Peptide education
Apraglutide
Apraglutide is an investigational GLP-2 analog studied in adults whose short bowel syndrome causes intestinal failure. Its trials have examined whether the remaining intestine can absorb enough to reduce intravenous support.
In a phase 3 trial, weekly parenteral support volume fell more with apraglutide than placebo. A second phase 3 trial is registered to confirm the findings, and the drug remains investigational.
Overview
Quick answer
Short bowel syndrome does not always require intravenous support. The STARS trial enrolled people with intestinal failure who did require that support.
What is apraglutide being studied for?
The main clinical program studies short bowel syndrome with intestinal failure, where people depend on parenteral fluids, nutrition, or both. The goal is to reduce that support when absorption improves.
What did the main trial find?
Among 163 adults in STARS, average weekly support volume fell by 25.5% with apraglutide and 12.5% with placebo at week 24. The result describes a group average, not an individual response.
Is it approved?
Apraglutide remains investigational. The developer reported that another phase 3 trial was needed to seek US approval; STARS-2 is registered as a confirmatory study.
How was it administered in the studies?
STARS planned weekly subcutaneous doses of 5 mg for participants weighing at least 50 kg and 2.5 mg for those under 50 kg. The sponsor later reported lower delivered doses than planned. A separate phase 2 study tested 5 mg weekly and then a 10 mg treatment period.
Evidence
Evidence snapshot
At week 24, mean volume changed by -25.5% with apraglutide versus -12.5% with placebo in STARS.
At week 24, 43.0% of treated patients and 27.5% of placebo patients had at least one additional day per week without support.
At week 48, differences in days off support and complete independence in this subgroup were not statistically significant.
STARS-2 is a separate registered study. The sponsor reported that the FDA indicated a confirmatory phase 3 trial was needed to seek approval.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| Apraglutide can reduce the amount of parenteral support required. | The STARS trial found a greater average reduction in weekly support volume with apraglutide than with placebo at week 24. | Supported for the trial population and measured outcome. The drug remains investigational, and response varies. |
| Everyone taking apraglutide can stop intravenous support. | The main study measured changes in volume and support days. Complete independence was not achieved by all participants, and the week 48 colon-in-continuity comparison was not statistically significant. | No. Reduced volume, fewer support days, and complete independence are distinct outcomes. |
| A planned study dose always equals the amount delivered. | The sponsor reported that preparation and administration resulted in lower exposure and delivered doses than planned in STARS. | The distinction matters when interpreting this trial and later studies. |
Bottom line
Main takeaway
Apraglutide is being tested for people who need intravenous support because their remaining intestine cannot absorb enough fluid or nutrients.
Less support volume may reduce treatment burden, but it is not the same as coming off support completely.
The phase 3 primary endpoint favored apraglutide, while two key colon-in-continuity comparisons at week 48 did not reach significance.
Identity
What it is
Apraglutide acts on the GLP-2 pathway, which is involved in intestinal adaptation. It is distinct from GLP-1 drugs studied for metabolic disease.
Parenteral support can provide fluids or nutrients through a vein when the intestine cannot absorb enough. Clinical trials measured how support needs changed under a defined monitoring protocol.
Use context
Routes, doses, and cycle patterns
STARS used weekly injections and measured changes in parenteral support. Treatment and support adjustments occurred within a clinical trial.
Human studies and product labels
STARS phase 3
- Context
- Adults with short bowel syndrome and intestinal failure
- Route
- Subcutaneous injection
- Amount
- Planned 5 mg for participants weighing at least 50 kg; planned 2.5 mg for those under 50 kg
- Frequency
- Once weekly
- Duration
- Primary endpoint at week 24; colon-in-continuity outcomes also assessed at week 48
The sponsor reported lower dose delivery than planned because of preparation and administration. Planned and delivered amounts should not be treated as interchangeable.
Earlier phase 2 crossover study
- Context
- Eight adults with short bowel syndrome and intestinal failure
- Route
- Subcutaneous injection
- Amount
- 5 mg weekly in the placebo-controlled crossover; 10 mg weekly in a later period
- Frequency
- Once weekly
- Duration
- Four weeks per treatment period, with washout between periods
The investigators measured urine output as a marker related to fluid absorption. The 10 mg period followed the controlled crossover.
