Is GLP2 Worth $300K per Year?

E Ramos Boluda et al. JPGN 2020; 71: 734-739. Experience With Teduglutide in Pediatric Short Bowel Syndrome: First Real-life Data

S Hill. JPGN 2020; 71: 697-698 (editorial) Use of GLP-2 May Herald a New Era of Improved Outcome of Short Bowel Syndrome-associated Intestinal Failure

The study and associated editorial highlight the effectiveness of GLP-2 in a prospective cohort of 17 patients with short bowel syndrome. It is noted that Dr. Hill has received funding from the pharmaceutical manufacturer of the product.

Key findings:

  •  A total of 12 of 17 patients achieved parenteral independence: 3 patients after 3 months of treatment, 4 patients at 6 months, and 5 after 12 months.
  • The percentage able to wean off parenteral nutrition was 17%, 44%, and 60% at 3, 6, and 12 months respectively. Only 1 patient did not exhibit improvement
  • Plasma citrulline levels, a marker for enteral autonomy, increased from a baseline average of 20 micromol/l to 37.5, 46.75, and37.9at 3, 6, and 12 months respectively.
  • Adverse reactions included abdominal pain 30%, nauseas 18%, injection-site reactions 22%, and headache 16%.

Both the editorial and the study comment briefly on the cost of the therapy. The editorial also notes the current recommendation for surveillance endoscopy in view of a hypothetical risk of malignancy.

My take: Is GLP2 Worth the Cost? It probably depends on who is paying and long-term safety data. Perhaps, we will develop tools to improve prediction of which patients will achieve enteral autonomy with GLP2 who would otherwise require ongoing parenteral nutrition.

Related blog posts:

FDA News: FDA Warning for FMT, IB-Stim Device Approval, Teduglutide Approval

1.From John Pohl Twitter Feed:  FDA Warns of One Death Linked to Fecal Transplants (6/13/19)

An excerpt:

The consent should include, at a minimum, a statement that the use of FMT to treat C. difficile is investigational and a discussion of its potential risks.

“Two immunocompromised adults who received investigational FMT developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli). One of the individuals died,” the agency said Thursday…

Openbiome, a nonprofit stool bank based in Cambridge, MA, told Focus: “We are saddened to hear of the recent patient death due to an infection from a multi-drug resistant organism (MDRO) transmitted through a fecal transplant. OpenBiome material was not involved. OpenBiome screens its donors and fecal transplant material for MDROs and related risk factors, and this serious event further highlights the importance of rigorous screening and clinical oversight for all fecal transplant procedures.”

 2. FDA approval for IB-stim (a.k.a. Neuro-stim) device.

Link:: FDA permits marketing of first medical device for relief of pain associated with irritable bowel syndrome in patients 11-18 years of age

An excerpt:

IB-Stim treatment resulted in at least a 30% decrease in usual pain at the end of three weeks in 52% of treated patients compared to 30% of patients who received the placebo, and at least a 30% decrease in worst pain in 59% of treated patients compared with 26% of patients who received the placebo.

:Kovacic K1Hainsworth K2Sood M1Chelimsky G1Unteutsch R1Nugent M3Simpson P3Miranda A4. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.

Link to abstract of relevant study:  Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial.

3. FDA Approves Gattex (Teduglutide) for Pediatric SBS

From CenterWatch: Gattex New FDA Drug Approval

Pediatric SBS: “In a 24-week pediatric study 59 pediatric patients with SBS aged 1 year through 17 years chose whether to receive Gattex or standard of care (SOC)…Based on patient-diary data, patients who received Gattex 0.05 mg/kg/day experienced a 42% mean reduction in PS volume (mL/kg/day) from baseline (-23 mL/kg/day from baseline). At week 24, 38% of patients (10/26) were able to reduce PS infusion by at least 1 day per week. Patients reduced their PS infusion time by 3 hours per day on average compared to baseline.”

