Sulphur burps and diarrhoea are among the most commonly reported gastrointestinal side effects associated with retatrutide, an investigational triple receptor agonist currently in clinical trials. By activating GLP-1, GIP, and glucagon receptors simultaneously, retatrutide slows gastric emptying and alters gut motility — processes that can trigger foul-smelling burps and loose stools, particularly during dose escalation. This article explains why these symptoms occur, how frequently they are reported in trial data, and what practical dietary, lifestyle, and medical strategies may help manage them safely.

Why Retatrutide Can Cause Sulphur Burps and Diarrhoea

Retatrutide slows gastric emptying via GLP-1 receptor activation, promoting bacterial fermentation of sulphur-containing foods and producing hydrogen sulphide gas; diarrhoea arises from altered gut motility, bile acid metabolism, and microbiota changes.

Retatrutide is an investigational triple agonist that simultaneously activates glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors.^[4][5] This multi-receptor activity distinguishes it from earlier agents such as semaglutide or tirzepatide, and is central to understanding why gastrointestinal side effects — including sulphur burps and diarrhoea — may occur.

GLP-1 receptor activation slows gastric emptying (delayed gastric emptying).^[1][2] When food remains in the stomach and upper intestine for longer than usual, it may undergo additional fermentation by gut bacteria. This bacterial breakdown of sulphur-containing proteins — found in foods such as eggs, meat, and cruciferous vegetables — is thought to produce hydrogen sulphide gas, which may be expelled as burps with a characteristic rotten-egg odour. It is important to note that this mechanism is a plausible hypothesis based on what is understood about GLP-1-based therapies more broadly; direct evidence specific to retatrutide remains limited. Other causes of foul-smelling burps — such as small intestinal bacterial overgrowth (SIBO), Helicobacter pylori infection, or giardiasis — should be considered if symptoms are persistent or accompanied by fever, significant weight loss, or prolonged diarrhoea.

Diarrhoea is thought to arise through a combination of mechanisms, though these remain incompletely understood. Changes in gut motility, altered bile acid metabolism, and shifts in gut microbiota composition may all contribute. These effects are generally dose-dependent, tending to be more pronounced during dose-escalation phases of treatment. The contribution of glucagon receptor activation to intestinal fluid secretion has been proposed but is not yet established, and should be regarded as speculative at this stage.

Retatrutide has not yet received marketing authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) or the European Medicines Agency (EMA).^[7] All current understanding of its side-effect profile is derived from phase 2 and ongoing phase 3 clinical trial data, and the full safety profile continues to be evaluated.

How Common Are These Gastrointestinal Side Effects?

Diarrhoea was reported in approximately 20–30% of participants at higher doses in the phase 2 trial; sulphur burps are not captured as a discrete adverse event but are a recognised patient complaint across the GLP-1 agonist class.

Based on data from the phase 2 clinical trial of retatrutide (NCT04881760), published in the New England Journal of Medicine in 2023, gastrointestinal adverse events were among the most frequently reported side effects across all dose groups.^[4][10] Nausea, vomiting, diarrhoea, and constipation were collectively experienced by a substantial proportion of participants, with higher doses associated with greater incidence and severity.

In that trial, diarrhoea was reported in approximately 20–30% of participants receiving higher doses of retatrutide, with rates varying by dose level and stage of titration.^[4][10] These figures are drawn from the published phase 2 data and should be interpreted in the context of a controlled trial population; rates in broader clinical use may differ. Sulphur-smelling burps are not captured as a discrete adverse event in clinical trial reporting — they are typically subsumed under broader categories such as 'eructation' (belching). Patient-reported experiences across the GLP-1 receptor agonist class suggest they are a recognisable complaint, though direct evidence specific to retatrutide is currently anecdotal.

Gastrointestinal side effects were most prevalent during the dose-escalation period — the weeks during which the dose is gradually increased towards the target maintenance level. For many participants, symptoms improved or resolved once a stable dose was reached. A minority of trial participants discontinued treatment due to gastrointestinal events, underscoring the importance of appropriate dose titration and proactive symptom management.

Individual responses vary considerably. Factors such as baseline gut motility, dietary habits, concurrent medications, and metabolic health may all influence how prominently these symptoms present. Experiencing these effects does not necessarily mean that treatment is unsuitable.

