Four Months of Stomach Pain on Semaglutide, and the Biopsy Found Immune Cells Where They Should Not Be

Nausea and stomach upset are so routine on GLP-1 drugs that most patients and prescribers treat them as background noise. That expectation is exactly what made one Saudi case worth publishing.

A 57-year-old woman with type 2 diabetes had been on semaglutide when she developed epigastric pain, loss of appetite, and unintended weight loss that dragged on for four months. Her bloodwork showed marked peripheral eosinophilia, and endoscopic biopsies of her stomach and duodenum revealed extensive eosinophilic infiltration of the lamina propria, confirming eosinophilic gastroenteritis.

The case was published in the August 2026 issue of the International Journal of Research in Medical Sciences by a team from Security Forces Hospital in Makkah, led by Abrar A. Oraijah with gastroenterologist Mansour Alghamdi.

Four Months of Pain and an Eosinophil Count That Would Not Settle

Eosinophilic gastroenteritis is uncommon on its own. It occurs when eosinophils, white blood cells normally deployed against parasites and in allergic reactions, accumulate in the wall of the digestive tract and drive inflammation in that tissue. Symptoms are frustratingly nonspecific: abdominal pain, nausea, poor appetite, sometimes obstruction.

Before attributing anything to the drug, the treating team worked through the usual suspects. Parasitic infection, allergic disease, and blood cancers were investigated and excluded. What remained was the timing, and the timing was tight enough that clinicians stopped the semaglutide.

That exclusion work matters. Eosinophilia has a broad differential, and parasites, in particular, are the most common explanation worldwide. Ruling those out is what converts a coincidence into something a journal will print.

The One Piece of Evidence That Lifts This Above Coincidence

Anyone can find a temporal association between a widely prescribed drug and a rare condition. KFF polling now puts about one in eight American adults on a GLP-1 drug at any given moment, so overlap with uncommon diseases is guaranteed by arithmetic alone.

What distinguishes this report is what happened after withdrawal. Over the following months, the patient’s symptoms resolved and her eosinophil count returned to normal. Then the team repeated the endoscopic biopsies, and the tissue showed histological resolution.

That sequence, known as a dechallenge, is one of the stronger signals available from a single case because the abnormality reversed at the tissue level rather than just in the patient’s description of how she felt. It still falls well short of proof. Nobody rechallenged the patient by restarting the drug, which would have been unethical, and a single case cannot rule out that the illness ran its own course.

The publication venue is worth flagging too. This is an open-access journal without the editorial reach of a major gastroenterology title, which is common for case reports but means less specialist scrutiny.

Registry Data Point the Same Direction

The strongest evidence here is not a case report at all. Researchers at the University of Southern Denmark ran a nationwide sequence symmetry analysis using Danish health registries, identifying everyone who started a GLP-1 drug, an SGLT2 inhibitor, or a DPP-4 inhibitor between 2015 and 2024 and who recorded an eosinophil count at or above 1.5 billion per liter in the 180 days before or after.

Their finding was that hypereosinophilia was about three times more likely after starting a GLP-1 drug than before, a pattern that held across shorter and longer observation windows and for semaglutide specifically. The comparator drug classes showed no such signal.

A sequence symmetry design is self-controlled, which removes much confounding, but it measures a laboratory abnormality rather than a diagnosed illness.

A Handful of Reports Across Several Organs

The Makkah case is not free-standing. Over roughly three years, similar reports have accumulated across several countries, each describing eosinophils appearing where they should not be.

Rheumatologists in Cali, Colombia, described a 42-year-old woman who developed eosinophilic fasciitis after starting weekly semaglutide, severe enough that they stopped the drug and treated her with pulses of methylprednisolone and intravenous cyclophosphamide. In Monterrey, Mexico, a 46-year-old man six months into semaglutide developed progressive difficulty swallowing and turned out to have eosinophilic esophagitis with food impacted 40 centimeters down. Belgian clinicians reported eosinophilic duodenitis presenting as a bowel obstruction, and a conference abstract described what its authors called the first case of semaglutide-associated eosinophilic colitis.

Fascia, esophagus, duodenum, stomach, colon. The pattern is consistent in mechanism even where it varies in location, and the proposed explanation is a drug-induced hypersensitivity reaction rather than the motility slowdown behind ordinary GLP-1 nausea.

Set against the scale of prescribing, these numbers remain vanishingly small. A disproportionality analysis of the FDA’s adverse event database found 21,281 reports of gastrointestinal toxicity among 81,752 adverse event reports for this drug class, with semaglutide carrying the strongest signal. Eosinophilic disease is not among the commonly reported problems. Nausea, vomiting, diarrhea, and constipation still dominate.

What Patients on These Drugs Should Actually Take from This

The clinically useful line in the Makkah report is aimed at doctors. Its authors argue for a higher index of suspicion when someone on a GLP-1 drug presents with persistent or atypical gastrointestinal symptoms, because catching a drug-induced eosinophilic disorder early and stopping the drug can lead to complete recovery.

The practical distinction is duration and character. Nausea in the first weeks after starting or increasing a dose, easing over time, matches the expected profile. Pain that persists for months, appetite loss, weight loss beyond what the drug would explain, or trouble swallowing are different signals and worth reporting to a prescriber.

Nobody should stop a prescribed medication based on a case report. These drugs carry documented benefits for blood sugar, weight, and cardiovascular risk, and the eosinophilic complications described so far are rare and appear reversible on withdrawal. But a blood count is inexpensive, and an unexplained high eosinophil count deserves a next question rather than a shrug.

Key Questions Answered

What happened in this case?

A 57-year-old woman with type 2 diabetes on semaglutide developed four months of epigastric pain, appetite loss, and weight loss. Blood tests showed marked eosinophilia, and stomach and duodenal biopsies confirmed eosinophilic gastroenteritis.

Does this prove semaglutide caused it?

No. A single case report cannot establish causation. The strongest evidence here is that symptoms, blood counts, and biopsy findings all normalized after the drug was stopped, which is suggestive but not conclusive.

Is there anything beyond case reports?

Yes. A nationwide Danish registry analysis found hypereosinophilia roughly three times more likely after starting a GLP-1 drug than before, a signal not seen with two comparator diabetes drug classes.

How common is this?

Rare. Only a handful of eosinophilic disease cases have been published worldwide against enormous prescribing volumes. Nausea, vomiting, diarrhea, and constipation remain the dominant gastrointestinal side effects.

Which symptoms are worth reporting to a doctor?

Pain lasting months rather than weeks, appetite loss, unexplained weight loss beyond what the drug would account for, or new difficulty swallowing. Early nausea that fades matches the expected drug profile.

Should anyone stop their GLP-1 medication over this?

No. Decisions about prescribed medication should be made by a clinician who knows the individual case, and stopping abruptly carries its own risks.