Related blog post: Teduglutide for SBS

Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL, O’keefe SJ, Forbes A, Heinze H, Joelsson B Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology 2012 Dec;143(6):1473-1481

Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O’Keefe SJ Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut 2011 Jul;60(7):902-14.

#NASPGHAN17 Annual Meeting Notes (Part 2): Year in Review

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

This first slide shows the growth in NASPGHAN membership:

Year in Review

Melvin Heyman  Editor, JPGN

This lecture reviewed a number of influential studies that have been published in the past year.  After brief review of the study, Dr. Heyman summarized the key take-home point.


Nutrition Week (Day 4) Trophic Hormone for Pediatric Short Bowel Syndrome

A recent study (BA Carter et al. J Pediatr 2017; 181: 102-11) provides some preliminary data on the use of glucagon-like peptide-2 (GLP-2) (Teduglutide) for pediatric short bowel syndrome (SBS).

This was a 12-week, open-label study in patients aged 1-17 years with intestinal failure (IF) associated with SBS. Prior to the study, patients had shown little to minimal advance in enteral nutrition for at least 3 months. Three doses of GLP-2 (0.0125 mg/kg/d, 0.025 mg/kg/day, and 0.05 mg/kg/day).

Key findings:

  • All treated patients (37) experienced mild or moderate adverse effects, including vomiting, pyrexia, catheter-related complications, and upper respiratory tract infections. No serious adverse events were identified. In the 5 patients who received standard care, adverse effects were recorded as well, including upper respiratory tract infections in 2 (40%) which was similar to the other groups.
  • By week 12, parenteral nutrition (PN) volume and calories were reduced in the higher dosed groups.  In the 0.025 mg/kg/day group, PN volume dropped by 41% and calories by 45%.  In the 0.05 mg/kg/day group, PN volume dropped by 25% and calories by 52%. Virtually no change in these parameters occurred in the lowest dose (0.0125 mg/kg/day) with no change in volume and 6% drop in calories.
  • Enteral feeding volume occurred in all groups: 22%, 32%, and 40% in the groups and was directly related to the GLP-2 dosing.
  • Citrulline levels (a biomarker of enteral autonomy) were monitored “but the results were clouded by wide variability of baseline values.”  In adult studies, citrulline levels increased significantly.

My take: This open-label study has many limitations; further studies are planned (, NCT02682381). Nevertheless, this study indicates that GLP-2 holds promise as a therapy for SBS/IF.

Another slide in a recent lecture on PNALD (slide derived from Conrad Cole lecture in Octobler 2015 -available at Pediatric Nutritionist Blog, slide 49):


Related blog posts:

Four advances for intestinal failure

Several advances in the management of intestinal failure have the potential to improve the outlook for our intestinal failure (IF) (aka Short Bowel Syndrome) patients (JPEN 2012; 36: 36S-42S).

Although IF patients already have improving survival with rates of 80-95% over followup ranging from 1-5 years, many still do not survive, primarily due to bacterial infections or chronic liver disease.  Ongoing research has made some promising steps in the management of these pediatric patients.  This article focuses on four of these steps.

1. Citrulline monitoring

  • Major source of citrulline is enterocyte production.  Citrulline is an amino acid not encoded in human genetic code; it is present in some proteins as a product of posttranslational modification.
  • Watermelon is one of few dietary sources.
  • Useful biomarker for bowel length/absorption –independent of inflammatory markers
  • Levels >15-20 μmol/L indicate good likelihood of achieving enteral autonomy
  • Levels <12μmol/L indicate a very low likelihood of achieving enteral autonomy

2. Teduglutide therapy

  • Analog of glucagon-like peptide 2 (GLP-2) but harder to degrade (longer half-life)
  • Preliminary studies in adults indicate improvement in absorption and villous histology after subcutaneous administration for three weeks.  Improvements reverse when drug is discontinued.
  • Since GLP-2 is produced by colon & increased in IF (if colon present), unclear whether exogenous administration will be as beneficial in patients with residual colon

