Retatrutide is an investigational triple incretin receptor agonist generating significant interest for obesity and type 2 diabetes management. Understanding what to take with retatrutide — including appropriate nutritional support, lifestyle measures, and medication considerations — is essential for anyone participating in a clinical trial. As retatrutide remains unlicensed in the UK and is not approved by the MHRA or EMA, it is only accessible through regulated clinical trials. This article outlines the key supplements, dietary strategies, potential drug interactions, and substances to avoid, alongside guidance on when to consult your GP or specialist.

What Is Retatrutide and How Does It Work?

Retatrutide is an investigational injectable triple incretin receptor agonist that simultaneously activates GLP-1, GIP, and glucagon receptors, enhancing insulin secretion, suppressing appetite, and potentially increasing energy expenditure. It is not yet approved by the MHRA or EMA.

Retatrutide is an investigational injectable medication currently undergoing clinical trials for the management of obesity and type 2 diabetes. It belongs to a novel class of agents known as triple incretin receptor agonists, meaning it simultaneously activates three hormone receptors: glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. This triple mechanism distinguishes it from existing approved therapies such as semaglutide (a GLP-1 receptor agonist) and tirzepatide (a dual GIP/GLP-1 agonist).

By activating GLP-1 receptors, retatrutide is thought to enhance insulin secretion in a glucose-dependent manner, suppress glucagon release, and slow gastric emptying — effects that may contribute to improved blood glucose control and reduced appetite. GIP receptor activation may further support insulin release and, based on preclinical and early human data, could influence fat metabolism, though the precise contribution in humans remains under investigation. Glucagon receptor agonism is hypothesised to increase energy expenditure, which may partly explain the substantial weight loss observed in early-phase trials; however, the net metabolic effects of simultaneously activating and suppressing glucagon-related pathways are still being characterised.

Phase 2 clinical trial data published in 2023 in the New England Journal of Medicine demonstrated that participants receiving the highest dose of retatrutide achieved a mean body weight reduction of approximately 24% over 48 weeks — results that have generated considerable scientific interest. It is important to note that these are phase 2 findings; long-term safety and efficacy data are not yet available. As of 2025, retatrutide has not received approval from the Medicines and Healthcare products Regulatory Agency (MHRA) or the European Medicines Agency (EMA) for routine clinical use in the UK. It remains an experimental therapy, and patients should not attempt to obtain it outside of regulated clinical trial settings. Those interested in participating in a trial can search for eligible studies via the NIHR 'Be Part of Research' portal (bepartofresearch.nihr.ac.uk).

Supplements and Nutrients to Consider Alongside Retatrutide

Reduced food intake during retatrutide treatment raises the risk of deficiencies in protein, vitamin D, B12, calcium, and iron; a food-first approach is recommended, with supplementation guided by a clinician or registered dietitian.

Because retatrutide significantly reduces appetite and slows gastric emptying, individuals participating in clinical trials may consume considerably less food than usual. This reduction in dietary intake can increase the risk of micronutrient deficiencies, making thoughtful nutritional support an important consideration — ideally discussed with a GP, registered dietitian, or trial clinician before making any changes.

Key nutrients to consider include:

• Protein: Reduced caloric intake during significant weight loss can lead to loss of lean muscle mass. Ensuring adequate dietary protein is important; general obesity management guidance (including from the British Dietetic Association and the European Association for the Study of Obesity) typically suggests around 1.2–1.6 g per kg of body weight per day during active weight loss, though this should be reviewed by a clinician for anyone with chronic kidney disease, as higher protein intakes may not be appropriate in that context.

• Vitamin D: Vitamin D deficiency is common in the UK population. UK Government and NHS guidance recommends that most adults consider a daily supplement of 10 micrograms (400 IU) of vitamin D, particularly during autumn and winter months when sunlight exposure is limited. Reduced food intake may further compromise levels.

• Calcium: Adequate calcium intake supports bone health, particularly during periods of significant weight loss. Dairy products, fortified plant-based alternatives, and leafy green vegetables are good dietary sources.

• Vitamin B12: Significantly reduced food intake may lower dietary B12 intake, which is essential for neurological function and red blood cell production. Note that certain commonly used medicines — including metformin and proton pump inhibitors — are established causes of B12 depletion and should be considered when assessing risk. Testing is appropriate if clinically indicated rather than routinely.

• Iron and other minerals: Iron, and to a lesser extent other minerals, may be under-consumed during calorie restriction. Testing should be guided by symptoms and clinical risk rather than performed routinely.

• A standard multivitamin–mineral supplement may be a practical option for individuals whose dietary intake is very restricted, under the guidance of a clinician or dietitian, rather than multiple individual supplements.

A food-first approach is always preferable: prioritising a varied, nutrient-dense diet should be the primary strategy. For cardiovascular health, the NHS recommends eating at least two portions of fish per week, one of which should be oily (such as salmon, mackerel, or sardines), as a source of omega-3 fatty acids; routine omega-3 supplementation is not recommended for primary prevention of cardiovascular disease in UK guidance. It is advisable to avoid self-prescribing high-dose supplements without professional guidance, as excessive intake of certain nutrients (such as fat-soluble vitamins A, D, E, and K) can be harmful. A registered dietitian can provide personalised recommendations based on dietary assessment and blood results.

