Is Rybelsus for Prediabetes? UK Guidance and Evidence

Rybelsus (semaglutide) is an oral GLP-1 receptor agonist licensed in the UK for treating type 2 diabetes, but is Rybelsus for prediabetes an appropriate option? Currently, Rybelsus is not approved for prediabetes management by the MHRA or NICE. Prediabetes, characterised by HbA1c levels of 42–47 mmol/mol, is best managed through intensive lifestyle interventions such as diet, exercise, and weight loss. Whilst emerging research explores GLP-1 agonists in diabetes prevention, evidence specific to oral semaglutide in prediabetes remains limited. This article examines the current evidence, NHS guidance, and alternative strategies for managing prediabetes safely and effectively.

What Is Rybelsus and How Does It Work?

Rybelsus (semaglutide) is an oral medication belonging to a class of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists. It is currently licensed in the UK for the treatment of type 2 diabetes mellitus in adults, typically when diet and exercise alone have not achieved adequate glycaemic control. Rybelsus is the first GLP-1 receptor agonist available in tablet form, offering an alternative to injectable formulations such as Ozempic (also semaglutide) and other GLP-1 analogues.

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

• Enhancing insulin secretion from pancreatic beta cells in a glucose-dependent manner, meaning it stimulates insulin release only when blood glucose levels are elevated

• Suppressing glucagon secretion, which reduces glucose production by the liver

• Slowing gastric emptying, leading to a more gradual rise in blood glucose after meals

• Reducing appetite and food intake, which can contribute to weight loss as a secondary effect (though Rybelsus is not licensed for weight management)

These combined effects help to lower blood glucose levels and improve overall metabolic control. Because insulin secretion is glucose-dependent, the risk of hypoglycaemia (dangerously low blood sugar) is relatively low when Rybelsus is used as monotherapy. However, this risk increases when combined with sulfonylureas or insulin.

It is important to note that Rybelsus is not currently licensed for prediabetes in the UK. Its approved indication is specifically for type 2 diabetes, and prescribing it for prediabetes would be considered off-label use.

Rybelsus must be taken correctly to ensure absorption: on an empty stomach with no more than 120 ml of water, followed by at least 30 minutes before consuming any food, drink or other oral medications.

Evidence for Rybelsus in Prediabetes Management

While Rybelsus is not licensed for prediabetes, there is emerging research exploring whether GLP-1 receptor agonists might help prevent or delay progression from prediabetes to type 2 diabetes. Prediabetes is defined by blood glucose levels that are higher than normal but not yet high enough to meet diagnostic criteria for diabetes—typically an HbA1c of 42–47 mmol/mol (6.0–6.4%) or a fasting plasma glucose of 5.5–6.9 mmol/L in UK practice for identifying those at high risk.

Several clinical trials have investigated GLP-1 receptor agonists in populations with prediabetes or impaired glucose tolerance. For example, the SCALE Obesity and Prediabetes trial with liraglutide 3.0 mg (another GLP-1 agonist, at a higher dose than used for diabetes) demonstrated reduced progression to type 2 diabetes and improvements in weight and cardiovascular risk factors. Similarly, the STEP trials have shown benefits with injectable semaglutide 2.4 mg (Wegovy) in obesity with prediabetes, but this is a different product and dose than Rybelsus.

Specific evidence for oral semaglutide (Rybelsus) in prediabetes remains limited. Most trials have focused on its efficacy in established type 2 diabetes rather than earlier stages of glucose dysregulation.

It is important to emphasise that there is no official regulatory approval or clinical guideline supporting the use of Rybelsus for prediabetes in the UK. The Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have not extended the licence to include prediabetes. Any use in this context would require careful discussion with a healthcare professional and would be considered outside the terms of the marketing authorisation. Patients with prediabetes should be aware that lifestyle interventions remain the cornerstone of evidence-based management, as supported by robust trial data.

NHS and NICE Guidance on Prediabetes Treatment

The National Institute for Health and Care Excellence (NICE) provides clear guidance on the management of prediabetes, which it refers to as non-diabetic hyperglycaemia (NDH) or intermediate hyperglycaemia. According to NICE guideline PH38 (updated in 2017), the primary approach to preventing or delaying type 2 diabetes in people with prediabetes is through intensive lifestyle modification.

NICE recommends that adults identified with prediabetes should be offered:

• Structured education programmes focusing on diet, physical activity, and weight management

• Individualised advice on achieving and maintaining a healthy weight, particularly if overweight or obese

• Regular physical activity, aiming for at least 150 minutes of moderate-intensity exercise per week, in line with UK Chief Medical Officers' guidelines

• Dietary changes that emphasise whole grains, vegetables, fruits, and reduced intake of refined carbohydrates and saturated fats

Regarding pharmacological intervention, NICE does not routinely recommend medication for prediabetes. However, metformin may be considered in certain high-risk individuals when lifestyle interventions alone have been unsuccessful or are not feasible. This is an off-label use of metformin in the UK and requires informed consent. NICE suggests considering metformin particularly for those who:

• Have a BMI ≥35 kg/m² (or ≥30 kg/m² in South Asian and other high-risk groups)

• Are under 60 years of age

• Have a history of gestational diabetes

• Have additional risk factors such as family history or raised triglycerides

Metformin is the only medication with an evidence base for diabetes prevention in the UK context, supported by trials such as the Diabetes Prevention Program.

