Cagrilintide and Retatrutide for Men

Cagrilintide and retatrutide are investigational medicines being studied in clinical trials for obesity and type 2 diabetes, but neither holds a UK marketing authorisation. Understanding what cagrilintide and retatrutide are for men requires clarity on their distinct mechanisms, the current state of clinical trial evidence, and their regulatory status. This article explains how each medicine works, what trial data involving male participants currently show, what side effects have been reported, and why both agents remain available only within authorised research settings in the UK.

What are cagrilintide and retatrutide, and how do they work?

Cagrilintide is a long-acting amylin analogue that promotes satiety via brain amylin receptors, while retatrutide is a triple GLP-1, GIP and glucagon receptor agonist that reduces appetite and may increase energy expenditure. Neither is authorised in the UK.

Cagrilintide and retatrutide are investigational medicines being studied for the treatment of obesity and type 2 diabetes, and neither holds a UK marketing authorisation. Cagrilintide is a long-acting analogue of amylin, a hormone produced by the pancreas that helps regulate appetite, gastric emptying and blood glucose.^[1][2] It is being investigated both as a standalone agent and in a fixed-dose combination with semaglutide, known as CagriSema. Retatrutide is a triple receptor agonist that simultaneously activates receptors for glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon.^[5][6] By engaging all three pathways, retatrutide aims to reduce appetite, increase energy expenditure and improve metabolic markers.

Both agents belong to a broader class of incretin-based and metabolic hormone therapies that have attracted significant research interest following the clinical success of licensed GLP-1 receptor agonists. Their mechanisms differ from one another: cagrilintide works primarily through amylin receptor pathways in the brain to promote satiety, while retatrutide's glucagon receptor component may contribute to increased energy expenditure; this thermogenic effect has been observed in preclinical and early clinical studies of glucagon receptor agonism, though the clinical magnitude and its comparison with other agonist classes remain to be established in larger trials.^[7][8] These are distinct pharmacological profiles, and the two medicines are not used together in current trials.

Because neither medicine is authorised in the UK, they are available only within the context of authorised clinical trials. Any product sold online claiming to be cagrilintide or retatrutide is not a licensed medicine and may be falsified or unsafe. Men interested in licensed weight-management treatments should speak with their GP.

What do clinical trials say about these drugs in male participants?

Trial data include male participants but are reported for overall study populations rather than as sex-specific analyses; full Phase 3 results for both medicines had not been completely published at the time of writing.

Clinical trial data for both cagrilintide and retatrutide include male participants, though published results are reported at the level of the overall trial population rather than as sex-specific subgroup analyses in most cases. For retatrutide, a Phase 2 trial published in the New England Journal of Medicine in 2023 enrolled adults with obesity and reported reductions in body weight over 48 weeks across the trial population; the authors reported these findings for the overall study group, and the figures should be interpreted in the context of that specific trial design, population and duration rather than as a general prediction of effect.^[5][6] The ongoing Phase 3 programme, which includes the TRIUMPH-1 to TRIUMPH-4 studies and the TRANSCEND-T2D-1 trial (the latter published in The Lancet), is evaluating retatrutide across broader populations including people with type 2 diabetes, and these studies include male participants.^[9][10] Full Phase 3 results across the TRIUMPH programme had not been completely published at the time of writing, and readers should consult current literature for the latest data.

For cagrilintide, Phase 2 data have examined the medicine both alone and in combination with semaglutide (CagriSema), with trials reporting reductions in body weight and improvements in glycaemic markers in mixed-sex populations.^[12][13] Phase 3 trials for CagriSema are under way, though results are not yet fully published at the time of writing.

It is important to note that trial findings describe outcomes in research populations under controlled conditions and cannot be taken as predictions of what any individual would experience. Men with obesity-related conditions such as type 2 diabetes, hypertension or obstructive sleep apnoea have been included in trial populations, but sex-stratified efficacy data are not consistently reported in primary publications, and these studies are not powered to detect differences between sexes. Researchers and clinicians reviewing these medicines will need to await full Phase 3 reporting before drawing conclusions about outcomes specific to men.

What is the regulatory status of these medicines in the UK?

Neither cagrilintide nor retatrutide holds a UK marketing authorisation from the MHRA, and neither can be legally prescribed or supplied outside an authorised clinical trial.

Neither cagrilintide nor retatrutide holds a marketing authorisation in the UK, and neither has been recommended by NICE for NHS use. The Medicines and Healthcare products Regulatory Agency (MHRA) authorises medicines for use in the UK, and until that authorisation is granted, neither medicine can be legally prescribed or supplied outside an authorised clinical trial. No timeline for UK authorisation can be given for either agent.

