | Andrews 2021, ref. 88 |
| Prucalopride PC, DB, XO, RCT | 28 IG, 6 DG | 2mg/day | Two 4-wk treatments with 2 wks washout | Prucalopride significantly improved the total GCSI, subscales of fullness/satiety, nausea/vomiting, and bloating/distention, overall PAC-QOL score and gastric emptying T1/2; also all efficacies were shown only in the idiopathic group | Carbone 2019, ref. 89 |
| Revexepride: PG, DB, PC, stratified, repeated dose RCT | 62 non-DM; 30 DM (55 female, 37 male); gastroparesis symptoms, and slower baseline GEBT T1/2 in placebo group | 0.02, 0.1, or 0.5 mg tid | 4 weeks | Large inter-individual differences in GEBT with no significant treatment effect; GCSI and PAGI-SYM scores decreased at Week 2 and decreased further at Week 4 in all groups including placebo. Quality of life improved in all treatment groups after 4 weeks of treatment. | Tack et al 2016, ref. 90 |
| Velusetrag: DB, PC, RCT; 3-period XO | 18 DG, 16 IG | 5, 15 or 30 mg po daily | 7 days each period | GE T1/2 numerically reduced with all 3 doses of velusetrag vs placebo. Efficacy was similar between subjects with diabetic and idiopathic gastroparesis. | Kuo 2021, ref. 91 |
| Felcisetrag: DB, PC, RCT | 36: 22 IG, 14 DG | 0.1, 0.3 or 1.0mg i.v., daily | 3 days | Felcisetrag significantly accelerated GE, small bowel transit, ascending colon emptying (T1/2) and colonic transit at 48 hours | Chedid 2021, ref. 92 |
| Ghrelin Agonist | |||||
| Relamorelin RCT, PC, XO | 10 T1DM with previous delayed GE | 100 μg SQ | Single dose | Decreased gastric retention of solids at 1h and 2h and decreased GCSI-DD scores and nausea/vomiting/fullness/pain scores | Shin 2013, ref. 93 |
| Relamorelin RCT, PC, PG | 204 DG + moderate to severe symptoms and delayed GE | 10 μg SQ daily or 10 μg SQ bid | 12 weeks | Relamorelin (10 μg bid) significantly accelerated GE and significantly reduced vomiting vs. placebo. Among patients with baseline vomiting, relamorelin accelerated GE, reduced vomiting and improved other symptoms | Lembo 2016, ref. 94 |
| Relamorelin RCT, PC, PG | 393 DM with moderate to severe gastroparesis symptoms | 10 μg, or 30 μg or 100 μg or placebo SQ bid | 12 weeks | 75% reduction in vomiting frequency vs baseline (NS compared with placebo). All 4 symptoms of DG (composite or individual symptoms) significantly reduced over 12-wk in all 3 relamorelin doses and accelerated GE vs. placebo. Adverse effect: impaired glycemic control with relamorelin | Camilleri 2017, ref. 95 |
| Relamorelin and TZP-101 or TZP 102: 6 RCTs in SRMA | DG (N=557) | Diverse doses | Significantly improved overall gastroparesis symptoms (standardized mean difference, −0.34; 95% CI, −0.56 to −0.13) and significantly improved symptoms, including nausea, vomiting, early satiety, and abdominal pain | Hong 2020, ref. 96 | |
| Motilin Agonists | |||||
| Erythromycin RCT, PC, XO | 10 T1DM | 200mg iv; 250mg p.o. tid | 4 weeks | Solid meal retention at 2h: 63±9% with placebo; 4±1% with erythromycin; no effects on the symptoms | Janssens 1990, ref. 97 |
| Erythromycin open trials of i.v. and p.o. | 10 IG and 4 DG; 4 patients dropped out | 6 mg/kg i.v. 500 mg tid-ac and qhs |
Single dose; 4 wk and open 8.4 mo |
Solid meal retention at 2h: 85±11% (SD) at baseline; 20±29% on iv erythromycin (p <0.001); 48±21% after 4 wk of oral therapy (p <0.01). Reduction in total symptom scores and a significant reduction in global assessment scores |
Richards 1993, ref. 98 |
| Erythromycin vs metoclopramide RCT, XO | 13 DG | p.o. 250 mg tid erythromycin; p.o.10 mg tid metoclopramide | 3 weeks each period | Compared with baseline, improved GE parameters after both erythromycin and metoclopramide, with improved total GI symptom scores, more pronounced with erythromycin | Erbas 1993, ref. 64 |
| Erythromycin RCT, PC, XO | 20 IG (functional dyspepsia + delayed GE) | 200mg i.v. | Single dose | Erythromycin accelerated (breath test) solid GE T½=146 (27) vs 72 (7) min, and liquid GE T½=87 (6) vs 63 (5) min; no overall symptom improvement except for bloating | Arts 2005, ref. 99 |
| Erythromyin vs azithromycin retrospective case-control analysis | 120 patients (27 DM) underwent SGE with provocative testing | 250mg i.v. of each drug | Single dose | Both treatments accelerated gastric emptying with no difference between the 2 treatments: erythromyin GE T½=166±68min baseline to 11.9±8.4min; azithromycin GE T½=178±77min baseline to 10.4±7.2min |
Larson 2010, ref. 100 |
DB=double-blind; DM=diabetic; DG=diabetic gastroparesis; GCSI=Gastroparesis Cardinal Symptom Index; GE=gastric emptying; GEBT=gastric emptying breath test; IG=idiopathic gastroparesis; i.v.=intravenous; N=number; NA=not available; PAC-QOL=patient assessment of constipation–quality of life; PAGI-SYM=patient assessment of upper gastrointestinal disorders–symptoms; PC=placebo-controlled; po=oral; PG=parallel-group; p.o.=oral; PSG=post-surgical gastroparesis; RCT=randomized, controlled trial; SGE=GE by scintigraphy; SQ=subcutaneous; SRMA=systematic review and meta-analysis; XO=crossover