Cagrilintide and retatrutide for men represent two of the most closely watched investigational medicines in obesity and metabolic medicine. Both are injectable peptide-based therapies targeting multiple hormonal pathways — cagrilintide as a long-acting amylin analogue, and retatrutide as a triple receptor agonist acting on GLP-1, GIP, and glucagon receptors. For men, these treatments are particularly relevant given the links between obesity, low testosterone, cardiovascular risk, and erectile dysfunction. Neither medicine is currently licensed in the UK, but early clinical trial data are promising. This article explains how they work, what the evidence shows, and what men should do next.

What Cagrilintide and Retatrutide Are and How They Work

Cagrilintide is a long-acting amylin analogue that promotes satiety and slows gastric emptying, while retatrutide is a triple agonist targeting GLP-1, GIP, and glucagon receptors to reduce appetite, enhance insulin secretion, and increase energy expenditure.

Cagrilintide and retatrutide are two investigational medicines being developed primarily for the treatment of obesity and type 2 diabetes. Both belong to a new generation of injectable peptide-based therapies that work by targeting multiple hormonal pathways simultaneously, offering potentially greater metabolic benefits than earlier single-receptor agents.

Cagrilintide is a long-acting amylin analogue. Amylin is a hormone naturally co-secreted with insulin from the pancreatic beta cells. It helps regulate appetite, slow gastric emptying, and reduce post-meal blood glucose spikes. Cagrilintide mimics these effects, promoting satiety and reducing caloric intake. It is most often studied in combination with semaglutide (a GLP-1 receptor agonist) in a fixed-dose combination known as CagriSema, investigated in the REDEFINE trial programme.

Retatrutide is a triple hormone receptor agonist, acting on three receptors simultaneously:

• GLP-1 (glucagon-like peptide-1) — reduces appetite and slows gastric emptying

• GIP (glucose-dependent insulinotropic polypeptide) — enhances insulin secretion and may improve fat metabolism

• Glucagon receptor — increases energy expenditure and promotes fat breakdown

It is worth noting that glucagon receptor agonism can, in isolation, raise blood glucose levels; however, in the context of retatrutide's triple-agonist design, this effect is counterbalanced by the concurrent GLP-1 and GIP activity, resulting in a net improvement in glycaemic control.

Early phase 2 clinical data, including a 2023 publication in the New England Journal of Medicine, suggest retatrutide may produce substantial weight loss. Cross-trial comparisons with dual-agonist agents such as tirzepatide are exploratory only — no head-to-head trials have been conducted — and should be interpreted with caution.

Both medicines are administered as subcutaneous injections, typically once weekly, and are still undergoing large-scale clinical trials. Neither is currently licensed for routine clinical use in the UK.

Approved Uses and Current Clinical Evidence in the UK

Neither cagrilintide nor retatrutide is licensed by the MHRA or EMA; both remain in phase 2 and phase 3 trials, and NHS access is not currently possible outside of registered clinical research.

At the time of writing, neither cagrilintide nor retatrutide has received marketing authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) or the European Medicines Agency (EMA) for use in the United Kingdom. Both medicines remain in active clinical development, with phase 2 and phase 3 trials ongoing.

For cagrilintide, the most significant trial programme involves its combination with semaglutide (CagriSema), investigated in the REDEFINE trial series. Interim data from REDEFINE 1 have suggested meaningful body weight reductions in adults with obesity over 68 weeks, comparing favourably with semaglutide alone.^[12][13] Readers should note that final peer-reviewed results from this programme are still emerging, and specific percentage figures may change as the full dataset is published. These findings are promising but have not yet translated into a licensed product.

For retatrutide, phase 2 data published in the New England Journal of Medicine (2023) demonstrated substantial mean weight reductions over 48 weeks in adults with obesity — among the highest figures reported for any pharmacological agent to date.^[4] Phase 3 trials (the TRIUMPH programme) are currently underway, with results anticipated in the coming years.^[6][10] Trial status can be verified via ClinicalTrials.gov and the EU Clinical Trials Register.

NICE has not yet issued guidance on either agent, as appraisal processes are typically initiated only after regulatory approval, although scoping can occur earlier. Clinicians and patients should be aware that access to these medicines outside of clinical trials is not currently possible through NHS pathways. Participation in a registered clinical trial remains the only legitimate route to access these treatments in the UK at present.

