Glucagon-like peptide-1 delays gastric emptying through vagally mediated effects on fundic tone, antral contraction and pyloric resistance, and this contributes to its effect on glucose after meals (Drucker, 2018). The delay is subject to tachyphylaxis: with continuous exposure it weakens within hours to days (Nauck et al., 2011). Long-acting agonists therefore slow the stomach less at steady state than at the start of treatment, although a measurable delay can persist. In a trial of liraglutide in obesity, emptying of solids was clearly slowed after several weeks and less so after several months (Halawi et al., 2017). The practical consequence is that a delayed emptying test in someone still exposed to the drug shows an expected drug effect and says nothing about underlying gastric function.

Gastroparesis is defined by upper gastrointestinal symptoms together with objectively delayed gastric emptying in the absence of mechanical obstruction (Camilleri et al., 2022). The reference test is scintigraphy of a standard low-fat, egg-white meal with imaging to four hours, and retention of more than ten per cent of the meal at four hours is the accepted criterion for delay (Tougas et al., 2000; Abell et al., 2008). Shorter protocols and non-standard meals misclassify patients in both directions. Symptom severity is commonly recorded with the Gastroparesis Cardinal Symptom Index (Revicki et al., 2003). European consensus adds that symptoms correlate only loosely with the degree of delay (Schol et al., 2021).

Women make up the great majority of patients with idiopathic gastroparesis in registry data (Parkman et al., 2011), and healthy women empty solids more slowly than men (Datz et al., 1987). Functional dyspepsia, defined by the Rome IV criteria (Stanghellini et al., 2016), produces the same symptoms, is also more frequent in women, and overlaps with gastroparesis to the point that the two have been described as interchangeable syndromes in tertiary care (Pasricha et al., 2021). A woman in midlife who starts weight loss therapy may thus have had mild, unrecognised symptoms beforehand. Rapid weight loss adds its own hazards, among them gallstone disease. Any pathway has to separate a drug effect from a coincident or unmasked disorder.

The clinician draws up a dated record of the drug, its dose escalations, missed and final doses, and the onset and course of each symptom, set beside body weight. Symptoms that appeared at a dose increase and eased between increases suggest a pharmacological effect. Symptoms present before the first injection suggest a pre-existing disorder. The history should also establish whether the patient has diabetes, since long-standing diabetes is itself a cause of gastroparesis, and should record previous gastric or bariatric surgery, thyroid disease, and the use of opioids, anticholinergic drugs and cannabis.

Guidelines require mechanical obstruction to be excluded before gastroparesis is diagnosed (Camilleri et al., 2022). Upper endoscopy is the usual means, with cross-sectional imaging when small bowel obstruction is possible. In this setting the differential diagnosis is wider than usual. Gallstones and pancreatitis should be considered in anyone with pain after rapid weight loss, and pancreatitis and bowel obstruction were among the events associated with these drugs in the analysis by Sodhi et al. (2023). Rumination syndrome, cyclic vomiting and cannabinoid hyperemesis can each be mistaken for gastroparesis, and each is managed differently. Marked weight loss can, rarely, lead to compression of the duodenum by the superior mesenteric artery.

If the drug has not already been stopped, it is stopped in agreement with the prescriber. The length of observation must respect pharmacokinetics. Semaglutide has an elimination half-life of about one week, so meaningful concentrations remain for more than a month after the last dose, and the picture for other weekly agents is similar. Symptoms are scored at regular intervals with a validated instrument through this period. Improvement that follows the expected clearance of the drug supports a drug effect. Persistence well beyond it is the finding that makes the label refractory worth using, and it is the point at which formal testing becomes informative.

Scintigraphy is performed according to the consensus protocol, with the standard meal, imaging to four hours and prior withdrawal of other drugs that alter motility (Abell et al., 2008). In patients with diabetes the blood glucose is checked beforehand, because marked hyperglycaemia slows emptying. A test done while the incretin drug is still active should be labelled as such and not used to diagnose gastroparesis. Where scintigraphy is unavailable, a validated breath test is an accepted alternative (Camilleri et al., 2022).

Three outcomes are possible. Delayed emptying with compatible symptoms after washout meets the definition of gastroparesis. Normal emptying with persistent symptoms points to functional dyspepsia or another disorder identified at Step 2. Resolution of symptoms before testing indicates a reversible drug effect. For the first two, the probability that the drug was responsible is graded with a structured instrument such as the adverse drug reaction probability scale of Naranjo et al. (1981), which weighs timing, response to withdrawal, alternative causes and rechallenge. The grade is recorded in words. In most cases it will be no stronger than possible or probable, and the notes should say so.

Management follows existing guidance for gastroparesis and does not differ because of the suspected cause (Camilleri et al., 2022; Schol et al., 2021). It begins with dietary change towards small, low-fat, low-residue meals and with attention to hydration and micronutrients, which matter particularly after substantial weight loss. Antiemetic and prokinetic drugs are added according to licensed indications and local practice. For patients who remain symptomatic, the expert review by Lacy et al. (2022) describes the options, including neuromodulators, pyloric intervention in carefully selected patients with confirmed delay, and enteral feeding when oral intake fails. This article proposes no new treatment and no dosing.

The final step is a shared decision about obesity treatment, since the condition that prompted therapy remains. Options include no further incretin-based drug, a cautious retrial, or a different approach altogether. Rechallenge gives the strongest evidence on causality but exposes the patient to recurrence, and it should be considered only when symptoms resolved fully and the patient wishes it. A suspected serious reaction is reported to the national pharmacovigilance scheme whatever the causality grade.