Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. GLP-2 (Teduglutide)

   human RCT Direct outcome Approved for this condition

   Who was studied

   adults with short bowel syndrome dependent on parenteral support for at least 12 months, n=86 randomised 1:1, mean age 50 years, mean remaining small intestine 77.3 +/- 64.4 cm, 24 weeks; a separate 24-week study enrolled 59 children aged 1 to 17 years, 26 of them at the licensed dose. Sex breakdown is not given in the label

   Approved by the FDA as GATTEX for adults and children aged 1 year and older with short bowel syndrome who are dependent on parenteral support. The registrational endpoint was a fall of at least 20% in weekly parenteral nutrition volume at both week 20 and week 24, reached by 63% (27/43) on teduglutide against 30% (13/43) on placebo (p=0.002); mean weekly volume fell 4.4 L from a baseline of 12.9 L against 2.3 L from 13.2 L. Ten of the 30 patients who completed 30 months in the open-label extension came off parenteral support altogether, which was not an endpoint of the randomised study.

   Source DailyMed — the FDA label 1 primary source read for this row

2. hGH

   human RCT Direct outcome Approved for this condition

   Who was studied

   adults with short bowel syndrome dependent on intravenous parenteral nutrition, n=41 in three arms (placebo plus glutamine n=9, somatropin without glutamine n=16, somatropin with glutamine n=16); two-week equilibration then four weeks of double-blind treatment; sex not reported in the label

   Recombinant human growth hormone is approved by the FDA as Zorbtive (somatropin, rDNA origin) for short bowel syndrome in patients receiving specialised nutritional support. The primary endpoint was change in weekly total intravenous parenteral nutrition volume after four weeks at about 0.1 mg/kg/day: a mean fall of 3.8 L/week on placebo plus glutamine, 5.9 L/week on somatropin alone and 7.7 L/week on somatropin with glutamine. The label states that administration for more than 4 weeks has not been adequately studied and that safety and effectiveness in paediatric patients with short bowel syndrome have not been established; peripheral oedema was reported in 69% and 81% of the two somatropin arms against 11% on placebo.

   Source FDA label 1 primary source read for this row

3. GLP-1 (7-36)

   human observational Surrogate marker Not approved for this condition

   Who was studied

   adults with short bowel syndrome, n=9 (5 women, 4 men), aged 52 +/- 11 years, 7 with end-jejunostomy and 2 with half the colon in continuity; four 72-hour balance studies per patient

   Each patient completed four identical 72-hour balance studies receiving continuous intravenous GLP-1, saline placebo, GLP-2, or GLP-1 plus GLP-2 at 1 pmol/kg/min. GLP-1 lowered faecal wet weight, energy, nitrogen, sodium and potassium losses against placebo, but only the GLP-2-containing arms raised absolute wet weight and sodium absorption, and the authors concluded GLP-1 was the less potent of the two. Graded as observational rather than as a randomised trial because the abstract calls the study placebo-controlled without stating that treatment order was randomised or that anyone was blinded, and the full text is subscription-only; the abstract also names the infusate only as GLP-1, without specifying the 7-36 amide form. Acute balance-study absorption is not parenteral support volume or dependency, neither of which was measured.

   Source PubMed 1 primary source read for this row

4. Exendin-4

   human case series Direct outcome Not approved for this condition

   Who was studied

   5 consecutive patients with 90 cm or less of remaining small bowel, 4 men and 1 woman, aged 46 to 69 years, one month of treatment, no control group

   Exenatide is the synthetic form of exendin-4. In an uncontrolled series of five patients, all of whom had 6 to 15 bowel movements a day at baseline, bowel frequency and stool form improved and total parenteral nutrition was stopped in three of the five within a month; fasting antroduodenal manometry normalised. There was no control group, no randomisation and no blinding, the whole series is five people, and no larger or controlled study of exenatide in short bowel syndrome is on file.

   Source PubMed 1 primary source read for this row

5. Liraglutide

   human case series Surrogate marker Not approved for this condition

   Who was studied

   adults with end-jejunostomy short bowel syndrome and intestinal failure, n=8, aged 63.4 +/- 10.9 years, remaining small bowel 110 +/- 66 cm, 8 weeks open-label, no control group; sex not reported in the abstract

   An 8-week open-label pilot study ran 72-hour metabolic balance studies before and after once-daily subcutaneous liraglutide. Ostomy wet weight output fell by 474 +/- 563 g/day from 3249 +/- 1352 g/day (p=0.049) and intestinal energy absorption rose by 902 +/- 882 kJ/day (p=0.02). Parenteral support volume and oral fluid intake were deliberately held constant throughout, so no change in parenteral support requirement was or could be measured; the authors describe the result as a hypothesis for larger randomised placebo-controlled studies, and no such study is on file.

   Source PubMed 1 primary source read for this row

6. BPC-157

   animal in vivo Surrogate marker Not approved for this condition

   Who was studied

   rats with surgically induced short bowel syndrome after resection from the fourth ileal artery to 5 cm below the pylorus, followed 4 weeks; strain, sex and n per group not reported in the abstract obtained

   BPC 157 at 10 mcg/kg or 10 ng/kg, given intraperitoneally or in drinking water for 4 weeks, was reported to reverse postoperative weight loss and to change villus height, crypt depth, muscular layer thickness, the jejunum-to-ileum diameter ratio and anastomosis breaking strength. Those are adaptation morphology in a rat, not absorption or parenteral support in a person. No human study of BPC-157 in short bowel syndrome exists: the phase II inflammatory bowel disease programme the paper cites (PL 14736, Pliva) has no published result, and ClinicalTrials.gov lists three registered BPC-157 studies - healthy volunteers, hamstring strain and a peptide gummy - none with a gastrointestinal endpoint.

   Source PubMed 2 primary sources read for this row

Checked, and nothing recorded

20 compounds were checked against short bowel syndrome and produced no gradeable row.

• Carnosine — checked, no row on file
• Cholecystokinin (CCK) — checked, no row on file
• Dulaglutide — checked, no row on file
• Galanin — checked, no row on file
• Gastrin — checked, no row on file
• Ghrelin — checked, no row on file
• GIP (Gastric Inhibitory Peptide) — checked, no row on file
• Guanylin — checked, no row on file
• Ipamorelin — checked, no row on file
• KPV — checked, no row on file
• Motilin — checked, no row on file
• Neurotensin — checked, no row on file
• Omentin — checked, no row on file
• PEA — checked, no row on file
• PYY3-36 — checked, no row on file
• Secretin — checked, no row on file
• Semaglutide — checked, no row on file
• Uroguanylin — checked, no row on file
• VIP — checked, no row on file
• Wheat Peptides — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.