IBS-C Treatment Gap: Why Few Patients Use Prescription Options

Only a Fraction of IBS-C Patients Use Prescription Treatments — New Research Explains Why Better Options Are Coming

Two recent studies point to the same problem in irritable bowel syndrome with constipation (IBS-C): current treatments help only a subset of patients, and side effects drive many to quit. A 2022 review from researchers at Washington University School of Medicine and the University of Louisville, published in Expert Opinion on Emerging Drugs, found that only a small percentage of IBS patients take prescription therapies at all. Meanwhile, a Swedish cross-analysis of the GLP-1 receptor agonist ROSE-010 suggests that matching drugs to the right patient subgroups — especially IBS-C — could change that picture.

Why IBS-C Is Hard to Treat: One Disorder, Many Mechanisms

IBS is defined by symptoms — chronic abdominal pain plus altered bowel habits — rather than by a single measurable cause. As Elwing and colleagues at Washington University and the University of Louisville explain, the pathogenesis is multifactorial: gut motility problems, visceral hypersensitivity, altered intestinal secretion, microbiome disturbances, and gut-brain signaling dysfunction can all contribute in different patients. Their review, published in Expert Opinion on Emerging Drugs in March 2022, draws a direct conclusion from this: any given therapy will only prove effective in a subset of sufferers.

That conclusion matches real-world behavior. Limited symptom responses and side effect experiences lead to considerable patient dissatisfaction, and the review notes that a large gap exists between the number of people diagnosed with IBS-C and those actually filling prescriptions. As we’ve covered in our analysis of why patients stop IBS-C medications, this dissatisfaction is well documented outside clinical trials too.

ROSE-010: A GLP-1 Receptor Agonist That Works Best for IBS-C

One of the more interesting candidates comes from an unexpected direction. ROSE-010, a glucagon-like peptide-1 (GLP-1) receptor agonist delivered by subcutaneous injection, was originally developed with metabolic disease in mind. GLP-1 receptors sit in the gut and nervous system, and stimulating them slows gastric emptying and modulates visceral pain signaling — relevant mechanisms in IBS.

In the 2022 cross-analysis published in the Scandinavian Journal of Gastroenterology, Touny and colleagues at Uppsala University re-analyzed data from 166 participants (116 females, 50 males) who received ROSE-010 at 100 µg or 300 µg versus placebo. The results were dose- and time-dependent: maximum pain relief occurred at 300 µg, 120 minutes after injection. Pain relief was greatest in constipation-dominant IBS and mixed IBS, relative to diarrhea-dominant and unspecified subtypes. Women showed greater pain relief than men, while age and BMI had no effect on response.

Notably, ROSE-010 is designed for acute pain relief during IBS attacks, not daily maintenance. That limitation matters — it addresses pain but not the underlying bowel habit disturbance, and it requires self-injection, which some patients may find unacceptable.

The Emerging Drug Pipeline: Serotonin, Cannabinoids, and Bile Acids

The Washington University-led review maps out where IBS-C drug development is heading beyond GLP-1:

• Serotonergic targets. Roughly 95% of the body’s serotonin is produced in the gut, where 5-HT4 receptor activation drives intestinal secretion and motility. Serotonin receptor drugs remain a major focus for constipation-predominant subtypes.
• Endogenous opioid receptors. Peripheral opioid agonists that act on gut motility without crossing into the central nervous system are being refined to avoid the nausea and psychiatric side effects that led to earlier drug withdrawals.
• The endocannabinoid system. Compounds targeting CB1 and related receptors may modulate visceral pain and intestinal secretomotor function, offering a mechanistically distinct approach.
• Bile acid signaling. Because bile acids reaching the colon increase water secretion and motility, manipulating bile acid secretion and sequestration is an active strategy for both IBS-C and IBS-D.

Some of these pathways connect to broader gut ecology and microbiome research, since bile acids and serotonin are both shaped by bacterial metabolism in the intestine. The mechanisms overlap with current FDA-approved options like linaclotide, which we compare directly in our piece on linaclotide versus tenapanor for IBS-C.

What This Means for Patients Now

Practically, these findings argue for patience and precision. If you have IBS-C with prominent pain episodes, acute-acting agents like ROSE-010 — if approved — may eventually offer on-demand relief, and female patients appear more likely to respond. But the research also confirms something patients already know from experience: trial and error is built into IBS-C treatment, because the disorder’s biology varies from person to person.

Work with a gastroenterologist willing to sequence treatments based on your dominant symptom — pain versus constipation versus bloating — rather than treating IBS-C as a single condition. Documenting response to each therapy matters, since even a 30–50% improvement in symptoms is what most trials define as a clinically meaningful responder.

Frequently Asked Questions

What is ROSE-010 and how is it different from existing IBS-C medications?

ROSE-010 is an injectable GLP-1 receptor agonist intended for acute relief of IBS pain attacks rather than daily maintenance, whereas drugs like linaclotide and lubiprostone are taken regularly to treat constipation and pain over time.

Did ROSE-010 work better in certain patients?

Yes. In the cross-analysis of 166 participants, pain relief was greatest in IBS-C and IBS-M patients at the 300 µg dose, and women responded better than men.

Why do so few IBS-C patients use prescription drugs?

According to the 2022 review, limited symptom improvement and side effects cause considerable dissatisfaction, so many patients never start or continue prescription therapy.

Which new treatment targets are being studied for IBS-C?

Current research focuses on serotonin receptors, peripheral opioid receptors, the endocannabinoid system, bile acid modulation, and visceral sensory signaling pathways.

Conclusion

IBS-C treatment is moving away from one-size-fits-all prescribing. The 2022 review from Elwing and colleagues frames IBS’s mechanistic diversity as an opportunity for genuinely new drugs, while the Uppsala ROSE-010 analysis shows how identifying the right subpopulation — constipation-predominant patients, and especially women — can turn a modest drug into a meaningful one. For now, informed trial-and-error remains the standard; targeted therapies are the direction of travel.

Sources:
https://pubmed.ncbi.nlm.nih.gov/35266839/
https://pubmed.ncbi.nlm.nih.gov/35234561/
https://pubmed.ncbi.nlm.nih.gov/35123085/
https://pubmed.ncbi.nlm.nih.gov/34727333/
https://pubmed.ncbi.nlm.nih.gov/34463082/