Research
Research evidence
The strongest controlled result comes from STARS. A nine-person open-label study adds absorption measurements, while an earlier eight-person crossover trial examined fluid-related outcomes.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| STARS phase 3 | 163 adults with short bowel syndrome and intestinal failure | Randomized, double-blind, placebo-controlled trial | Once-weekly subcutaneous trial product | Average weekly support volume decreased 25.5% with apraglutide and 12.5% with placebo at week 24. At least one additional day off support was reported for 43.0% and 27.5%, respectively. | The colon-in-continuity subgroup's week 48 comparisons for days off support and complete independence were not statistically significant. Actual dose delivery was lower than planned. | Controlled human phase 3 evidence |
| Colon-in-continuity metabolic balance study | Nine adults with short bowel syndrome and intestinal failure | Open-label phase 2 study over 52 weeks | Once-weekly subcutaneous trial product | The study reported reduced support volume from baseline and measured increased fluid and energy absorption. | Nine participants and no placebo group limit causal interpretation. | Small uncontrolled human study |
| Fluid-absorption crossover study | Eight adults with short bowel syndrome and intestinal failure | Placebo-controlled crossover followed by another treatment period | 5 mg and 10 mg subcutaneous treatment periods | Urine output increased during active treatment compared with placebo. | The study was small and measured a short-term physiological outcome. | Small controlled human study |
Cautions
Safety and unknowns
- In STARS, serious adverse events occurred in 39 of 110 participants receiving apraglutide and 17 of 53 receiving placebo. These are events during the study, not necessarily effects caused by treatment. The trial was not large enough to resolve rare or long-term risks.
- In the separate, uncontrolled metabolic balance study, serious adverse events were reported in 3 of 9 participants. The investigators assessed one serious event, severe obstructive cholangitis with septic shock, as treatment-related. That participant had pre-existing gallstones.
- In the earlier eight-person study, reported treatment-related events included increased urine output, changes in stoma output, stoma complications, and swelling.
- A reduction in intravenous fluids or nutrition requires careful clinical assessment. The trial followed a defined support-adjustment protocol.
- Rare and long-term effects remain uncertain, and study-product findings do not establish the quality of a different formulation.
Mechanism
How it is proposed to work
Apraglutide activates the GLP-2 receptor, a pathway involved in intestinal adaptation and absorption.
Improved absorption may allow parenteral support to be reduced in a supervised setting. Urine output was one indirect fluid-related measure in an early study.
A plausible mechanism does not determine whether a person will gain days off support or achieve complete independence.
Details
Technical details
Sources
References
- 1.
PubMed. STARS phase 3 trial of apraglutide in short bowel syndrome with intestinal failure
doi:10.1016/j.cgh.2026.08.026 PMID:42692160 NCT04627025
Randomized, placebo-controlled study of parenteral support requirements.
- 2.
PubMed. Apraglutide in short bowel syndrome with colon in continuity: metabolic balance study
doi:10.1016/j.clnu.2024.10.011 PMID:39461299 NCT04964986
Open-label study of nine adults; no placebo group.
- 3.
ClinicalTrials.gov. STARS phase 3 trial registry
NCT04627025
Study design and protocol-specified treatment arms.
- 4.
Other. Apraglutide clinical and regulatory development update
Sponsor reports lower than planned dose delivery in STARS and the need for a confirmatory trial.
- 5.
ClinicalTrials.gov. STARS-2 confirmatory trial registry
NCT07742735
Registered phase 3 study; recruitment and status can change.
- 6.
PubMed. Apraglutide and fluid absorption in a phase 2 crossover study
doi:10.1002/jpen.2223 PMID:34287970 NCT03415594
Eight patients received 5 mg and placebo in a crossover, followed by a 10 mg treatment period.
- 7.
Other. STARS phase 3 safety summary
Sponsor summary of adverse events during the phase 3 trial.
- 8.
Other. STARS investigator abstract describing weight-based doses
doi:10.14309/01.ajg.0001038220.48440.8c NCT04627025
Investigator conference abstract describing the phase 3 weight-based study doses.
- 9.
Other. STARS phase 3 serious adverse event counts
NCT04627025
Sponsor presentation reporting adverse event counts in the phase 3 safety groups.
- 10.
ClinicalTrials.gov. STARS Nutrition metabolic balance study registry and safety results
NCT04964986
Registration and posted safety results for the nine-person open-label study.
- 11.
Other. STARS phase 3 results in the EU Clinical Trials Register
NCT04627025
Final trial results include serious adverse event counts for both study groups.
- 12.
Other. STARS Nutrition metabolic balance study full text
doi:10.1016/j.clnu.2024.10.011 PMID:39461299 NCT04964986
Published study reports the serious biliary event and its assessment.