Sulfur Burps and Diarrhoea: Retatrutide Trials

Sulfur burps and diarrhoea have been reported among gastrointestinal side effects in retatrutide clinical trial participants. Retatrutide is an investigational triple agonist medicine, acting on GLP-1, GIP and glucagon receptors, currently studied in the TRIUMPH and TRANSCEND trial programmes for obesity and type 2 diabetes. It holds no marketing authorisation in the UK or elsewhere and is not available outside an authorised clinical trial. This article summarises what clinical trial data report about these digestive symptoms, when they may require medical attention, and how trial protocols have approached their management.

What is retatrutide and what is its current status in the UK?

Retatrutide has no UK marketing authorisation and is available only within an authorised clinical trial. It is an investigational GLP-1, GIP and glucagon triple receptor agonist not accessible through NHS prescribing, private clinics or online pharmacies.

Retatrutide holds no marketing authorisation in the UK or anywhere else, and it can be prescribed or supplied only within an authorised clinical trial.^[13][17] It is an investigational medicine being studied for the management of obesity and type 2 diabetes. Unlike authorised incretin-based medicines such as semaglutide (a GLP-1 receptor agonist, licensed for weight management as Wegovy and for type 2 diabetes as Ozempic) or tirzepatide (a dual GIP/GLP-1 receptor agonist, licensed as Mounjaro), retatrutide is not available through NHS prescribing, private clinics or online pharmacies.^[8][9] Any product sold online under this name is not a licensed medicine and may be falsified.

Retatrutide acts on three hormone receptors simultaneously: the glucagon-like peptide-1 (GLP-1) receptor, the glucose-dependent insulinotropic polypeptide (GIP) receptor, and the glucagon receptor.^[6][7] This triple agonist mechanism distinguishes it pharmacologically from currently authorised dual or single agonists, and it is the subject of ongoing investigation in the TRIUMPH and TRANSCEND clinical trial programmes.^[13][17]

Because retatrutide is investigational, no UK regulatory authority has assessed its benefit-risk profile for routine clinical use. The MHRA has not authorised it, and NICE has not evaluated it. No launch date or approval timeline can be given. If you are interested in licensed weight-management treatments, a GP can discuss options that are currently available.

How common are these gut side effects in clinical trial participants?

Gastrointestinal events were the most common treatment-emergent adverse effects in the retatrutide Phase 2 trial, with nausea and diarrhoea reported most frequently during dose escalation. Most events were mild to moderate in intensity.

Gastrointestinal side effects, including eructation (burping), diarrhoea, nausea and vomiting, were among the most frequently reported adverse events in retatrutide clinical trial participants. In the Phase 2 trial published in the New England Journal of Medicine (Jastreboff et al., 2023), gastrointestinal events were the most common treatment-emergent adverse effects across all dose groups studied, with nausea and diarrhoea reported particularly during dose escalation periods.

Sulfur-smelling burps, sometimes described as "eggy" or sulphurous eructation, are not unique to retatrutide. Eructation and diarrhoea are listed as recognised adverse effects of authorised medicines in the GLP-1 receptor agonist class, including in the UK patient information leaflets for semaglutide (Wegovy) and tirzepatide (Mounjaro). The mechanism by which slowed gastric emptying, a pharmacological effect of GLP-1 activity, may allow gut bacteria more time to ferment food contents and produce hydrogen sulfide gas is a plausible hypothesis, but it has not been confirmed in a direct clinical study and should be understood as such.^[18] Diarrhoea may reflect altered gut motility and changes in intestinal transit time.

Phase 2 trial data represent a relatively small and selected population studied over a defined period. Phase 3 results from the TRIUMPH and TRANSCEND programmes, including TRANSCEND-T2D-1 and data from the TRIUMPH obesity trials, have since provided safety and tolerability information across larger and more diverse populations, and further results from these programmes continue to be reported. Rates and severity of individual symptoms varied by dose, and most gastrointestinal events were described as mild to moderate in intensity.^[6][7] These findings come from trial participants under close clinical supervision and cannot be generalised to the wider population.