Dietary and Lifestyle Recommendations While Taking Retatrutide

A nutrient-dense diet with smaller, frequent meals and at least 150 minutes of moderate aerobic activity per week supports retatrutide's effects and helps preserve lean muscle mass during weight loss.

Retatrutide is not a standalone solution; its efficacy is best supported by concurrent dietary and lifestyle modifications. Clinical trial protocols typically incorporate structured dietary counselling alongside the medication, reflecting the broader principle — set out in NICE guidance on obesity management (CG189) and lifestyle weight management services (PH53) — that pharmacological therapies work most effectively as part of a comprehensive programme.

Dietary recommendations:

• Focus on nutrient-dense foods — lean proteins, vegetables, wholegrains, legumes, and healthy fats — to maximise nutritional intake despite reduced appetite.

• Eat smaller, more frequent meals to accommodate slowed gastric emptying and reduce the risk of nausea or bloating, which are common gastrointestinal side effects associated with incretin-based therapies.

• Stay well hydrated, aiming for at least 1.5–2 litres of fluid daily, as reduced food intake can also reduce fluid consumption from food sources. This is particularly important if you experience nausea, vomiting, or diarrhoea.

• Limit ultra-processed foods, refined sugars, and alcohol, which provide poor nutritional value and may worsen gastrointestinal symptoms.

Lifestyle recommendations:

• Engage in regular physical activity in line with UK Chief Medical Officers' guidelines: aim for at least 150 minutes of moderate-intensity aerobic activity (or 75 minutes of vigorous-intensity activity) per week, plus muscle-strengthening activities on at least two days per week. Resistance training is particularly important during significant weight loss to help preserve lean muscle mass.

• If you are taking insulin or a sulphonylurea (such as gliclazide), be aware that increasing physical activity alongside dietary changes can affect blood glucose levels. Seek a medication review and monitor your glucose more closely when making these changes.

• Prioritise sleep hygiene, as poor sleep is independently associated with weight gain and metabolic dysfunction.

• Consider behavioural support such as cognitive behavioural therapy (CBT) or structured weight management programmes, which are recommended within NICE obesity guidelines (CG189, PH53) as adjuncts to pharmacological treatment.

These lifestyle measures not only support the weight loss achieved with retatrutide but also contribute to long-term weight maintenance, which remains a challenge following any pharmacological intervention.

Medications That May Interact With Retatrutide

Retatrutide's effect on gastric emptying can delay absorption of oral medicines including warfarin, levothyroxine, and antiepileptics; it may also increase hypoglycaemia risk when combined with sulphonylureas or insulin.

As retatrutide is still in clinical development, its full drug interaction profile has not been comprehensively established. However, based on its pharmacological mechanisms — particularly its effects on gastric emptying, insulin secretion, and glucagon activity — several clinically relevant interactions warrant consideration.

Oral medications: Slowed gastric emptying, a known effect of GLP-1 receptor agonism, can delay the absorption of orally administered drugs. This is particularly relevant for medications with narrow therapeutic windows, such as warfarin, levothyroxine, and certain antiepileptics. The clinical significance of this effect varies between medicines and individuals. Rather than pre-emptive dose changes, the priority is appropriate monitoring: INR monitoring for warfarin, TSH and clinical assessment for levothyroxine, and drug levels or clinical monitoring for antiepileptics. Patients taking these medicines should inform their prescribing clinician.

Antidiabetic medications: Retatrutide enhances insulin secretion in a glucose-dependent manner. When used alongside sulphonylureas (e.g., gliclazide) or insulin, there may be an increased risk of hypoglycaemia. Dose reductions of these agents may be necessary, and blood glucose monitoring should be intensified.

Antihypertensive and cardiovascular medications: Significant weight loss can lower blood pressure and improve cardiovascular risk factors, potentially necessitating dose reductions in antihypertensive agents to avoid hypotension. This should be reviewed regularly by your clinician.

Renal function and volume-sensitive medicines: Prolonged vomiting or diarrhoea can cause dehydration and may impair kidney function, particularly in people taking ACE inhibitors, angiotensin receptor blockers (ARBs), or diuretics. Renal function should be checked if significant gastrointestinal side effects occur.

Oral contraceptives: Evidence from the tirzepatide Summary of Product Characteristics (SmPC) indicates that delayed gastric emptying may reduce the absorption of oral contraceptive pills during initiation and dose escalation of that medicine. Whether the same applies to retatrutide is not yet known. As a precaution, women of childbearing potential should discuss contraceptive options with their GP or gynaecologist; a non-oral method or additional barrier contraception during initiation and escalation may be advisable until more data are available.

It is essential that any clinician prescribing or monitoring retatrutide — within a trial context — has a full and up-to-date medicines reconciliation list. Patients should never adjust or discontinue existing medications without professional guidance.