Managing Digestive Symptoms During Retatrutide Treatment

Smaller meals, reduced sulphur-rich foods, adequate hydration with oral rehydration salts, and clinician-guided dose titration are the primary strategies for managing retatrutide-related gastrointestinal symptoms.

Effective management of sulphur burps and diarrhoea during retatrutide treatment begins with setting realistic expectations. Patients should be counselled before starting treatment that gastrointestinal symptoms are common, particularly in the early weeks, and that they often diminish over time as the body adjusts to the medication.

Practical strategies for managing symptoms include:

• Eating smaller, more frequent meals rather than large portions, which can overwhelm a stomach that is already emptying more slowly

• Eating slowly and chewing food thoroughly to reduce the volume of air swallowed and ease digestive burden

• Reducing foods high in sulphur during periods of active symptoms — these include eggs, red meat, garlic, onions, and cruciferous vegetables such as broccoli and cabbage. These are optional strategies that may help some people; overall nutritional adequacy should be maintained

• Staying well hydrated, particularly if diarrhoea is present, to prevent dehydration. Oral rehydration salts (such as Dioralyte) are recommended by the NHS for replacing lost fluids and electrolytes^[8][9]

• Avoiding carbonated drinks and alcohol, which can worsen bloating and loose stools

From a pharmacological standpoint, dose titration is the most important management tool. Because retatrutide is investigational, any adjustment to the dose-escalation schedule must be directed by the prescribing clinician or trial team — patients should not alter their dosing independently.

For mild, non-bloody diarrhoea without fever, short-course loperamide may be considered following pharmacist or clinician advice, in line with NHS self-care guidance. Simeticone-containing products may offer some relief from bloating and gas. However, patients should consult their prescribing clinician, trial team, or pharmacist before adding any new medication, as interactions and contraindications must be considered on an individual basis.

If symptoms are persistent or significantly restrict dietary intake, referral to a registered dietitian should be considered to ensure nutritional needs continue to be met.

When to Seek Medical Advice About Your Symptoms

Seek prompt medical attention for bloody or persistent diarrhoea, signs of dehydration, severe abdominal pain, or symptoms suggesting pancreatitis or gallbladder disease; call 999 for severe or rapidly worsening symptoms.

Whilst mild gastrointestinal symptoms are expected and generally self-limiting during retatrutide treatment, certain presentations warrant prompt medical attention. Patients should be clearly informed of the signs that distinguish manageable side effects from potentially serious complications.

Contact your GP, trial team, or call NHS 111 promptly if you experience:

• Diarrhoea that is severe, bloody, or persists for more than 48–72 hours without improvement

• Signs of dehydration, including dizziness, reduced urine output, dry mouth, or confusion

• Significant abdominal pain, particularly if severe or radiating to the back — this may rarely indicate pancreatitis, a recognised risk associated with GLP-1-based therapies

• Pain in the upper right abdomen, fever, or yellowing of the skin or eyes (jaundice) — these may suggest gallbladder disease, another recognised complication of this drug class^[23][24]

• Severe constipation, abdominal distension, or inability to pass wind or stools — these may rarely indicate intestinal obstruction or ileus, for which the MHRA and EMA have issued safety communications in relation to GLP-1 receptor agonists^[11][12]

• Unexplained weight loss beyond what is expected from the treatment

• Vomiting that prevents adequate fluid or food intake

Call 999 or go to your nearest A&E immediately if symptoms are severe, rapidly worsening, or you are unable to keep any fluids down.

Pancreatitis and gallbladder disease, though uncommon, are recognised risks associated with GLP-1 receptor agonist use, as documented in the Summary of Product Characteristics (SmPC) for licensed agents in this class (such as semaglutide). Patients with a personal history of pancreatitis, gallstones, or significantly elevated triglycerides should ensure their prescribing clinician or trial team is aware of these risk factors before commencing treatment.

In the context of a clinical trial, participants should contact their trial site medical team as the first point of contact for any concerning symptoms. Do not stop treatment abruptly without medical guidance, as this may affect glycaemic control or weight management outcomes.