3. Lipid minimization &/or fish oil lipids

  • Cholestasis increases in patients receiving more than 1 g/kg/day of intralipids (soy based).
  • Fish oil (Omegaven) has shown benefit in lowering cholestasis in numerous case reports.  This may be due the high content of anti-inflammatory ω-3 fatty acids.
  • Another preparation SMOFLipid is a mixed formulation and may be safer than pure fish oil; randomized controlled studies of both of these lipid formulations are underway.
  • Fish oil has not been shown to improve histology
  • Parenteral nutrition associated liver disease (PNALD) may improve with lowering lipids & may not need omegaven

4. Ethanol locks

  • May be beneficial in treating and preventing central line infections.  In both situations, in small studies, ethanol locks lowered incidence of recurrent infections.
  • Six studies involving 75 patients (66 pediatric patients) lowered infection rates from approximately 10 per 1000 catheter days to 2 per 1000 catheter days.
  • Ethanol concentrations were mostly 70% in these studies, though 25% has been used.
  • Dwell times ranged from 2-14 hours.
  • Randomized studies are in progress.
  • Fewer infections should reduce the likelihood of death from sepsis and death due to loss of venous access.

Additional references:

  • -NEJM 2010; 362: 181.  Letter to editor describes use of fish oil in (n=125) Boston pediatric patients.
  • -JPGN 2009; 48: 209. n=12. SBS.9/12 improved with omegaven. 3 had transplant (L-ITx). No controls.
  • -NEJM 2009; 361: 998. Intestinal Rx.  Review claims ~90% 1yr survival. 47% 5yr, 61% 3yr (expecting to go higher)
  • -JPGN 2009; 48: 334. Isolated liver w SBS feasible IF 50cm small bowel remaining or 30cm w ICV, 50% enteral nutrition >4 weeks with good growth, no dysmotility.
  • -Pediatrics 2008; 121: e678. n=18. use of fish oil improved cholestasis compared to historical controls.
  • -Gastroenterology 2008; 135: 61, 303. Survival of ITx (vs. HAL).  In many conditions, better off from survival standpoint without Tx. Tx if failure of TPN (severe liver dz/thrombosis of >/= 2 central veins, multiple bouts of sepsis/frequent dehydration), high risk of death, severe short bowel (<10cm in infants and <20cm in adults), pseudoobstruction, unwillingness to accept long-term tpn. 93% of TPN patients who did not have TPN-complications had 93% survival rate.  Thus, TPN is first line Rx as survival and quality of life often better.
  • -Pediatrics 2006; 118: e197-e201.  Reversal of TPN-AC c IV omega-3 fatty acids (fish oil-derived) instead of intralipids
  • -Liver Transplantation 2006; 12: 1062, 1040. Liver transplant alone reasonable to consider in some SBS patients who tolerate >50% enteral therapy and are less than 2 years old.
  • -Gastroenterology 2006; 130. Supp 1. Summary of NIH workshop on intestinal failure. TX Indications: Liver disease, thrombosis of major veins, recurrent catheter-related sepsis, frequent severe dehydration/electrolyte imbalance.
  • -JPGN 2005; 41: 47A (pg507). Poor prognosis: <40cm, needing >40kcal/kg PN, increased bili (>150 μmol/L)
  • -J Pediatr 2005; 146: 542. Serum citrulline > 19 μ/L associated with bowel adaptation/weaning off HAL.
  • -J Pediatr 2004; 145: 157-163. Survival of SBS with as little as 15
  • -Arch Pediatr Adolesc Med 2006; 160: 104953.  Use of ethanol lock (70%, 08-1.4mL for 12-24hrs, then withdraw). n=51.  High success rate in salvaging line
  • -J Pediatr 2001; 139: 27-33. Review of 30 pts. 3 of 30 pts with bowel length 40cm or less able to wean PN.
  • -Gastroenterology 2001; 120: 806-815. Glucagon-like peptide 2 improves nutrient absorption marginally.