Retatrutide is being developed by Eli Lilly and is currently in Phase 3 clinical trials globally. Cagrilintide and the CagriSema combination are being developed by Novo Nordisk and are also in late-stage clinical development. Regulatory submissions to the MHRA or the European Medicines Agency (EMA) have not been publicly confirmed as complete for either product at the time of writing, and marketing authorisation decisions follow a formal review process that cannot be predicted in advance.

For context, the licensed landscape for weight management in the UK includes, among others, semaglutide (Wegovy, available in doses up to 2.4 mg and 7.2 mg weekly), tirzepatide (Mounjaro, authorised by the MHRA both for type 2 diabetes and for chronic weight management), liraglutide (Saxenda) and orforglipron (Foundayo).^[18][19] These medicines are recommended through NICE technology appraisals, though local commissioning decisions are made by Integrated Care Boards (ICBs) and NHS availability is not automatic following a NICE recommendation. Men who wish to discuss licensed options should do so with their GP.

Are there any side effects men should know about?

The most commonly reported adverse events in trials are gastrointestinal, including nausea, vomiting and diarrhoea, and are generally dose-dependent and most prominent during dose escalation.

Both cagrilintide and retatrutide have shown gastrointestinal side effects as the most commonly reported adverse events in clinical trials, consistent with the broader class of metabolic hormone therapies. These include nausea, vomiting, diarrhoea and constipation, and they have generally been reported as dose-dependent and most prominent during dose escalation phases in trials.

For retatrutide specifically, the Phase 2 trial reported injection-site reactions and gastrointestinal events as the most frequent adverse effects. Because retatrutide activates glucagon receptors in addition to GLP-1 and GIP pathways, its side-effect profile may differ from that of dual or single agonists, though direct comparisons between trials are not valid given differences in study design, population and duration. The UK SmPC for licensed GLP-1 receptor agonists notes that acute pancreatitis has been reported, including post-marketing reports of necrotising pancreatitis and reports with a fatal outcome, though no risk magnitude is established.^[24] Whether this signal extends to retatrutide or cagrilintide will require further data from ongoing trials.

Men participating in clinical trials for either medicine should report any adverse events promptly to the trial team under the study protocol. Trial participants are also advised to carry their participant identification card at all times and to show it to any emergency clinician, informing them of the investigational product being received and following any site-specific instructions provided by the trial team. If a participant experiences severe abdominal pain, persistent vomiting or signs of an allergic reaction, they should contact their trial team immediately. For any life-threatening emergency, call 999 or go to the nearest accident and emergency department. For urgent non-emergency advice, NHS 111 is available.

Suspected side effects of any medicine can be reported to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk; this applies to licensed medicines a patient is taking outside a trial setting. Adverse events occurring within a clinical trial should be reported to the trial team or sponsor as set out in the study protocol.

Why are these treatments only available in clinical trials right now?

Both medicines have not completed the regulatory review required for MHRA authorisation; Phase 3 trials are needed to establish the full safety and efficacy evidence base before a marketing authorisation can be granted.

Cagrilintide and retatrutide are only available in authorised clinical trials because they have not yet completed the full regulatory review process required for a UK marketing authorisation. Before the MHRA can authorise a medicine, the developer must submit a comprehensive dossier of evidence covering quality, safety and efficacy across the intended population. Phase 3 trials are designed to generate this evidence at scale, and their completion and analysis are prerequisites for a regulatory submission.

Clinical trials also serve an important safety function. Even when Phase 2 data are encouraging, larger and longer trials are needed to identify less common adverse events, to characterise the safety profile in subgroups (including men with specific comorbidities), and to establish the benefit-risk balance that regulators require. For investigational medicines in the obesity and metabolic disease space, trials typically run for one to two years or longer to capture sustained outcomes and any delayed safety signals.

Men who are interested in participating in a clinical trial for either medicine should discuss eligibility with their GP or a specialist, who can advise on whether any relevant trials are recruiting in their area. Legitimate recruiting studies can be found through NHS Be Part of Research (bepartofresearch.nihr.ac.uk) and ClinicalTrials.gov, which lists the TRIUMPH and REDEFINE programmes among others. Participation in a clinical trial is voluntary and subject to strict inclusion and exclusion criteria, which commonly include factors such as age, body mass index, existing medical conditions and current medications. It is not possible to obtain cagrilintide or retatrutide outside a trial setting in the UK, and any online source claiming to supply either medicine is not offering a licensed product and may pose a serious risk to health.

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