Rybelsus (semaglutide) is an oral medication licensed in the UK for treating type 2 diabetes mellitus in adults. As a glucagon-like peptide-1 (GLP-1) receptor agonist, it works by stimulating insulin secretion, suppressing glucagon release, and slowing gastric emptying to improve blood glucose control. Whilst Rybelsus is not prescribed specifically to lower cholesterol, clinical trial data suggest it may have modest effects on certain lipid parameters as a secondary benefit. This article examines the evidence for cholesterol changes with Rybelsus, how it fits within comprehensive cardiovascular risk management, and when to discuss lipid concerns with your GP.

What Is Rybelsus and How Does It Work?

Rybelsus (semaglutide) is an oral medication licensed in the UK for the treatment of type 2 diabetes mellitus in adults. It can be used as monotherapy when metformin is inappropriate, or as an add-on therapy with other diabetes medications. It belongs to a class of medicines called glucagon-like peptide-1 (GLP-1) receptor agonists. Rybelsus is the first GLP-1 receptor agonist available in tablet form, offering an alternative to injectable formulations.

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

• Stimulating insulin secretion from pancreatic beta cells in a glucose-dependent manner, which helps lower blood sugar levels when they are elevated

• Suppressing glucagon release, thereby reducing glucose production by the liver

• Slowing gastric emptying, which prolongs the feeling of fullness and may contribute to weight loss

• Acting on appetite centres in the brain, leading to reduced calorie intake

Rybelsus follows a specific dosing schedule: starting at 3 mg once daily for 30 days, then increasing to 7 mg once daily. If additional glycaemic control is needed after at least 30 days, the dose may be increased to 14 mg once daily. The medication must be taken on an empty stomach with a small amount of water (up to 120 ml), at least 30 minutes before the first food, drink, or other oral medications of the day. Tablets should be swallowed whole and not split, crushed or chewed. If a dose is missed, skip that dose and take the next dose the following day.

According to NICE guidance (NG28), GLP-1 receptor agonists like Rybelsus may be considered when metformin is contraindicated or not tolerated, or as part of combination therapy when other treatments have not achieved adequate glycaemic control. They are particularly suitable for patients with a body mass index (BMI) of 35 kg/m² or higher (or lower if weight loss would benefit other obesity-related comorbidities). Treatment should be continued only if there is a reduction of at least 11 mmol/mol (1.0%) in HbA1c and 3% of initial body weight after 6 months.

Importantly, Rybelsus is not suitable for people with type 1 diabetes or diabetic ketoacidosis. There is an increased risk of hypoglycaemia when used with sulfonylureas or insulin. Patients should seek urgent medical attention for severe, persistent abdominal pain (which might indicate pancreatitis) and report any new or worsening vision problems.

Does Rybelsus Lower Cholesterol Levels?

There is no official indication for Rybelsus to lower cholesterol, and it is not licensed or prescribed specifically for dyslipidaemia management. However, clinical trial data suggest that semaglutide may have modest effects on certain lipid parameters as a secondary outcome.

In the PIONEER clinical trial programme, which evaluated oral semaglutide (Rybelsus) in people with type 2 diabetes, some participants experienced small reductions in total cholesterol and low-density lipoprotein cholesterol (LDL-C). These changes were generally modest, with reductions typically in the range of 2–5% from baseline values, though the exact magnitude varied across different studies and doses. The mechanism behind these lipid changes is not fully understood but may relate to:

• Weight loss associated with GLP-1 receptor agonist therapy, which can independently improve lipid profiles

• Improved insulin sensitivity and glucose metabolism

• Possible effects on hepatic lipid metabolism, though this remains hypothetical and an area of ongoing research

It is important to emphasise that any lipid-lowering effects observed with Rybelsus are secondary benefits rather than the primary therapeutic goal. Patients requiring cholesterol management should not rely on Rybelsus alone. According to NICE guidance (NG238), statins remain the first-line treatment for managing cardiovascular risk in people with type 2 diabetes, with additional agents such as ezetimibe or PCSK9 inhibitors considered when appropriate.

