Copyright ©The Author(s) 2019.
World J Gastroenterol. Mar 14, 2019; 25(10): 1185-1196
Published online Mar 14, 2019. doi: 10.3748/wjg.v25.i10.1185
Table 1 Commonly encountered gastrointestinal diseases and their phenotypic presentations (symptoms and pathophysiology) and management principles
Disease phenotypeSymptomsPathophysiologyDiagnosisTreatment options or selections
Functional dyspepsiaPostprandial fullness, early satiety; Epigastric pain, epigastric burningAlterations in gastric emptying and/or gastric accommodationGastric emptying study; Gastric accommodation studies (SPECT, MR imaging)Reduced GE and/or GA → prokinetic or gastric relaxants; Normal GE and GA → central pain modulator
Outlet dysfunction constipationConstipation, abdominal painPelvic floor dyssynergiaAnorectal manometry with balloon expulsion test; MR defecographyPelvic floor rehabilitation with biofeedback training
Slow transit constipationConstipation, abdominal painDecreased colonic motilityColon transit studies with radiopaque markers or scintigraphy or wireless motility capsuleProkinetic agents; Secretory + stimulant laxatives; Total colectomy with ileo-rectal anastomosis
Bile acid diarrheaDiarrhea; Abdominal painIncreased bile acid synthesis/ decreased bile acid absorptionTotal fecal bile acids; Fecal bile acid composition; Serum 7-α-hydroxy-4-cholesten-3-oneBile acid binders
Table 2 Pharmacological treatments (current or in-development) for indications based on accurate phenotyping of gastrointestinal disorders
DrugMechanism of actionIndicationTypical dosesPhases of trials completedStudy designImportant results
RelamorelinSynthetic ghrelin analogDiabetic gastro-paresis10 µg b.i.d. SQPhase 2 (Phase 3 on-going); Multicenter, randomized, double-blind, placebo-controlled, parallel-group study; 2 wk single-blind, placebo run-in[18]Diabetic gastroparesis patients (n = 393); Placebo (n = 104) vs relamorelin [10 µg (n = 98), 30 µg (n = 109), 100 µg (n = 82)] twice daily × 12 wkSymptoms of diabetic gastroparesis (but not vomiting frequency) significantly reduced vs placebo in all relamorelin groups; Significant acceleration of GE from baseline vs placebo; Dose-related worsening of glycemic control in relamorelin arm[18]
AcotiamideAcetyl-cholinesterase inhibitorFunctional dyspepsia100 mg t.i.d.Phase 3 Multicenter, single arm, open label safety trial[66]Functional Dyspepsia patients (n = 207); Acotiamide three times daily × 1 yrImproved postprandial fullness, early satiation, quality of life, work productivity; No significant adverse effects[66]
ColesevelamBile acid sequestrantsBAD625-1875mg b.i.d.FDA approved for DM2 and hyperlipidemia; Single center, unblinded single-dose trial in IBS with BAD[67]IBS-D with prior evidence of increased bile acid synthesis/excretion (n = 12): colesevelam 1875 mg twice daily × 10 dIncreased fecal total bile acid, and deoxycholic acid excretion by sequestration by BA binder; Increased serum C4; More solid stool consistency[67]
ColestipolBAD5 g daily initially, + 5 g/ mo increase up to 30 g dailyFDA approved for primary hypercholesterolemiaNo large trials for primary therapy in treatment of bile acid diarrhea[68]Can consider in those who do not tolerate colesevelam or cholestyramine[68]
Prucalopride5-HT4 receptor agonistCC1 mg (> 65 yr); 2 mg (< 65 yr) q.d.FDA approved; Multiple Phase 3: multicenter, randomized, placebo-controlled, parallel group trials[69]Chronic constipation patients (n = 620); Placebo vs prucalopride 2 mg vs prucalopride 4 mgSignificant increase in patients with three or more spontaneous, complete bowel movements/week with 2 mg prucalopride vs placebo NNT = 5[69]
TegaserodIBS-C and CC2 or 6mg bidFDA approved for patients with low cardiovascular risk; Multiple phase 3 and 4 trials with several; Systematic reviews and Meta-analyses showing consistent efficacy[70]9242 patients in 11 trials (3 only females, 8 studies with constipation predominant patients); Tegaserod 0.5-12 mg twice daily for 4 to 20 wkRelative risk of symptoms persisting = 0.85% (95%CI: 0.80-0.90, I2 = 57%); NNT = 10[70]
Alosetron5-HT3 receptor antagonistIBS-D0.5-1.0 mg b.i.d.FDA approved; Multiple phase 3 and 4 trials with several; Systematic reviews and Meta-analyses showing consistent efficacy[70]4987 IBS patients in 8 trials (5 with only female participants); Alosetron (dose range studied 0.1 to 8 mg) twice daily compared to placeboRelative risk of symptoms persisting = 0.79; (95%CI: 0.69-0.90, I2 = 85%) NNT = 8[70]