Rybelsus (semaglutide) is an oral glucagon-like peptide-1 (GLP-1) receptor agonist licensed in the UK for treating type 2 diabetes mellitus. Whilst it can lead to weight reduction as a secondary benefit, Rybelsus is not approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for weight loss in individuals without diabetes. Men with type 2 diabetes who are overweight or obese may experience weight loss through its effects on appetite suppression and delayed gastric emptying. This article explores how Rybelsus works, who can take it, potential side effects, and alternative weight management options available to men in the UK.

What Is Rybelsus and How Does It Work for Weight Loss?

Rybelsus (semaglutide) is an oral medication licensed in the UK primarily for the treatment of type 2 diabetes mellitus. It belongs to a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists. Importantly, Rybelsus is not licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) for weight loss in individuals without diabetes. It is also not indicated for type 1 diabetes or the treatment of diabetic ketoacidosis.

The mechanism of action centres on mimicking the naturally occurring hormone GLP-1, which is released by the gut in response to food intake. Semaglutide works by:

• Enhancing insulin secretion in a glucose-dependent manner, which helps regulate blood sugar levels

• Suppressing glucagon release, thereby reducing hepatic glucose production

• Slowing gastric emptying, which prolongs the sensation of fullness after meals

• Acting on appetite centres in the brain, particularly the hypothalamus, to reduce hunger and overall caloric intake

It is this combination of delayed gastric emptying and central appetite suppression that contributes to weight reduction. In the PIONEER clinical trials involving people with type 2 diabetes, participants taking Rybelsus experienced weight loss ranging from 2.3-4.4 kg over 26-52 weeks, depending on the dose (7mg or 14mg). However, it is important to note that weight loss is considered a secondary benefit rather than the primary indication for prescribing Rybelsus in the UK. Men seeking weight management should discuss with their GP whether this medication is appropriate, particularly if they have type 2 diabetes.

Who Can Take Rybelsus for Weight Management in the UK?

In the UK, Rybelsus is licensed exclusively for adults with type 2 diabetes as an adjunct to diet and exercise. It is not currently approved by the MHRA as a standalone weight-loss treatment for individuals without diabetes. However, clinicians may occasionally consider its use off-label in specific circumstances, particularly when a patient has obesity alongside other metabolic risk factors.

According to NICE Clinical Guideline 189 on obesity management, pharmacological interventions for weight management are generally recommended for adults with:

• A body mass index (BMI) of 30 kg/m² or above, or

• A BMI of 27 kg/m² or above with associated comorbidities such as hypertension, dyslipidaemia, or obstructive sleep apnoea

For men specifically, there is no evidence suggesting that Rybelsus works differently based on sex, though body composition, hormonal factors, and baseline metabolic rate may influence individual responses. Men with type 2 diabetes who are overweight or obese are the most appropriate candidates for Rybelsus under current UK prescribing guidelines.

Important safety considerations include:

• Not recommended for patients under 18 years of age

• Use with caution in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2

• Use with caution in severe gastrointestinal disease, including gastroparesis

• Not indicated for type 1 diabetes or diabetic ketoacidosis

• Use with caution in renal impairment, particularly severe impairment (eGFR <30 ml/min/1.73m²)

• Not recommended during pregnancy or breastfeeding

• Monitor for diabetic retinopathy in patients with pre-existing disease

Men considering Rybelsus should have a thorough consultation with their GP or an endocrinologist. A comprehensive assessment including BMI, HbA1c, cardiovascular risk, and lifestyle factors is essential before initiating treatment. Self-prescribing or obtaining Rybelsus without medical supervision is strongly discouraged due to potential safety risks.

Side Effects and Safety Considerations for Men

Like all medications, Rybelsus can cause side effects, and men should be aware of both common and serious adverse reactions before starting treatment. The most frequently reported side effects are gastrointestinal in nature and tend to be dose-dependent, often improving over time as the body adjusts.

Very common side effects (affecting more than 1 in 10 people) include:

• Nausea — often most pronounced during the first few weeks

• Diarrhoea

Common side effects (affecting up to 1 in 10 people) include:

• Vomiting

• Abdominal pain or discomfort

• Decreased appetite, which, whilst contributing to weight loss, may be unpleasant

• Constipation

• Dyspepsia (indigestion)

• Flatulence

Less common but notable side effects include:

• Hypoglycaemia (low blood sugar), particularly if Rybelsus is used alongside insulin or sulfonylureas — consider reducing the dose of these medications when starting Rybelsus

• Fatigue and dizziness

• Gallbladder disorders, including cholecystitis and cholelithiasis

Serious adverse effects requiring immediate medical attention include:

• Acute pancreatitis — characterised by severe, persistent abdominal pain radiating to the back. Stop Rybelsus immediately and seek urgent medical care if pancreatitis is suspected

• Severe allergic reactions such as anaphylaxis

• Diabetic retinopathy complications in those with pre-existing eye disease — attend regular eye screening and report any visual changes promptly

• Acute kidney injury, especially in the context of dehydration from vomiting or diarrhoea

Important drug interactions to be aware of:

• Warfarin — monitor INR more frequently when starting or stopping Rybelsus

• Levothyroxine — monitor thyroid function tests as thyroid hormone exposure may increase

• Other oral medications — take at least 30 minutes after Rybelsus to avoid reduced absorption

Men should contact their GP or call NHS 111 if they experience persistent vomiting, severe abdominal pain, or signs of dehydration. There is no evidence linking Rybelsus to male-specific side effects such as reduced testosterone or erectile dysfunction. Regular monitoring of renal function, HbA1c, and body weight is recommended throughout treatment.