How These Medicines May Affect Men Specifically

In men, significant weight loss from these agents may improve obesity-related hypogonadism and testosterone levels, though no agent-specific data on testosterone or erectile function outcomes are yet available for either medicine.

Obesity and metabolic disease carry particular health burdens for men, including increased risk of type 2 diabetes, cardiovascular disease, obstructive sleep apnoea, and hypogonadism (low testosterone). Excess adipose tissue — particularly visceral fat — is associated with reduced testosterone levels and impaired fertility in men, making effective weight management especially relevant to male health.

While neither cagrilintide nor retatrutide has been studied exclusively in male populations, available trial data include substantial numbers of male participants. There is no evidence to suggest that the fundamental mechanisms of action differ between sexes. However, some sex-specific considerations are worth noting:

• Testosterone and hormonal health: Significant weight loss achieved through these agents may lead to improvements in testosterone levels in men with obesity-related hypogonadism. Systematic reviews and meta-analyses in the endocrinology literature indicate that visceral fat reduction decreases peripheral aromatisation of testosterone to oestrogen, which can improve the hormonal profile. These findings are drawn from the broader weight-loss literature; no agent-specific data for cagrilintide or retatrutide on testosterone outcomes are yet available.

• Erectile dysfunction: Obesity is a recognised risk factor for erectile dysfunction.^[14][15] Weight loss interventions may improve vascular function and sexual health; however, there is no direct clinical evidence yet linking cagrilintide or retatrutide specifically to improvements in erectile function.

• Muscle mass: Men may be more concerned about lean muscle preservation during rapid weight loss. The glucagon receptor activity in retatrutide increases energy expenditure, and its effects on muscle mass relative to fat mass in men are still being characterised in ongoing trials. Engaging in regular resistance exercise and maintaining adequate dietary protein intake are generally recommended alongside any weight-loss intervention to help preserve lean mass — consistent with NICE obesity management guidance (CG189).

Men considering these treatments should discuss their full medical history, including any history of hypogonadism or fertility concerns, with their clinician.

Dosage, Administration, and What to Expect

Both medicines are given as once-weekly subcutaneous injections with gradual dose titration; these are trial protocols only, as no licensed dosing schedules or UK SmPCs exist for either agent.

Both cagrilintide and retatrutide are administered as subcutaneous injections, typically once weekly. In clinical trials, doses are escalated gradually over several weeks to improve tolerability — a process known as dose titration. This approach is consistent with other agents in this class, such as semaglutide and tirzepatide.

For cagrilintide (in combination with semaglutide as CagriSema), trial protocols have used a structured titration schedule over several weeks to reach the maintenance dose. For retatrutide, the 2023 New England Journal of Medicine phase 2 trial used doses of up to 12 mg weekly, with a structured escalation schedule beginning at lower doses and increasing incrementally over a period of weeks.^[4][5] Readers should note that these figures reflect specific trial protocols and may not represent the doses used in ongoing phase 3 studies or any future licensed product.

Patients in trials typically begin to notice appetite suppression and early weight loss within the first few weeks of treatment. Meaningful weight reduction is generally observed by weeks 12 to 16, with maximum weight loss tending to occur later in the treatment period, depending on the agent and dose.

Because these medicines are not yet licensed, there are no approved patient information leaflets or UK Summary of Product Characteristics (SmPC) available. Dosage information provided here is drawn from published clinical trial protocols and should not be used as a guide for self-administration. Any use outside of a supervised clinical trial setting would be inappropriate and potentially unsafe.

Side Effects, Risks, and Safety Considerations

The most common side effects are gastrointestinal — nausea, vomiting, and diarrhoea — with more serious risks including pancreatitis, gallbladder disease, and elevated resting heart rate; suspected side effects should be reported via the MHRA Yellow Card scheme.

The side effect profiles of cagrilintide and retatrutide are broadly consistent with other incretin-based therapies, reflecting their shared mechanisms of action. The most commonly reported adverse effects in clinical trials are gastrointestinal in nature, particularly during dose escalation.