Rybelsus and other GLP-1 receptor agonists are not included in NICE guidance for prediabetes management. The NHS does not currently fund or recommend these medications for this indication. Patients with prediabetes (HbA1c 42–47 mmol/mol or FPG 5.5–6.9 mmol/L) should be referred to the NHS Diabetes Prevention Programme, which offers evidence-based behavioural interventions delivered by trained health professionals.

Alternative Options for Managing Prediabetes

For individuals diagnosed with prediabetes, a range of non-pharmacological and pharmacological strategies can help reduce the risk of progression to type 2 diabetes. The most effective and widely recommended approach is intensive lifestyle intervention, which has been shown in multiple large-scale trials (including the Diabetes Prevention Program and Finnish Diabetes Prevention Study) to reduce diabetes incidence by up to 58%.

Lifestyle modifications include:

• Weight loss: Achieving a 5–10% reduction in body weight can significantly improve insulin sensitivity and glycaemic control

• Dietary changes: Adopting a Mediterranean-style diet, reducing portion sizes, and limiting sugar-sweetened beverages and processed foods

• Increased physical activity: Combining aerobic exercise (such as brisk walking, cycling, or swimming) with resistance training to improve muscle glucose uptake

• Behavioural support: Participating in structured programmes like the NHS Diabetes Prevention Programme, which provides group-based education and coaching

For selected individuals at particularly high risk, metformin may be considered as an off-label treatment. This medication improves insulin sensitivity and has a well-established safety profile. However, it is not universally recommended and should be discussed with a GP, taking into account individual circumstances, contraindications (such as renal impairment), and potential side effects (commonly gastrointestinal upset).

For individuals with severe obesity, bariatric surgery may be considered according to NICE criteria (typically BMI ≥40 kg/m² or BMI 35–39.9 kg/m² with significant comorbidities). While prediabetes alone is not usually sufficient to meet these criteria, bariatric surgery has shown substantial benefits in diabetes prevention for eligible patients.

Continuous glucose monitoring is not routinely recommended or funded by the NHS for prediabetes management. Its use should be limited to research settings or specialist advice in specific circumstances.

It is essential that any treatment plan is personalised, evidence-based, and developed in partnership with healthcare professionals. NHS weight management services may provide additional structured support for those struggling with weight loss.

When to Speak to Your GP About Blood Sugar Levels

If you have been diagnosed with prediabetes or are concerned about your blood sugar levels, it is important to maintain regular contact with your general practitioner (GP) or practice nurse. Early identification and proactive management can significantly reduce the risk of developing type 2 diabetes and associated complications.

You should arrange to see your GP if you:

• Have been told you have prediabetes or borderline diabetes and have not received follow-up or lifestyle advice

• Experience symptoms that may indicate high blood sugar, such as increased thirst, frequent urination, unexplained weight loss, fatigue, or blurred vision

• Have risk factors for diabetes, including a family history, obesity (BMI ≥30 kg/m²), South Asian or African-Caribbean ethnicity, a history of gestational diabetes, or polycystic ovary syndrome (PCOS)

• Are struggling to achieve weight loss or lifestyle changes on your own and would benefit from structured support

• Have questions about medications such as metformin or other treatments you have read about, including Rybelsus

Seek urgent medical attention if you experience severe symptoms such as extreme thirst, frequent urination, rapid weight loss, vomiting, drowsiness, or confusion, which could indicate very high blood sugar or possible type 1 diabetes. Contact NHS 111 or 999 if you are acutely unwell.

Your GP can arrange appropriate investigations, including HbA1c testing to monitor your glycaemic status over time (though alternative tests may be needed if you have conditions affecting HbA1c reliability, such as pregnancy, certain anaemias, or kidney disease). They can refer you to the NHS Diabetes Prevention Programme if eligible, as well as to dietetic or weight management services. They can also assess cardiovascular risk factors (such as blood pressure and cholesterol) and provide holistic care.

Do not attempt to obtain or use Rybelsus or other prescription medications without medical supervision. These drugs are not licensed for prediabetes and may carry risks or side effects that need careful monitoring. If you experience any suspected side effects from medications, report them through the MHRA Yellow Card Scheme. Always discuss any concerns or treatment options with a qualified healthcare professional to ensure safe, evidence-based, and individualised care.

Frequently Asked Questions