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed above. You can also report side effects directly via the Yellow Card Scheme at yellowcard.mhra.gov.uk.

How to Take Rybelsus: Dosage and Practical Guidance

Rybelsus is taken orally once daily, which distinguishes it from other GLP-1 receptor agonists that require subcutaneous injection. Proper administration is crucial for optimal absorption and efficacy, as the bioavailability of oral semaglutide is relatively low and highly sensitive to food and fluid intake.

Dosage schedule:

• Starting dose: 3 mg once daily for 30 days — this initial phase allows the body to adjust and minimises gastrointestinal side effects

• Maintenance dose: After 30 days, increase to 7 mg once daily

• Maximum dose: If additional glycaemic control or weight loss is needed after at least 30 days on 7 mg, the dose may be increased to 14 mg once daily

Administration instructions (critical for absorption):

• Take Rybelsus first thing in the morning on an empty stomach

• Swallow the tablet whole with no more than 120 ml (half a glass) of plain water

• Do not crush, chew, or split the tablet

• Wait at least 30 minutes before eating, drinking (other than water), or taking other oral medications

• Taking Rybelsus with food or excessive fluid significantly reduces absorption

• Waiting longer than 30 minutes before eating or drinking may improve absorption

• If less than 30 minutes elapse before eating, the absorption will be reduced

Practical tips:

• Set a daily alarm to establish a consistent routine

• Prepare the tablet and water the night before to streamline your morning

• If you miss a dose, skip it and resume the next day — do not double up

• Limit alcohol, particularly if experiencing nausea or vomiting, and maintain adequate hydration

• Take other oral medicines after the 30-minute waiting period to avoid reduced absorption of either medication

Attend regular follow-up appointments (typically every 3–6 months) to monitor weight, HbA1c, and tolerability. If weight loss plateaus or side effects become intolerable, discuss alternative strategies with your healthcare provider. Never adjust the dose without medical guidance, as improper use may increase the risk of adverse effects or reduce efficacy.

Alternatives to Rybelsus for Male Weight Loss

For men seeking weight management solutions in the UK, several alternatives to Rybelsus exist, both pharmacological and non-pharmacological. The choice depends on individual health status, BMI, comorbidities, and personal preferences.

Pharmacological alternatives:

• Orlistat — available over the counter in the UK (as Alli 60 mg) and on prescription (Xenical 120 mg). It works by inhibiting pancreatic lipase, reducing dietary fat absorption by approximately 30%. Common side effects include oily stools and flatulence, particularly with high-fat meals. NICE Clinical Guideline 189 recommends orlistat for adults with a BMI ≥28 kg/m² with risk factors or ≥30 kg/m² without.

• Wegovy (injectable semaglutide) — a higher-dose formulation of semaglutide specifically licensed for weight management. Administered once weekly via subcutaneous injection, it has demonstrated greater weight loss (average 10–15% body weight) compared to oral semaglutide. According to NICE Technology Appraisal 875, Wegovy is recommended for adults with a BMI of ≥35 kg/m² with at least one weight-related comorbidity, or ≥30 kg/m² for people from certain ethnic groups, and must be prescribed within specialist weight management services for a maximum of 2 years.

• Saxenda (liraglutide) — another GLP-1 receptor agonist given as a daily injection. NICE Technology Appraisal 664 recommends it for adults with a BMI ≥35 kg/m² with non-diabetic hyperglycaemia and at least one weight-related comorbidity, or ≥30 kg/m² for people from certain ethnic groups. It must be prescribed by specialist tier 3 weight management services and continued only if at least 5% weight loss is achieved at 12 weeks.

• Mounjaro (tirzepatide) — a dual GIP/GLP-1 receptor agonist approved in the UK for type 2 diabetes. While showing promising weight-loss results in clinical trials, it is not currently licensed specifically for obesity management in the UK.

Non-pharmacological approaches remain the cornerstone of weight management:

• Dietary modification — evidence-based approaches include calorie restriction (500–600 kcal deficit), Mediterranean diet, or very low-calorie diets (VLCDs) under supervision

• Physical activity — NICE recommends at least 150 minutes of moderate-intensity aerobic activity weekly, plus resistance training

• Behavioural therapy — cognitive behavioural therapy (CBT) and motivational interviewing can address psychological barriers to weight loss

• Bariatric surgery — NICE recommends considering this for people with a BMI ≥40 kg/m² or ≥35 kg/m² with weight-related comorbidities (with lower thresholds for people of Asian family origin). Procedures such as gastric bypass or sleeve gastrectomy offer substantial, sustained weight loss

Men should discuss these options with their GP or a specialist weight management service. A multidisciplinary approach combining lifestyle modification with appropriate pharmacotherapy typically yields the best long-term outcomes. There is no evidence suggesting that any single medication is superior for men specifically, though individual response varies based on metabolic health, adherence, and concurrent conditions.

Frequently Asked Questions