Which drugs flag for gastric motility risks

A study published in PLoS ONE on 12 June 2026 by Zhiheng Qian and Ni Jiang used disproportionality analysis across two large pharmacovigilance databases, the FDA Adverse Event Reporting System (FAERS) and Canada's CVARD, to identify which drugs carry the strongest statistical signals for gastric motility disorders^[1]. The analysis covered more than 58 million FAERS reports filed between 2004 and 2025.

Of the drugs screened, semaglutide showed the strongest association with impaired gastric emptying, with a reporting odds ratio (ROR) of 80.27 (95% CI: 76.39 to 84.34). That signal was validated in the CVARD database at an ROR of 54.17^[1]. In total, 20 drugs produced positive signals across all three statistical methods the authors used.

What the study measured

The researchers searched FAERS for seven MedDRA preferred terms related to gastric motility: gastro-oesophageal reflux disease, duodenogastric reflux, gastric atony, impaired gastric emptying, gastric hypomotility, gastro-oesophageal sphincter insufficiency, and regurgitation. They applied three disproportionality algorithms (ROR, PRR, and BCPNN) and required all three to flag a drug before calling the signal positive^[1].

They then validated the signals in the CVARD (Canada Vigilance Adverse Reaction Online Database) where possible. Of the 20 drugs flagged, three were absent from CVARD entirely.

GLP-1 agonists dominated the results

Four GLP-1 receptor agonists appeared in the top 20: semaglutide (ROR 80.27), dulaglutide (ROR 37.28), liraglutide (ROR 10.82), and exenatide (ROR 10.06 for gastric hypomotility). Semaglutide's signal was the largest of any drug in the entire analysis^[1]. This is consistent with the known mechanism of GLP-1 receptor agonists, which slow gastric emptying as part of their pharmacological action.

The gap between semaglutide and the next GLP-1 agonist (dulaglutide) is worth noting. Semaglutide's ROR of 80.27 is roughly double dulaglutide's 37.28. That may partly reflect prescribing volume: semaglutide has become the most widely prescribed GLP-1 agonist globally, and the Weber effect (newer, higher-profile drugs attract disproportionately more adverse event reports) is a recognised phenomenon in pharmacovigilance. The authors validated semaglutide's signal in the CVARD database (ROR 54.17), which adds confidence that the signal is real even if the magnitude is uncertain^[1].

A separate 2023 study by Sodhi et al. in JAMA, using insurance claims data rather than pharmacovigilance reports, also found elevated risks of gastrointestinal adverse events (including gastroparesis) in patients taking GLP-1 agonists for weight loss^[2]. The Qian and Jiang analysis adds a different evidence layer by using spontaneous reporting databases and covering a broader drug set.

Other drug classes flagged

Beyond GLP-1 agonists, the analysis identified signals for insulin degludec (ROR 18.90), the angiotensin receptor blocker olmesartan (ROR 28.40 for GERD), the proton pump inhibitor esomeprazole (ROR 43.17 for sphincter insufficiency), trofinetide (ROR 28.93 for regurgitation), bisphosphonates (alendronate, pamidronate), and several others including metformin, sitagliptin, and cyclosporine^[1].

The Weibull time-to-onset analysis showed that timing varies widely. Trofinetide-related events had a median onset of 6.6 days, while immunoglobulin G-related events had a median onset of 535.1 days. The GLP-1 agonists fell between these extremes.

What this does and does not tell us

Disproportionality analysis measures whether a drug-event pair is reported more often than expected, relative to all other drugs in the database. It does not estimate incidence, because there is no denominator (the total number of patients exposed is unknown). It cannot prove causation. Spontaneous reporting systems also carry well-known biases: underreporting, selective reporting, and the Weber effect (newer drugs attract more reports)^[1].

The authors note that 67.99% of reports lacked time-to-onset data, which limits the generalisability of the Weibull analysis. Confounding by indication is another concern: metoclopramide, for example, is prescribed to treat gastroparesis, so reports of gastric motility disorders in metoclopramide users may reflect the underlying condition rather than a drug effect.

For GLP-1 agonists specifically, the high ROR values are notable but should be read alongside the fact that delayed gastric emptying is a known, expected pharmacological effect of the drug class, not an unexpected safety signal. The prescribing information for semaglutide already lists gastrointestinal adverse events prominently. Nausea, vomiting, diarrhoea, and constipation are among the most commonly reported side effects in randomised trials of the drug. The disproportionality signal confirms that these reports also appear at elevated rates in post-market surveillance.

It is also worth noting that tirzepatide, the dual GIP/GLP-1 receptor agonist, was not among the 20 drugs flagged in this analysis. Whether that reflects lower reporting volume, a different gastrointestinal profile, or the time period covered by FAERS is not addressed in the paper.

Why this matters for patients and clinicians

The practical value of this kind of analysis is in flagging drug classes that may need closer gastrointestinal monitoring, particularly in patients on polypharmacy regimens. A patient taking a GLP-1 agonist alongside a bisphosphonate or an angiotensin receptor blocker, all of which appeared in this analysis, could face compounding effects on gastric motility. That possibility deserves clinical attention even if no single drug is proven to cause gastroparesis by this method alone.

Clinicians managing patients on multiple medications with known gastric motility effects should be aware of the cumulative risk. For patients, the key takeaway is that gastrointestinal symptoms while on a GLP-1 agonist are well-documented in both trial data and pharmacovigilance databases, and reporting such symptoms to a prescriber is appropriate.

This article is for informational purposes only and does not constitute medical advice. If you are experiencing gastrointestinal symptoms while taking any medication, consult a qualified healthcare provider.