How GPs can support GI tolerability for patients taking anti-obesity medications

Given that these medications work in part within the digestive system, it’s not surprising that the most common side effects associated with AOMs are GI in nature.^3,4 However, the pathogenesis of GI side effects associated with GLP-1 receptor agonists is not fully understood and appears to be multifactorial.⁵ Associated factors include delayed gastric emptying, altered intestinal motility, and direct effects on the central nervous system.^5,6

Luckily, these side effects tend to be dose-dependent, mostly occurring during initiation and dose escalation, and are typically mild to moderate in nature.³ The four most common GI side effects are nausea, vomiting, diarrhoea, and constipation, although different agents exhibit varying risk profiles:⁷

*Side effects reported in at least 1% of patients on active treatment and more frequently than in patients on placebo from phase 2/3 clinical trials.^8-10

Most of these GI side effects will resolve over time.³ However, because poor tolerability may cause patients to consider discontinuing treatment, supporting those who experience GI side effects through those first few weeks is crucial.^3,5

Nausea and diarrhoea are most likely to occur within the first four weeks of treatment.³ Diarrhoea symptoms may last for a couple of days, while nausea and vomiting will typically resolve within eight days of onset.³

In addition to the general dietary modifications noted above, more specific dietary changes can also help minimise side effects. For nausea, recommend eating crackers, apples, mint, and ginger-based drinks 30 minutes after administering treatment. For diarrhoea, encourage patients to consume chicken broth, rice, carrots, and fruits, while avoiding dairy products, coffee, alcohol, and soft drinks.³

Maintaining hydration is particularly important when vomiting and diarrhoea are present, as dehydration can lead to complications including dizziness, confusion, and fatigue.⁵ For rapid rehydration, consider using an oral rehydration solution (ORS) such as Hydralyte, as they are formulated with the correct balance of glucose and electrolytes to rehydrate faster than water alone.^11-13 By activating sodium-glucose co-transporters in the intestinal lumen, these hypotonic solutions create an osmotic gradient that facilitates fast and effective rehydration.^12,13 In contrast, other electrolyte or sports drinks are typically isotonic, which move water into the body slower than an ORS, so patients should be discouraged from using sports drinks for dehydration.^12,13

If dietary changes and hydration alone are inadequate, pharmacological support can be considered.³ Antiemetic or prokinetic medications can be prescribed for nausea and vomiting, with domperidone recommended over metoclopramide to minimise the risk of extrapyramidal side effects.³ For persistent diarrhoea, probiotic and/or anti-diarrhoeal supplements such as loperamide may be trialled.³

Among the GI side effects described, constipation typically persists longer than the others.³ Patients tend to reduce their water intake secondary to feelings of gastric fullness, which may also contribute to constipation.³ To manage symptoms, ensure patients are consuming an adequate amount of fibre and are keeping well hydrated – an ORS may also be helpful for this.³ Encourage patients to increase their physical activity and, if necessary, recommend a stool softener to help with bowel movements.³

Given that both obesity and constipation are risk factors for anorectal conditions such as haemorrhoids and anal fissures ,¹⁴ discussions about GI side effects also present a good opportunity to ask patients about their bowel habits. Screening for these common issues helps to facilitate early detection and management – especially as patients may feel embarrassed to bring it up themselves. These conditions will also benefit from increased hydration and fibre intake, as well as simple OTC topical treatments, such as glyceryl trinitrate ointment (Rectogesic) for anal fissures.¹⁵

By implementing these management strategies, doctors can support their patients to achieve sustainable use of their AOM, where they are successfully losing weight, tolerating therapy, and experiencing meaningful improvements in overall health and quality of life.