Common side effects include:

• Nausea and vomiting

• Diarrhoea or constipation

• Reduced appetite (which is also a therapeutic effect)

• Injection site reactions (redness, bruising, or mild discomfort)

These effects are typically mild to moderate and tend to resolve as the body adjusts to the medication. Slower dose titration can help minimise their severity.

More serious risks to be aware of include:

• Pancreatitis: As with other GLP-1 receptor agonists, there is a theoretical and observed risk of acute pancreatitis. Patients should seek urgent medical attention if they develop severe, persistent abdominal pain.

• Thyroid C-cell findings: Preclinical studies in rodents with GLP-1 receptor agonists have identified C-cell hyperplasia. The relevance of these findings to humans is not established, and this is not classified as a formal contraindication in UK or EU labelling (unlike in the United States). Individuals with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia type 2 (MEN2) should discuss this with their clinician before considering any GLP-1–based therapy, and should be alert to symptoms such as a neck lump, hoarseness, or difficulty swallowing.

• Gallbladder disease: Incretin-based therapies have been associated with an increased risk of cholelithiasis (gallstones) and cholecystitis (gallbladder inflammation), as noted in the UK SmPCs for licensed comparators such as semaglutide and tirzepatide.^[17][18] Patients should report persistent upper abdominal pain to their clinician.

• Diabetic retinopathy: Rapid improvement in blood glucose control has been associated with early worsening of diabetic retinopathy in some patients.^[20][21] Men with pre-existing retinopathy should be monitored appropriately.

• Heart rate: Increases in resting heart rate have been observed with incretin-based agents. This should be considered in men with pre-existing cardiac conditions.

• Hypoglycaemia: Risk is low when used without insulin or sulphonylureas, but men with type 2 diabetes on combination therapy should monitor blood glucose carefully.

• Renal function: Dehydration secondary to gastrointestinal side effects can impair renal function, particularly in those with pre-existing kidney disease.

Men should contact their GP or trial clinician promptly if they experience severe abdominal pain, persistent vomiting, signs of dehydration, or any unexpected symptoms.

Reporting side effects: If you experience a suspected side effect from any medicine — including within a clinical trial — you can report it to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk or through the Yellow Card app. Your report helps improve the safety monitoring of medicines in the UK.

Availability on the NHS and Next Steps for Treatment

Neither medicine is available on the NHS; men should seek participation in a registered clinical trial via NIHR Be Part of Research, or discuss currently NICE-approved treatments such as semaglutide or tirzepatide with their GP.

Currently, neither cagrilintide nor retatrutide is available through the NHS. Both medicines are unlicensed in the UK, meaning they cannot be prescribed through standard NHS or private prescribing routes. Purchasing these agents from unregulated online sources carries significant safety risks, including exposure to counterfeit or incorrectly dosed products, and is strongly discouraged.

For men who are interested in accessing these treatments, the most appropriate route is participation in a registered clinical trial. The recommended starting point for finding UK trials is:

• NIHR Be Part of Research (bepartofresearch.nihr.ac.uk) — the UK's public-facing portal for finding and joining clinical research studies

• ClinicalTrials.gov and the EU Clinical Trials Register — international registries of ongoing studies, including the REDEFINE and TRIUMPH programmes

• Referral via a GP or specialist to a trial centre

In the meantime, men with obesity or type 2 diabetes should be aware that NICE-approved treatments are already available and may offer meaningful clinical benefit:

• Semaglutide (Wegovy®) is approved by NICE (TA875) for weight management in adults with a BMI ≥35 kg/m² (or lower thresholds for certain ethnic groups) and at least one weight-related comorbidity, subject to specialist tier service criteria and duration requirements.^[22]

• Tirzepatide (Mounjaro®) has received NICE approval for type 2 diabetes and for weight management, again subject to specific eligibility criteria and specialist service requirements. Readers should consult the relevant NICE technology appraisals for full details.

Men concerned about their weight, metabolic health, or related conditions such as low testosterone or cardiovascular risk should speak with their GP in the first instance. A structured assessment can determine eligibility for existing licensed treatments, referral to a specialist weight management service (in line with NICE CG189), or enrolment in a clinical trial. Staying informed through reputable sources such as the NHS website, NICE (nice.org.uk), and the MHRA (gov.uk/mhra) is the safest approach as this rapidly evolving field continues to develop.

Frequently Asked Questions