If you have both type 2 diabetes and high cholesterol, your GP will typically prescribe appropriate lipid-lowering therapy alongside your diabetes medication. While Rybelsus may improve certain cardiovascular risk factors such as weight and blood glucose control, it's important to note that cardiovascular outcome benefits have not been definitively established for the oral formulation of semaglutide.

Managing Cholesterol While Taking Rybelsus

If you are taking Rybelsus for type 2 diabetes and also have concerns about cholesterol, a comprehensive cardiovascular risk management approach is essential. People with diabetes receive an annual diabetes review which includes monitoring of lipid profiles, as they are at increased risk of cardiovascular disease.

Lifestyle modifications form the foundation of cholesterol management and work synergistically with Rybelsus:

• Dietary changes: Adopt a Mediterranean-style diet rich in fruits, vegetables, whole grains, oily fish, nuts, and olive oil whilst reducing saturated fat intake (found in red meat, butter, and processed foods)

• Physical activity: Aim for at least 150 minutes of moderate-intensity aerobic exercise weekly, which can raise HDL ("good") cholesterol and lower triglycerides

• Weight management: The weight loss often achieved with Rybelsus can independently improve lipid profiles

• Smoking cessation: Stopping smoking improves HDL cholesterol and reduces overall cardiovascular risk

• Alcohol moderation: Excessive alcohol consumption can raise triglyceride levels

Pharmacological management of cholesterol typically involves statins as first-line therapy for people with type 2 diabetes. In the UK, atorvastatin 20 mg is commonly prescribed for primary prevention, with higher intensity statin therapy (such as atorvastatin 40-80 mg) for secondary prevention. The goal is to achieve a reduction of at least 40% in non-HDL cholesterol, which should be checked 3 months after starting or intensifying statin therapy, and then at least annually.

Rybelsus can be safely taken alongside statins and other lipid-lowering medications with no clinically significant interactions. However, you should continue to take Rybelsus as directed (on an empty stomach, at least 30 minutes before other oral medicines). Regular blood tests will monitor both your HbA1c (long-term blood sugar control) and lipid profile to assess treatment effectiveness and guide any necessary adjustments to your medication regimen.

When to Speak with Your GP About Cholesterol and Rybelsus

Regular communication with your GP or diabetes care team is essential when managing both diabetes and cholesterol concerns. You should arrange a consultation if:

• You have not had a lipid profile check within the past 12 months as part of your annual diabetes review

• You experience new or worsening symptoms that might indicate cardiovascular problems, such as chest pain, unusual breathlessness, or leg pain when walking (claudication)

• You have a family history of premature cardiovascular disease or familial hypercholesterolaemia, which may require more intensive cholesterol management

• You are experiencing side effects from Rybelsus such as persistent nausea, vomiting, or abdominal pain (particularly if severe and persistent, which could indicate pancreatitis)

• You notice new or worsening vision problems, which should be promptly discussed with your healthcare team

• You experience symptoms of hypoglycaemia (particularly if taking Rybelsus alongside sulfonylureas or insulin)

• You wish to discuss whether your current cholesterol management is optimal or if additional treatments might be beneficial

Before starting Rybelsus, your GP should have assessed your overall cardiovascular risk profile, including cholesterol levels. People with type 2 diabetes are typically offered statin therapy regardless of their calculated risk score, though QRISK3 may be used to support discussions about treatment intensity.

Monitoring requirements while taking Rybelsus typically include:

• HbA1c measurements every 3–6 months to assess diabetes control

• Lipid profiles 3 months after starting or changing statin therapy to check for a reduction of at least 40% in non-HDL cholesterol, then at least annually

• Renal function tests (eGFR and urine albumin-to-creatinine ratio) as diabetes can affect kidney health

• Blood pressure checks at each appointment

If you are not achieving target cholesterol reductions with your current treatment, your GP may need to intensify lipid-lowering therapy. Never stop or adjust medications without medical advice, as both diabetes and cholesterol require consistent, long-term management to reduce cardiovascular risk effectively.

If you experience any suspected side effects from Rybelsus or other medications, these can be reported through the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk or via the Yellow Card app).

Frequently Asked Questions