When should you be concerned about digestive symptoms?

Severe or persistent abdominal pain, prolonged diarrhoea, repeated vomiting or signs of dehydration require prompt medical attention. Trial participants should report adverse events to their trial team; sudden severe abdominal pain warrants immediate A&E attendance.

Persistent or severe digestive symptoms, including prolonged diarrhoea, repeated vomiting, or significant abdominal pain, always warrant medical attention, regardless of the medicine involved. If you are a participant in a retatrutide clinical trial and experience these symptoms, you should report them to your trial team promptly, as the study protocol will specify how adverse events are managed and recorded. If you need emergency or urgent care, tell the clinicians treating you that you are taking part in a clinical trial and show them your participant card or trial contact details, as this may affect how your care is managed. Suspected side effects of a medicine you are taking outside a clinical trial can be reported to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk; if you are in a trial, report to your study team or trial sponsor in the first instance.

Severe or persistent abdominal pain, particularly pain that radiates to the back, should be assessed by a clinician without delay, as acute pancreatitis has been reported in association with GLP-1 receptor agonist medicines.^[4][21] The UK SmPCs for authorised medicines in this class note that post-marketing reports of pancreatitis, including necrotising pancreatitis and cases with fatal outcomes, have been received.^[4][5] If you develop sudden, severe abdominal pain, attend your nearest A&E or call 999. For urgent but non-emergency concerns, NHS 111 can provide advice.

Dehydration is a practical risk with persistent diarrhoea and vomiting. Signs of dehydration include dizziness, reduced urination, dry mouth and confusion. If you are unable to keep fluids down or symptoms continue beyond 24 to 48 hours, contact your GP or, if outside surgery hours, call NHS 111. Do not attempt to self-manage severe or worsening symptoms without clinical guidance.

If you are a trial participant and you become pregnant, think you may be pregnant, or are planning a pregnancy, contact your trial team immediately. Clinical trials for investigational medicines typically exclude pregnancy and breastfeeding, and the protocol will set out the steps to follow, including any requirements around contraception during and after the trial.

What have clinical trials reported about managing gastrointestinal effects?

Gradual dose escalation was the primary management strategy in retatrutide trials, with gastrointestinal events most frequent during escalation phases. Trial participants were also advised on smaller meals, avoiding high-fat foods and staying well hydrated.

Clinical trial protocols for retatrutide, as with other medicines in the GLP-1 receptor agonist class, have used gradual dose escalation as the primary strategy for reducing the burden of gastrointestinal side effects in participants. In the Phase 2 trial (Jastreboff et al., 2023), gastrointestinal events were most frequent during escalation phases rather than at stable maintenance doses, a pattern consistent with findings from trials of other authorised medicines in the same class.

Trial participants were advised on dietary approaches to reduce symptom burden, including eating smaller, more frequent meals, avoiding high-fat or heavily spiced foods, and reducing alcohol intake. These measures are consistent with general guidance offered to patients using authorised GLP-1 receptor agonist medicines, as reflected in NHS patient-facing information and the UK patient information leaflets for Wegovy and Mounjaro. Staying well hydrated was also emphasised, particularly when diarrhoea was present.

It is important to note that management strategies described in trial reports apply to participants under close clinical supervision within a defined protocol. They do not constitute prescribing guidance for general use, and retatrutide remains available only within an authorised clinical trial. Phase 3 data from the TRIUMPH and TRANSCEND programmes, including TRANSCEND-T2D-1 and the TRIUMPH obesity trials, have provided updated tolerability information across broader populations; further results from these programmes are expected as the trials complete. Anyone experiencing gastrointestinal symptoms in the context of any licensed weight-management medicine should discuss them with their prescribing clinician rather than adjusting their treatment independently.

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