What to Avoid When Taking Retatrutide

Alcohol, high-fat and high-sugar foods, unlicensed weight loss products, and skipping meals should be avoided, as these worsen gastrointestinal side effects, increase health risks, and compromise nutritional intake.

Certain substances, behaviours, and practices are best avoided during treatment with retatrutide to minimise side effects, reduce health risks, and support optimal outcomes.

Alcohol: Alcohol consumption should be minimised or avoided. Alcohol is calorie-dense, can worsen nausea (a common side effect of incretin therapies), and may increase the risk of hypoglycaemia in individuals also taking insulin or sulphonylureas. NHS guidance recommends that adults drink no more than 14 units of alcohol per week, spread over at least three days, with alcohol-free days each week.

High-fat and high-sugar foods: These can exacerbate gastrointestinal side effects such as nausea, vomiting, and diarrhoea, which are among the most commonly reported adverse effects in retatrutide trials. Fatty meals in particular may worsen symptoms due to their interaction with delayed gastric emptying.

Unregulated weight loss products: Patients should avoid purchasing unlicensed or counterfeit weight loss injections online. The MHRA has issued repeated warnings about the dangers of falsified GLP-1 receptor agonist products — including counterfeit Ozempic pens — circulating in the UK. There is no legitimate route to obtain retatrutide outside of an approved clinical trial.

Skipping meals entirely: While appetite suppression is a desired effect, completely skipping meals can lead to inadequate nutrient intake, fatigue, and muscle loss. Structured, small meals are preferable to prolonged fasting.

Pregnancy and breastfeeding: Retatrutide is unlicensed and its safety in pregnancy or during breastfeeding has not been established. Clinical trials typically require participants to use effective contraception throughout. If you become pregnant or are planning a pregnancy, inform your trial team immediately. Breastfeeding is not recommended during trial participation. Discuss your options with your GP or trial clinician.

Stopping the medication abruptly without guidance: Discontinuing retatrutide without medical supervision — particularly in a trial context — may lead to weight regain and metabolic deterioration. Any decision to stop treatment should be made in consultation with the supervising clinician.

Ignoring signs of dehydration: Nausea, vomiting, and diarrhoea can cause significant fluid loss. If you are unable to maintain adequate fluid intake, feel dizzy, notice a marked reduction in urine output, or feel generally unwell, seek medical advice promptly.

Guidance From Your GP or Specialist Before Starting Retatrutide

Before starting retatrutide in a trial, your clinician should review your medical history, perform baseline blood tests, assess gallbladder health, reconcile your medicines, and provide contraceptive and side-effect counselling.

Given that retatrutide is not yet licensed for clinical use in the UK, access is currently limited to participants enrolled in regulated clinical trials. If you are interested in retatrutide, the appropriate first step is to speak with your GP, who can advise on eligibility for relevant trials and refer you to specialist obesity or metabolic medicine services where appropriate. Eligible studies can also be searched via the NIHR 'Be Part of Research' portal.

Before starting retatrutide (within a trial setting), your clinician should:

• Conduct a thorough medical history review, including assessment of conditions that may be trial exclusion criteria or require particular caution — for example, a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2). These are not established contraindications in UK SmPCs for currently licensed GLP-1-based medicines (the human risk is unknown), but they are commonly applied as precautionary exclusion criteria in trials based on nonclinical data.

• Perform baseline investigations, including fasting glucose, HbA1c, lipid profile, renal and liver function tests, full blood count, and thyroid function.

• Assess gallbladder health: rapid weight loss and incretin-based therapies are associated with an increased risk of gallstones and gallbladder disease. A baseline assessment and awareness of relevant symptoms is important.

• Review your current medication list in full to identify potential interactions, as outlined above.

• Conduct pregnancy testing where appropriate, provide contraceptive counselling, and advise that breastfeeding should be avoided during trial participation.

• Assess mental health status, as significant dietary restriction and body image changes during weight loss can affect psychological wellbeing.

• Provide clear information about common side effects — particularly nausea, vomiting, diarrhoea, and constipation — and advise on management strategies.

When to seek urgent medical advice during treatment:

• Persistent or severe vomiting or diarrhoea preventing adequate fluid intake, or signs of dehydration (dizziness, reduced urine output, confusion)

• Signs of hypoglycaemia (shakiness, sweating, confusion, palpitations)

• Severe or persistent abdominal pain, which may rarely indicate pancreatitis

• Right upper quadrant pain, fever, or jaundice, which may suggest gallbladder disease

• New or worsening visual changes (particularly in people with pre-existing diabetic retinopathy, as rapid improvement in blood glucose control can occasionally affect the retina)

• Any new or worsening symptoms that concern you

Your GP remains your first point of contact for any health concerns arising during participation in a clinical trial. Open communication between trial investigators and your primary care team is essential for safe, coordinated care.

If you experience a suspected side effect from retatrutide within a trial, this should be reported through the trial's pharmacovigilance process. You may also report suspected adverse reactions directly to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk.

Frequently Asked Questions