If you believe you have experienced a side effect from retatrutide within a clinical trial, you should report this to your trial team. Suspected adverse drug reactions to any medicine can also be reported directly to the MHRA via the Yellow Card Scheme at yellowcard.mhra.gov.uk or through the Yellow Card app.

Dietary and Lifestyle Changes That May Help

Reducing high-sulphur and high-fat foods, eating smaller regular meals, staying hydrated, and keeping a food and symptom diary are practical dietary strategies that may reduce retatrutide-related digestive discomfort.

Dietary modification can play a meaningful role in reducing the frequency and severity of sulphur burps and diarrhoea associated with retatrutide. Because the drug slows gastric emptying, the digestive system may become more sensitive to the volume and composition of meals. Adapting eating habits accordingly can make a significant difference to day-to-day comfort, though responses vary between individuals and these suggestions should be treated as strategies to try rather than firm rules.

Foods to consider reducing or avoiding during symptomatic periods:

• High-sulphur foods: eggs, red meat, poultry skin, garlic, onions, leeks, and cruciferous vegetables

• High-fat or fried foods, which may further delay gastric emptying

• Highly processed foods and those containing artificial sweeteners, which may worsen loose stools in some people

• Caffeine and alcohol, both of which can irritate the gastrointestinal tract

Foods that may be better tolerated:

• Plain, low-fat carbohydrates such as rice, plain pasta, and toast

• Cooked vegetables rather than raw, which are generally easier to digest

• Lean proteins such as fish or tofu

• Probiotic-containing foods such as live yoghurt, which some people find helpful for gut comfort; evidence in this specific context is limited, so consider trialling for a few weeks and stopping if there is no benefit

The NHS Eatwell Guide provides a useful framework for maintaining a balanced diet when modifying food intake to manage symptoms.^[19][20] Patients are encouraged to avoid overly restrictive eating, which may compromise nutritional adequacy.

Beyond diet, lifestyle factors also matter. Regular, gentle physical activity such as walking can support gut motility and reduce bloating. Eating at regular intervals rather than skipping meals helps maintain a predictable digestive rhythm. Stress management is also relevant, as psychological stress is known to exacerbate gastrointestinal symptoms through the gut-brain axis.^[26][27]

Keeping a simple food and symptom diary during the early weeks of treatment can help identify personal trigger foods and provide useful information to share with the healthcare team. If symptoms persist or dietary intake becomes significantly restricted, ask your GP or trial team for a referral to a registered dietitian.

What Current Evidence and Clinical Trials Tell Us

Phase 2 data showed gastrointestinal events were the most common side effects of retatrutide, mostly mild to moderate; no MHRA or NICE guidance exists yet, as the drug remains investigational pending phase 3 results.

Retatrutide is currently under investigation in a global phase 3 clinical trial programme, following promising results from its phase 2 study (NCT04881760) published in the New England Journal of Medicine in 2023.^[4][10] The phase 2 data demonstrated substantial weight loss — up to 24.2% of body weight at the highest dose over 48 weeks — alongside improvements in glycaemic control, making it one of the most efficacious agents studied to date in this class.

Gastrointestinal adverse events, including diarrhoea, nausea, and vomiting, were consistently the most common side effects reported across all dose groups in the phase 2 trial. The majority of these events were rated as mild to moderate in severity, and most resolved without requiring treatment discontinuation. The structured dose-escalation protocol used in the trial was specifically designed to mitigate gastrointestinal burden, and this approach is likely to inform any future prescribing guidance.

There is currently no official regulatory guidance from the MHRA, NICE, or EMA specifically addressing retatrutide, as the drug has not yet received marketing authorisation in the United Kingdom or European Union.^[7] Clinicians and patients should therefore rely on peer-reviewed trial publications and the oversight of trial ethics committees for safety information at this stage. Details of ongoing phase 3 studies can be found on ClinicalTrials.gov.

The phase 3 programme is expected to provide more robust data on long-term gastrointestinal tolerability, including the durability of symptom resolution and the impact of different titration schedules. As evidence matures, it is anticipated that clinical guidelines will be developed to support safe and effective use of retatrutide, should it receive regulatory approval. Until then, any use outside of a clinical trial setting would be considered off-label and is not currently recommended.

Frequently Asked Questions